Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Research Article

Synthesis and Characterization of Quinoline-3-Carboxamide Derivatives as Inhibitors of the ATM Kinase

Author(s): Srimadhavi Ravi, Sugata Barui, Sivapriya Kirubakaran*, Parul Duhan and Kaushik Bhowmik

Volume 20, Issue 23, 2020

Page: [2070 - 2079] Pages: 10

DOI: 10.2174/1568026620666200731174216

Price: $65

Abstract

Background: The importance of inhibiting the kinases of the DDR pathway for radiosensitizing cancer cells is well established. Cancer cells exploit these kinases for their survival, which leads to the development of resistance towards DNA damaging therapeutics.

Objective: In this article, the focus is on targeting the key mediator of the DDR pathway, the ATM kinase. A new set of quinoline-3-carboxamides, as potential inhibitors of ATM, is reported.

Methods: Quinoline-3-carboxamide derivatives were synthesized and cytotoxicity assay was performed to analyze the effect of molecules on different cancer cell lines like HCT116, MDA-MB-468, and MDA-MB-231.

Results: Three of the synthesized compounds showed promising cytotoxicity towards a selected set of cancer cell lines. Western Blot analysis was also performed by pre-treating the cells with quercetin, a known ATM upregulator, by causing DNA double-strand breaks. SAR studies suggested the importance of the electron-donating nature of the R group for the molecule to be toxic. Finally, Western-Blot analysis confirmed the down-regulation of ATM in the cells. Additionally, the PTEN negative cell line, MDA-MB-468, was more sensitive towards the compounds in comparison with the PTEN positive cell line, MDA-MB-231. Cytotoxicity studies against 293T cells showed that the compounds were at least three times less toxic when compared with HCT116.

Conclusion: In conclusion, these experiments will lay the groundwork for the evolution of potent and selective ATM inhibitors for the radio- and chemo-sensitization of cancer cells.

Keywords: DDR pathway, ATM kinase, Small molecule inhibitors, Quinoline derivatives, Cancer, Cytotoxicity.

Graphical Abstract

[1]
Cheung-Ong, K.; Giaever, G.; Nislow, C. DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology. Chem. Biol., 2013, 20(5), 648-659.
[http://dx.doi.org/10.1016/j.chembiol.2013.04.007] [PMID: 23706631]
[2]
Derheimer, F.A.; Kastan, M.B. Multiple roles of ATM in monitoring and maintaining DNA integrity. FEBS Lett., 2010, 584(17), 3675-3681.
[http://dx.doi.org/10.1016/j.febslet.2010.05.031] [PMID: 20580718]
[3]
Pike, K.G.; Barlaam, B.; Cadogan, E.; Campbell, A.; Chen, Y.; Colclough, N.; Davies, N.L.; De-Almeida, C.; Degorce, S.L.; Didelot, M.; Dishington, A.; Ducray, R.; Durant, S.T.; Hassall, L.A.; Holmes, J.; Hughes, G.D.; Macfaul, P.A.; Mulholland, K.R.; McGuire, T.M.; Ouvry, G.; Pass, M.; Robb, G.; Stratton, N.; Wang, Z.; Wilson, J.; Zhai, B.; Zhao, K.; Al-Huniti, N. The identification of potent, selective, and orally available inhibitors of ataxia telangiectasia mutated (atm) kinase: the discovery of azd0156 (8-6-[3-(dimethylamino)propoxy]pyridin-3-yl-3-methyl-1-(tetrahydro-2 h-pyran-4-yl)-1,3-dihydro-2 h-imidazo[4. J. Med. Chem., 2018, 61, 3823-3841.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01896] [PMID: 29683659]
[4]
Curtin, N.J. Inhibiting the DNA damage response as a therapeutic manoeuvre in cancer. Br. J. Pharmacol., 2013, 169(8), 1745-1765.
[http://dx.doi.org/10.1111/bph.12244] [PMID: 23682925]
[5]
Falck, J.; Coates, J.; Jackson, S.P. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature, 2005, 434(7033), 605-611.
[http://dx.doi.org/10.1038/nature03442] [PMID: 15758953]
[6]
Blackford, A.N.; Jackson, S.P. ATM, ATR, and DNA-PK: the trinity at the heart of the dna damage response. Mol. Cell, 2017, 66(6), 801-817.
[http://dx.doi.org/10.1016/j.molcel.2017.05.015] [PMID: 28622525]
[7]
Velic, D.; Couturier, A.M.; Ferreira, M.T.; Rodrigue, A.; Poirier, G.G.; Fleury, F.; Masson, J.Y. DNA Damage signalling and repair inhibitors: the long-sought-after achilles’ heel of cancer. Biomolecules, 2015, 5(4), 3204-3259.
[http://dx.doi.org/10.3390/biom5043204] [PMID: 26610585]
[8]
Begg, A.C.; Stewart, F.A.; Vens, C. Strategies to improve radiotherapy with targeted drugs. Nat. Rev. Cancer, 2011, 11(4), 239-253.
[http://dx.doi.org/10.1038/nrc3007] [PMID: 21430696]
[9]
Gavande, N.S.; VanderVere-Carozza, P.S.; Hinshaw, H.D.; Jalal, S.I.; Sears, C.R.; Pawelczak, K.S.; Turchi, J.J. DNA repair targeted therapy: The past or future of cancer treatment? Pharmacol. Ther., 2016, 160, 65-83.
[http://dx.doi.org/10.1016/j.pharmthera.2016.02.003] [PMID: 26896565]
[10]
Weber, A.M.; Ryan, A.J. ATM and ATR as therapeutic targets in cancer. Pharmacol. Ther., 2015, 149, 124-138.
[http://dx.doi.org/10.1016/j.pharmthera.2014.12.001] [PMID: 25512053]
[11]
Kurz, E.U.; Lees-Miller, S.P. DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair (Amst.), 2004, 3(8-9), 889-900.
[http://dx.doi.org/10.1016/j.dnarep.2004.03.029] [PMID: 15279774]
[12]
Guleria, A.; Chandna, S. ATM kinase: Much more than a DNA damage responsive protein. DNA Repair (Amst.), 2016, 39, 1-20.
[http://dx.doi.org/10.1016/j.dnarep.2015.12.009] [PMID: 26777338]
[13]
Ashwell, S.; Zabludoff, S. DNA damage detection and repair pathways--recent advances with inhibitors of checkpoint kinases in cancer therapy. Clin. Cancer Res., 2008, 14(13), 4032-4037.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-5138] [PMID: 18593978]
[14]
Cremona, C.A.; Behrens, A. ATM signalling and cancer. Oncogene, 2014, 33(26), 3351-3360.
[http://dx.doi.org/10.1038/onc.2013.275] [PMID: 23851492]
[15]
Min, J.; Guo, K.; Suryadevara, P.K.; Zhu, F.; Holbrook, G.; Chen, Y.; Feau, C.; Young, B.M.; Lemoff, A.; Connelly, M.C.; Kastan, M.B.; Guy, R.K. Optimization of a novel series of ataxia-telangiectasia mutated kinase inhibitors as potential radiosensitizing agents. J. Med. Chem., 2016, 59(2), 559-577.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01092] [PMID: 26632965]
[16]
McCabe, N.; Hanna, C.; Walker, S.M.; Gonda, D.; Li, J.; Wikstrom, K.; Savage, K.I.; Butterworth, K.T.; Chen, C.; Harkin, D.P.; Prise, K.M.; Kennedy, R.D. Mechanistic rationale to target pten-deficient tumor cells with inhibitors of the dna damage response kinase ATM. Cancer Res., 2015, 75(11), 2159-2165.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-3502] [PMID: 25870146]
[17]
Li, K.; Yan, H.; Guo, W.; Tang, M.; Zhao, X.; Tong, A.; Peng, Y.; Li, Q.; Yuan, Z. ATM inhibition induces synthetic lethality and enhances sensitivity of PTEN-deficient breast cancer cells to cisplatin. Exp. Cell Res., 2018, 366(1), 24-33.
[http://dx.doi.org/10.1016/j.yexcr.2018.03.006] [PMID: 29522753]
[18]
Chen, C-C.; Kass, E.M.; Yen, W-F.; Ludwig, T.; Moynahan, M.E.; Chaudhuri, J.; Jasin, M. ATM loss leads to synthetic lethality in BRCA1 BRCT mutant mice associated with exacerbated defects in homology-directed repair. Proc. Natl. Acad. Sci. USA, 2017, 114(29), 7665-7670.
[http://dx.doi.org/10.1073/pnas.1706392114] [PMID: 28659469]
[19]
Liu, Q.; Xu, C.; Kirubakaran, S.; Zhang, X.; Hur, W.; Liu, Y.; Kwiatkowski, N.P.; Wang, J.; Westover, K.D.; Gao, P.; Ercan, D.; Niepel, M.; Thoreen, C.C.; Kang, S.A.; Patricelli, M.P.; Wang, Y.; Tupper, T.; Altabef, A.; Kawamura, H.; Held, K.D.; Chou, D.M.; Elledge, S.J.; Janne, P.A.; Wong, K.K.; Sabatini, D.M.; Gray, N.S. Characterization of Torin2, an ATP-competitive inhibitor of mTOR, ATM, and ATR. Cancer Res., 2013, 73(8), 2574-2586.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-1702] [PMID: 23436801]
[20]
Durant, S.T.; Zheng, L.; Wang, Y.; Chen, K.; Zhang, L.; Zhang, T.; Yang, Z.; Riches, L.; Trinidad, A.G.; Fok, J.H.L.; Hunt, T.; Pike, K.G.; Wilson, J.; Smith, A.; Colclough, N.; Reddy, V.P.; Sykes, A.; Janefeldt, A.; Johnström, P.; Varnäs, K.; Takano, A.; Ling, S.; Orme, J.; Stott, J.; Roberts, C.; Barrett, I.; Jones, G.; Roudier, M.; Pierce, A.; Allen, J.; Kahn, J.; Sule, A.; Karlin, J.; Cronin, A.; Chapman, M.; Valerie, K.; Illingworth, R.; Pass, M. The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models. Sci. Adv.,, 2018, 4(6) eaat1719
[http://dx.doi.org/10.1126/sciadv.aat1719] [http://dx.doi.org/29938225]
[21]
Degorce, S.L.; Barlaam, B.; Cadogan, E.; Dishington, A.; Ducray, R.; Glossop, S.C.; Hassall, L.A.; Lach, F.; Lau, A.; McGuire, T.M.; Nowak, T.; Ouvry, G.; Pike, K.G.; Thomason, A.G. Discovery of novel 3-quinoline carboxamides as potent, selective, and orally bioavailable inhibitors of ataxia telangiectasia mutated (atm) kinase. J. Med. Chem., 2016, 59(13), 6281-6292.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00519] [PMID: 27259031]
[22]
Andersson, M.I.; MacGowan, A.P. Development of the quinolones. J. Antimicrob. Chemother., 2003, 51(Suppl. 1), 1-11.
[http://dx.doi.org/10.1093/jac/dkg212] [PMID: 12702698]
[23]
Afzal, O.; Kumar, S.; Haider, M.R.; Ali, M.R.; Kumar, R.; Jaggi, M.; Bawa, S. A review on anticancer potential of bioactive heterocycle quinoline. Eur. J. Med. Chem., 2015, 97, 871-910.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.044] [PMID: 25073919]
[24]
Ahmed, D.; Eide, P.W.; Eilertsen, I.A.; Danielsen, S.A.; Eknæs, M.; Hektoen, M.; Lind, G.E.; Lothe, R.A. Epigenetic and genetic features of 24 colon cancer cell lines. Oncogenesis, 2013, 2, e71.
[http://dx.doi.org/10.1038/oncsis.2013.35] [PMID: 24042735]
[25]
McCabe, N.; Walker, S.M.; Kennedy, R.D. When the guardian becomes the enemy: Targeting ATM in PTEN-deficient cancers. Mol. Cell. Oncol., 2015, 3(1), e1053595.
[http://dx.doi.org/10.1080/23723556.2015.1053595] [PMID: 27308567]
[26]
Hitomi, M.; Yang, K.; Stacey, A.W.; Stacey, D.W. Phosphorylation of cyclin D1 regulated by ATM or ATR controls cell cycle progression. Mol. Cell. Biol., 2008, 28(17), 5478-5493.
[http://dx.doi.org/10.1128/MCB.02047-07] [PMID: 18606783]
[27]
Janku, F.; Kaseb, A.O.; Tsimberidou, A.M.; Wolff, R.A.; Kurzrock, R. Identification of novel therapeutic targets in the PI3K/AKT/MTOR pathway in hepatocellular carcinoma using targeted next generation sequencing. Oncotarget, 2015, 5(10), 3012-3022.
[PMID: 24931142]
[28]
Ye, R.; Goodarzi, A.A.; Kurz, E.U.; Saito, S.; Higashimoto, Y.; Lavin, M.F.; Appella, E.; Anderson, C.W.; Lees-Miller, S.P. The isoflavonoids genistein and quercetin activate different stress signaling pathways as shown by analysis of site-specific phosphorylation of ATM, p53 and histone H2AX. DNA Repair (Amst.), 2004, 3(3), 235-244.
[http://dx.doi.org/10.1016/j.dnarep.2003.10.014] [PMID: 15177039]
[29]
O’Prey, J.; Brown, J.; Fleming, J.; Harrison, P.R. Effects of dietary flavonoids on major signal transduction pathways in human epithelial cells. Biochem. Pharmacol., 2003, 66(11), 2075-2088.
[http://dx.doi.org/10.1016/j.bcp.2003.07.007] [PMID: 14609732]
[30]
Liu, Q.; Wang, J.; Kang, S.A.; Thoreen, C.C.; Hur, W.; Ahmed, T.; Sabatini, D.M.; Gray, N.S. Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer. J. Med. Chem., 2011, 54(5), 1473-1480.
[http://dx.doi.org/10.1021/jm101520v] [PMID: 21322566]
[31]
Záletová, J.; Dzurilla, M.; Kutschy, P.; Pazdera, P.; Kováčik, V.; Aldölfi, J.; Bekešová, S. Synthesis of 4,6-Disubstituted-2-(1H-Indol-3-Yl). Benzothiazoles. Collect. Czechoslov. Chem. Commun., 2004, 69, 453-460.
[http://dx.doi.org/10.1135/cccc20040453]
[32]
Ghinet, A.; Moise, I.M.; Rigo, B.; Homerin, G.; Farce, A.; Dubois, J.; Bîcu, E. Studies on phenothiazines: New microtubule-interacting compounds with phenothiazine A-ring as potent antineoplastic agents. Bioorg. Med. Chem., 2016, 24(10), 2307-2317.
[http://dx.doi.org/10.1016/j.bmc.2016.04.001] [PMID: 27073050]
[33]
John, J.M.; Loorthuraja, R.; Antoniuk, E.; Bergens, S.H. Catalytic hydrogenation of functionalized amides under basic and neutral conditions. Catal. Sci. Technol., 2015, 5, 1181-1186.
[http://dx.doi.org/10.1039/C4CY01227E]
[34]
Carroll, T.X.; Thomas, T.D.; Bergersen, H.; Børve, K.J.; Saethre, L.J. Fluorine as a π donor. Carbon 1s photoelectron spectroscopy and proton affinities of fluorobenzenes. J. Org. Chem., 2006, 71(5), 1961-1968.
[http://dx.doi.org/10.1021/jo0523417] [PMID: 16496981]
[35]
Zannini, L.; Delia, D.; Buscemi, G. CHK2 kinase in the DNA damage response and beyond. J. Mol. Cell Biol., 2014, 6(6), 442-457.
[http://dx.doi.org/10.1093/jmcb/mju045] [PMID: 25404613]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version382msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[15:30:54] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[15:30:54] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[15:30:54] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (139ms)time
  • Application (243ms)time
  • 1 x Application (63.64%)
    243ms
    1 x Booting (36.36%)
    139ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    37 statements were executed, 4 of which were duplicates, 33 unique. Show only duplicated170ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('316567616','',1,1740497454,1740497454) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740497454
      1.03msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('316567616','/article/108790',1,1740497454,1740497454)
      220μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316567616 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316567616) limit 1
      11.43msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316567616
      • 1: 316567616
      • 2: 316567616
      • 3: 316567616
      • 4: 316567616
      • 5: 316567616
      • 6: 316567616
      • 7: 316567616
      • 8: 316567616
      • 9: 316567616
      • 10: 316567616
      • 11: 316567616
      • 12: 316567616
      • 13: 316567616
      • 14: 316567616
      • 15: 316567616
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=108790
      690μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 38 limit 1
      940μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 38
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=38) and sj.journal_id!=38 group by `j`.`nid`) as `aggregate_table`
      1.19msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=38) and sj.journal_id!=38 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.03msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=38) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.52msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=38) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.35msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '108790'
      950μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 108790
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '108790'
      2.89msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 108790
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '108790' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      3.55msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 108790
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      240μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      550μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 38 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      31.08msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 38 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      25.81msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 38 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      19.05msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 108790 limit 1
      240μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 108790
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 108790 and content_type = 'article' order by status desc limit 1
      270μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 16 and cd.sub_disease_id = 457 and content_id!=108790 and cd.content_type = 'article' order by rand() limit 20
      42.41msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 184452 limit 1
      220μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 184452
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      200μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CTMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      330μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CTMC
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '108790' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      340μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '10103' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      750μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '2703' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      390μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316567616 and j.to_ip >=316567616 )) and ((j.from_date <= 1740497454 and j.to_date >= 1740497454 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2703) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316567616 and j.to_ip >=316567616 )) and ((j.from_date <= 1740497454 and j.to_date >= 1740497454 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2703) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316567616 and j.to_ip >=316567616 )) and ((j.from_date <= 1740497454 and j.to_date >= 1740497454 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2703)
      11.7msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316567616 and j.to_ip >=316567616 )) and ((j.from_date <= 1740497454 and j.to_date >= 1740497454 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10103) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316567616 and j.to_ip >=316567616 )) and ((j.from_date <= 1740497454 and j.to_date >= 1740497454 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10103) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316567616 and j.to_ip >=316567616 )) and ((j.from_date <= 1740497454 and j.to_date >= 1740497454 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10103)
      850μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316567616 and j.to_ip >=316567616 )) and ((j.from_date <= 1740497454 and j.to_date >= 1740497454 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 108790) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316567616 and j.to_ip >=316567616 )) and ((j.from_date <= 1740497454 and j.to_date >= 1740497454 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 108790) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316567616 and j.to_ip >=316567616 )) and ((j.from_date <= 1740497454 and j.to_date >= 1740497454 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 108790)
      820μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '2070' and is_uploaded = 1 and issue_id = 10103 order by cast(first_page as SIGNED) desc limit 1
      600μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 2070
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '2079' and is_uploaded = 1 and issue_id = 10103 order by cast(first_page as SIGNED) asc limit 1
      540μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 2079
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      210μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      210μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 108790 limit 1
      3.47msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 108790
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 38 and `b`.`banner_from_date` <= 1740497454 and `b`.`banner_to_date` >= 1740497454 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.13msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 38
      • 3: 1740497454
      • 4: 1740497454
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 38 and `b`.`banner_from_date` <= 1740497454 and `b`.`banner_to_date` >= 1740497454 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.11msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 38
      • 3: 1740497454
      • 4: 1740497454
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='cda9da14d310bbf7038e3cd39ecbd5f6'
      200μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        mf8xprxOOrNOk2utf8I7ggTlUQJyZsdts9MzXx6E
        uc_cart_id
        cda9da14d310bbf7038e3cd39ecbd5f6
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/108790" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/108790
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6InFlN09kS05CK3pkV1ZiSys1dHFsMHc9PSIsInZhbHVlIjoiSHhjOUxFZVNjMTRqMTBZeVRKV2dOUEd6ZXNMbE9UVitGRlU3dVRGOHUzST0iLCJtYWMiOiJmNTNjMzdlYzE2Y2MyNjRkYTZiOGUwZWI0OTY0MDgwYTU4MDdlMTY1NjUwNzhkMDkxYWRhOGRhOTQzODVmZjNjIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6InFlN09kS05CK3pkV1ZiSys1dHFsMHc9PSIsInZhbHVlIjoiSHhjOUxFZVNjMTRqMTBZeVRKV2dOUEd6ZXNMbE9UVitGRlU3dVRGOHUzST0iLCJtYWMiOiJmNTNjMzdlYzE2Y2My" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 15:30:54 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkF2R1RjZUxnYjRKREQ4VytmU0RQVWc9PSIsInZhbHVlIjoid2Z1Nm52Zk5EWklFYitidktwU3Q4Zkx2THFvUlF4QXI2eEtaYk5HazhMS3hzalRSb25QT3hzek5OMEM2Rm85YVJrVUppREFFYXpaVVB4a2VCVG41U0Y2ZEM2NHZoTnRRbm1kRjRTaFU3ZldmUVhscXNRelB2UWZkcEFYcXFuSksiLCJtYWMiOiI0ODUyYTQyYTQ3ZmE2NzM4ZTllYjFmZDc3MTgzYjJiZDg0N2RlMzUxMTBlMWZlZDc0ZjhkYzcyNTVlZjZjYjUxIiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 03:30:54 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IkF2R1RjZUxnYjRKREQ4VytmU0RQVWc9PSIsInZhbHVlIjoid2Z1Nm52Zk5EWklFYitidktwU3Q4Zkx2THFvUlF4QXI2eEtaYk5HazhMS3hzalRSb25QT3hzek5OMEM2Rm85YVJrVUppR" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ijc5RjgrUldQK0poYXV1ZDRaOURsaVE9PSIsInZhbHVlIjoiUnB6SFB3NnlQalFtVVNDV2JvaWxReW84c1gwVHlnQnFNQzVOUE50QXdVQ0F4SVVqWWJpK01BZXJTMC9Ga2ZGQmVqYlA5Y2tsZjVBR3JsYXZLZTRnamRiUllRdW1XYkx5NjhXTWV4Y1NaN3dUZHN3ZFNOaGhXQjVhN2FUUHVaQUEiLCJtYWMiOiJjMTUzNDNjODk4OWFiYzdkZjAyMTRkYjQ5OWJmYWM0M2NmMDJhMjU3YzkyNzU3MjUyMGMwYzYzZjIyMjRkOTA3IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6Ijc5RjgrUldQK0poYXV1ZDRaOURsaVE9PSIsInZhbHVlIjoiUnB6SFB3NnlQalFtVVNDV2JvaWxReW84c1gwVHlnQnFNQzVOUE50QXdVQ0F4SVVqWWJpK01BZXJ" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkF2R1RjZUxnYjRKREQ4VytmU0RQVWc9PSIsInZhbHVlIjoid2Z1Nm52Zk5EWklFYitidktwU3Q4Zkx2THFvUlF4QXI2eEtaYk5HazhMS3hzalRSb25QT3hzek5OMEM2Rm85YVJrVUppREFFYXpaVVB4a2VCVG41U0Y2ZEM2NHZoTnRRbm1kRjRTaFU3ZldmUVhscXNRelB2UWZkcEFYcXFuSksiLCJtYWMiOiI0ODUyYTQyYTQ3ZmE2NzM4ZTllYjFmZDc3MTgzYjJiZDg0N2RlMzUxMTBlMWZlZDc0ZjhkYzcyNTVlZjZjYjUxIiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 03:30:54 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IkF2R1RjZUxnYjRKREQ4VytmU0RQVWc9PSIsInZhbHVlIjoid2Z1Nm52Zk5EWklFYitidktwU3Q4Zkx2THFvUlF4QXI2eEtaYk5HazhMS3hzalRSb25QT3hzek5OMEM2Rm85YVJrVUppR" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ijc5RjgrUldQK0poYXV1ZDRaOURsaVE9PSIsInZhbHVlIjoiUnB6SFB3NnlQalFtVVNDV2JvaWxReW84c1gwVHlnQnFNQzVOUE50QXdVQ0F4SVVqWWJpK01BZXJTMC9Ga2ZGQmVqYlA5Y2tsZjVBR3JsYXZLZTRnamRiUllRdW1XYkx5NjhXTWV4Y1NaN3dUZHN3ZFNOaGhXQjVhN2FUUHVaQUEiLCJtYWMiOiJjMTUzNDNjODk4OWFiYzdkZjAyMTRkYjQ5OWJmYWM0M2NmMDJhMjU3YzkyNzU3MjUyMGMwYzYzZjIyMjRkOTA3IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6Ijc5RjgrUldQK0poYXV1ZDRaOURsaVE9PSIsInZhbHVlIjoiUnB6SFB3NnlQalFtVVNDV2JvaWxReW84c1gwVHlnQnFNQzVOUE50QXdVQ0F4SVVqWWJpK01BZXJ" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "mf8xprxOOrNOk2utf8I7ggTlUQJyZsdts9MzXx6E" "uc_cart_id" => "cda9da14d310bbf7038e3cd39ecbd5f6" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/108790" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 15:30:54GET/article/108790314371