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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Mini-Review Article

Poly(ADP-Ribose) Polymerase-1 Inhibitors Drug Discovery, Design, and Development as Anticancer Agents from Past to Present: A Mini-Review

Author(s): Arwa AlGhamdi* and Hanine AlMubayedh

Volume 22, Issue 12, 2022

Published on: 13 January, 2022

Page: [1597 - 1606] Pages: 10

DOI: 10.2174/1389557521666210929144045

Price: $65

Abstract

Cancer treatments are known for their life-threatening toxicities attributed to their low selectivity; hence, new therapeutic approaches are being developed as alternatives. Among those approaches is the DNA repair mechanism, where its inhibition results selectively in the death of cancerous cells. Poly(ADP-Ribose) Polymerase (PARP) is one of the enzymes involved in the repair of damaged DNA. The inhibition of PARP shows to be a promising approach for effective targeted treatment of cancer, especially in tumours with pre-existing Homologous-Repair (HR) defects (i.e., BRCA). Nicotinamide, which is one of the PARP catalytic products, was the first identified PARP inhibitor (PARPi). The first FDA-approved PARPi was Olaparib in 2014 for the treatment of BRCA mutated advanced ovarian cancer. Several clinical trials have been conducted to further improve PARPi. However, there are some concerns related to drug resistance, PARPi sensitive-tumour identification, and toxic accumulation of PARPi. This report will review the uses of PARPi, drug design and development of PARPi from past to present, current issues, and prospective plans.

Keywords: Cancer, DNA repair, BRCA, poly(ADP-Ribose) polymerase (PARP), PARP inhibitors, olaparib.

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[1]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of inciden-ce and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Sikic, B.I. New approaches in cancer treatment. Ann. Oncol., 1999, 10(Suppl. 6), 149-153.
[http://dx.doi.org/10.1093/annonc/10.suppl_6.S149] [PMID: 10676567]
[3]
De Bont, R.; van Larebeke, N. Endogenous DNA damage in humans: A review of quantitative data. Mutagenesis, 2004, 19(3), 169-185.
[http://dx.doi.org/10.1093/mutage/geh025] [PMID: 15123782]
[4]
Amé, J-C.; Spenlehauer, C.; de Murcia, G. The PARP superfamily. BioEssays, 2004, 26(8), 882-893.
[http://dx.doi.org/10.1002/bies.20085] [PMID: 15273990]
[5]
Iyama, T.; Wilson, D.M. III DNA repair mechanisms in dividing and non-dividing cells. DNA Repair (Amst.), 2013, 12(8), 620-636.
[http://dx.doi.org/10.1016/j.dnarep.2013.04.015] [PMID: 23684800]
[6]
Roos, W.P.; Thomas, A.D.; Kaina, B. DNA damage and the balance between survival and death in cancer biology. Nat. Rev. Cancer, 2016, 16(1), 20-33.
[http://dx.doi.org/10.1038/nrc.2015.2] [PMID: 26678314]
[7]
Bouwman, P.; Jonkers, J. The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance. Nat. Rev. Cancer, 2012, 12(9), 587-598.
[http://dx.doi.org/10.1038/nrc3342] [PMID: 22918414]
[8]
Sancar, A.; Lindsey-Boltz, L.A.; Unsal-Kaçmaz, K.; Linn, S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu. Rev. Biochem., 2004, 73(1), 39-85.
[http://dx.doi.org/10.1146/annurev.biochem.73.011303.073723] [PMID: 15189136]
[9]
Chatterjee, N.; Walker, G.C. Mechanisms of DNA damage, repair, and mutagenesis. Environ. Mol. Mutagen., 2017, 58(5), 235-263.
[http://dx.doi.org/10.1002/em.22087] [PMID: 28485537]
[10]
Torgovnick, A.; Schumacher, B. DNA repair mechanisms in cancer development and therapy. Front. Genet., 2015, 6, 157.
[http://dx.doi.org/10.3389/fgene.2015.00157] [PMID: 25954303]
[11]
Ghosal, G.; Chen, J. DNA damage tolerance: A double-edged sword guarding the genome. Transl. Cancer Res., 2013, 2(3), 107-129.
[PMID: 24058901]
[12]
Wolters, S.; Schumacher, B. Genome maintenance and transcription integrity in aging and disease. Front. Genet., 2013, 4, 19.
[http://dx.doi.org/10.3389/fgene.2013.00019] [PMID: 23443494]
[13]
Fu, D.; Calvo, J.A.; Samson, L.D. Balancing repair and tolerance of DNA damage caused by alkylating agents. Nat. Rev. Cancer, 2012, 12(2), 104-120.
[http://dx.doi.org/10.1038/nrc3185] [PMID: 22237395]
[14]
Morales, J.; Li, L.; Fattah, F.J.; Dong, Y.; Bey, E.A.; Patel, M.; Gao, J.; Boothman, D.A. Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases. Crit. Rev. Eukaryot. Gene Expr., 2014, 24(1), 15-28.
[http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2013006875] [PMID: 24579667]
[15]
Kelley, M.R.; Logsdon, D.; Fishel, M.L. Targeting DNA repair pathways for cancer treatment: What’s new? Future Oncol., 2014, 10(7), 1215-1237.
[http://dx.doi.org/10.2217/fon.14.60] [PMID: 24947262]
[16]
Herceg, Z.; Wang, Z-Q. Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat. Res., 2001, 477(1-2), 97-110.
[http://dx.doi.org/10.1016/S0027-5107(01)00111-7] [PMID: 11376691]
[17]
Bernges, F.; Zeller, W.J. Combination effects of poly(ADP-ribose) polymerase inhibitors and DNA-damaging agents in ovarian tumor cell lines--with special reference to cisplatin. J. Cancer Res. Clin. Oncol., 1996, 122(11), 665-670.
[http://dx.doi.org/10.1007/BF01209029] [PMID: 8898976]
[18]
Smith, S. The world according to PARP. Trends Biochem. Sci., 2001, 26(3), 174-179.
[http://dx.doi.org/10.1016/S0968-0004(00)01780-1] [PMID: 11246023]
[19]
Bürkle, A. Physiology and pathophysiology of poly(ADP-ribosyl)ation. BioEssays, 2001, 23(9), 795-806.
[http://dx.doi.org/10.1002/bies.1115] [PMID: 11536292]
[20]
Budihardjo, I.; Oliver, H.; Lutter, M.; Luo, X.; Wang, X. Biochemical pathways of caspase activation during apoptosis. Annu. Rev. Cell Dev. Biol., 1999, 15(1), 269-290.
[http://dx.doi.org/10.1146/annurev.cellbio.15.1.269] [PMID: 10611963]
[21]
Lindahl, T.; Satoh, M.S.; Poirier, G.G.; Klungland, A. Post-translational modification of poly(ADP-ribose) polymerase induced by DNA strand breaks. Trends Biochem. Sci., 1995, 20(10), 405-411.
[http://dx.doi.org/10.1016/S0968-0004(00)89089-1] [PMID: 8533153]
[22]
Bernardi, R.; Rossi, L.; Poirier, G.G.; Scovassi, A.I. Analysis of poly(ADP-ribose) glycohydrolase activity in nuclear extracts from mam-malian cells. Biochim. Biophys. Acta, 1997, 1338(1), 60-68.
[http://dx.doi.org/10.1016/S0167-4838(96)00188-4] [PMID: 9074616]
[23]
Chambon, P.; Weill, J.D.; Mandel, P. Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme. Biochem. Biophys. Res. Commun., 1963, 11(1), 39-43.
[http://dx.doi.org/10.1016/0006-291X(63)90024-X] [PMID: 14019961]
[24]
Jacob, D.A.; Bahra, M.; Langrehr, J.M.; Boas-Knoop, S.; Stefaniak, R.; Davis, J.; Schumacher, G.; Lippert, S.; Neumann, U.P. Combination therapy of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide and gemcitabine shows strong antitumor activity in pancreatic can-cer cells. J. Gastroenterol. Hepatol., 2007, 22(5), 738-748.
[PMID: 17444865]
[25]
Curtin, N.J.; Szabo, C. Therapeutic applications of PARP inhibitors: Anticancer therapy and beyond. Mol. Aspects Med., 2013, 34(6), 1217-1256.
[http://dx.doi.org/10.1016/j.mam.2013.01.006] [PMID: 23370117]
[26]
Bryant, H.E.; Schultz, N.; Thomas, H.D.; Parker, K.M.; Flower, D.; Lopez, E.; Kyle, S.; Meuth, M.; Curtin, N.J.; Helleday, T. Specific ki-lling of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature, 2005, 434(7035), 913-917.
[http://dx.doi.org/10.1038/nature03443] [PMID: 15829966]
[27]
Ossovskaya, V.; Koo, I.C.; Kaldjian, E.P.; Alvares, C.; Sherman, B.M. Upregulation of poly (ADP-ribose) polymerase-1 (PARP1) in tri-ple-negative breast cancer and other primary Human tumor types. Genes Cancer, 2010, 1(8), 812-821.
[http://dx.doi.org/10.1177/1947601910383418] [PMID: 21779467]
[28]
Duncan, J.A.; Reeves, J.R.; Cooke, T.G. BRCA1 and BRCA2 proteins: Roles in health and disease. Mol. Pathol., 1998, 51(5), 237-247.
[http://dx.doi.org/10.1136/mp.51.5.237] [PMID: 10193517]
[29]
BRCA: The Breast Cancer Gene., Available from:. https://www.nationalbreastcancer.org/what-is-brca
[30]
Curtin, N. PARP inhibitors for anticancer therapy. Biochem. Soc. Trans., 2014, 42(1), 82-88.
[http://dx.doi.org/10.1042/BST20130187] [PMID: 24450632]
[31]
Farmer, H.; McCabe, N.; Lord, C.J.; Tutt, A.N.J.; Johnson, D.A.; Richardson, T.B.; Santarosa, M.; Dillon, K.J.; Hickson, I.; Knights, C.; Martin, N.M.B.; Jackson, S.P.; Smith, G.C.M.; Ashworth, A. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strate-gy. Nature, 2005, 434(7035), 917-921.
[http://dx.doi.org/10.1038/nature03445] [PMID: 15829967]
[32]
Roitt, I.M. The inhibition of carbohydrate metabolism in ascites-tumour cells by ethyleneimines. Biochem. J., 1956, 63(2), 300-307.
[http://dx.doi.org/10.1042/bj0630300] [PMID: 13328826]
[33]
Lu, Y.; Liu, Y.; Pang, Y.; Pacak, K.; Yang, C. Double-barreled gun: Combination of PARP inhibitor with conventional chemotherapy. Pharmacol. Ther., 2018, 188, 168-175.
[http://dx.doi.org/10.1016/j.pharmthera.2018.03.006] [PMID: 29621593]
[34]
Durkacz, B.W.; Omidiji, O.; Gray, D.A.; Shall, S. (ADP-ribose)n participates in DNA excision repair. Nature, 1980, 283(5747), 593-596.
[http://dx.doi.org/10.1038/283593a0] [PMID: 6243744]
[35]
Clark, J.B.; Ferris, G.M.; Pinder, S. Inhibition of nuclear NAD nucleosidase and poly ADP-ribose polymerase activity from rat liver by nicotinamide and 5′-methyl nicotinamide. Biochim. Biophys. Acta, 1971, 238(1), 82-85.
[http://dx.doi.org/10.1016/0005-2787(71)90012-8] [PMID: 4325158]
[36]
McLick, J.; Hakam, A.; Bauer, P.I.; Kun, E.; Zacharias, D.E.; Glusker, J.P. Benzamide-DNA interactions: deductions from binding, enzy-me kinetics and from X-ray structural analysis of a 9-ethyladenine-benzamide adduct. Biochim. Biophys. Acta, 1987, 909(1), 71-83.
[http://dx.doi.org/10.1016/0167-4781(87)90047-9] [PMID: 3107615]
[37]
Purnell, M.R.; Whish, W.J. Novel inhibitors of poly(ADP-ribose) synthetase. Biochem. J., 1980, 185(3), 775-777.
[http://dx.doi.org/10.1042/bj1850775] [PMID: 6248035]
[38]
Zaremba, T.; Curtin, N.J. PARP inhibitor development for systemic cancer targeting. Anticancer. Agents Med. Chem., 2007, 7(5), 515-523.
[http://dx.doi.org/10.2174/187152007781668715] [PMID: 17896912]
[39]
Milam, K.M.; Cleaver, J.E. Inhibitors of poly(adenosine diphosphate-ribose) synthesis: Effect on other metabolic processes. Science, 1984, 223(4636), 589-591.
[http://dx.doi.org/10.1126/science.6420886] [PMID: 6420886]
[40]
Malyuchenko, N.V.; Kotova, E.Y.; Kulaeva, O.I.; Kirpichnikov, M.P.; Studitskiy, V.M. PARP1 Inhibitors: Antitumor drug design. Acta Nat. (Engl. Ed.), 2015, 7(3), 27-37.
[http://dx.doi.org/10.32607/20758251-2015-7-3-27-37] [PMID: 26483957]
[41]
Banasik, M.; Komura, H.; Shimoyama, M.; Ueda, K. Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase. J. Biol. Chem., 1992, 267(3), 1569-1575.
[http://dx.doi.org/10.1016/S0021-9258(18)45983-2] [PMID: 1530940]
[42]
Jagtap, P.; Szabó, C. Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat. Rev. Drug Discov., 2005, 4(5), 421-440.
[http://dx.doi.org/10.1038/nrd1718] [PMID: 15864271]
[43]
Suto, M.J.; Turner, W.R.; Arundel-Suto, C.M.; Werbel, L.M.; Sebolt-Leopold, J.S. Dihydroisoquinolinones: The design and synthesis of a new series of potent inhibitors of poly(ADP-ribose) polymerase. Anticancer Drug Des., 1991, 6(2), 107-117.
[PMID: 1903948]
[44]
Cepeda, V.; Fuertes, M.A.; Castilla, J.; Alonso, C.; Quevedo, C.; Soto, M.; Pérez, J.M. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibi-tors in cancer chemotherapy. Rec. Pat. Anticancer Drug Discov., 2006, 1(1), 39-53.
[http://dx.doi.org/10.2174/157489206775246430] [PMID: 18221025]
[45]
White, A.W.; Almassy, R.; Calvert, A.H.; Curtin, N.J.; Griffin, R.J.; Hostomsky, Z.; Maegley, K.; Newell, D.R.; Srinivasan, S.; Golding, B.T. Resistance-modifying agents. 9. Synthesis and biological properties of benzimidazole inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase. J. Med. Chem., 2000, 43(22), 4084-4097.
[http://dx.doi.org/10.1021/jm000950v] [PMID: 11063605]
[46]
Langelier, M-F.; Zandarashvili, L.; Aguiar, P.M.; Black, B.E.; Pascal, J.M. NAD+ analog reveals PARP-1 substrate-blocking mechanism and allosteric communication from catalytic center to DNA-binding domains. Nat. Commun., 2018, 9(1), 844.
[http://dx.doi.org/10.1038/s41467-018-03234-8] [PMID: 29487285]
[47]
Hassa, P.O.; Hottiger, M.O. The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polyme-rases. Front. Biosci., 2008, 13(13), 3046-3082.
[http://dx.doi.org/10.2741/2909] [PMID: 17981777]
[48]
Ruf, A.; Rolli, V.; de Murcia, G.; Schulz, G.E. The mechanism of the elongation and branching reaction of poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesis. J. Mol. Biol., 1998, 278(1), 57-65.
[http://dx.doi.org/10.1006/jmbi.1998.1673] [PMID: 9571033]
[49]
Canan Koch, S.S.; Thoresen, L.H.; Tikhe, J.G.; Maegley, K.A.; Almassy, R.J.; Li, J.; Yu, X.H.; Zook, S.E.; Kumpf, R.A.; Zhang, C.; Bo-ritzki, T.J.; Mansour, R.N.; Zhang, K.E.; Ekker, A.; Calabrese, C.R.; Curtin, N.J.; Kyle, S.; Thomas, H.D.; Wang, L.Z.; Calvert, A.H.; Gol-ding, B.T.; Griffin, R.J.; Newell, D.R.; Webber, S.E.; Hostomsky, Z. Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis, and X-ray cocrystal structure. J. Med. Chem., 2002, 45(23), 4961-4974.
[50]
Skalitzky, D.J.; Marakovits, J.T.; Maegley, K.A.; Ekker, A.; Yu, X-H.; Hostomsky, Z.; Webber, S.E.; Eastman, B.W.; Almassy, R.; Li, J.; Curtin, N.J.; Newell, D.R.; Calvert, A.H.; Griffin, R.J.; Golding, B.T. Tricyclic benzimidazoles as potent poly(ADP-ribose) polymerase-1 inhibitors. J. Med. Chem., 2003, 46(2), 210-213.
[http://dx.doi.org/10.1021/jm0255769] [PMID: 12519059]
[51]
Tikhe, J.G.; Webber, S.E.; Hostomsky, Z.; Maegley, K.A.; Ekkers, A.; Li, J.; Yu, X-H.; Almassy, R.J.; Kumpf, R.A.; Boritzki, T.J.; Zhang, C.; Calabrese, C.R.; Curtin, N.J.; Kyle, S.; Thomas, H.D.; Wang, L-Z.; Calvert, A.H.; Golding, B.T.; Griffin, R.J.; Newell, D.R. Design, synthesis, and evaluation of 3,4-dihydro-2H-[1,4]diazepino[6,7,1-hi]indol-1-ones as inhibitors of poly(ADP-ribose) polymerase. J. Med. Chem., 2004, 47(22), 5467-5481.
[http://dx.doi.org/10.1021/jm030513r] [PMID: 15481984]
[52]
Calabrese, C.R.; Batey, M.A.; Thomas, H.D.; Durkacz, B.W.; Wang, L.Z.; Kyle, S.; Skalitzky, D.; Li, J.; Zhang, C.; Boritzki, T.; Maegley, K.; Calvert, A.H.; Hostomsky, Z.; Newell, D.R.; Curtin, N.J. Identification of potent nontoxic poly(ADP-Ribose) polymerase-1 inhibitors: Chemopotentiation and pharmacological studies. Clin. Cancer Res., 2003, 9(7), 2711-2718.
[PMID: 12855651]
[53]
Center for Drug Evaluation and Research FDA approves olaparib tablets for maintenance treatment in ovarian cancer. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-olaparib-tablets-maintenance-treatment-ovarian-cancer
[54]
Center for Drug Evaluation and Research. Rucaparib. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/rucaparib
[55]
Center for Drug Evaluation and Research. Niraparib (ZEJULA). Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/niraparib-zejula
[56]
Center for Drug Evaluation and Research FDA approves talazoparib for gBRCAm HER2-negative locally advanced or. Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-talazoparib-gbrcam-her2-negative-locally-advanced-or-metastatic-breast-cancer
[57]
Liang, H.; Tan, A.R. Iniparib, a PARP1 inhibitor for the potential treatment of cancer, including triple-negative breast cancer. IDrugs, 2010, 13(9), 646-656.
[58]
O’Shaughnessy, J.; Schwartzberg, L.; Danso, M.A.; Miller, K.D.; Rugo, H.S.; Neubauer, M.; Robert, N.; Hellerstedt, B.; Saleh, M.; Ri-chards, P.; Specht, J.M.; Yardley, D.A.; Carlson, R.W.; Finn, R.S.; Charpentier, E.; Garcia-Ribas, I.; Winer, E.P. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J. Clin. Oncol., 2014, 32(34), 3840-3847.
[http://dx.doi.org/10.1200/JCO.2014.55.2984] [PMID: 25349301]
[59]
Torsoli, A.; Serafino, P. Sanofi Ends Iniparib Research, Plans $285 Million Charge. Available from:. https://www.bloomberg.com/news/articles/2013-06-03/sanofi-ends-iniparib-research-plans-285-million-charge
[60]
Mersch, J.; Jackson, M.A.; Park, M.; Nebgen, D.; Peterson, S.K.; Singletary, C.; Arun, B.K.; Litton, J.K. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer, 2015, 121(2), 269-275.
[http://dx.doi.org/10.1002/cncr.29041] [PMID: 25224030]
[61]
Tutt, A.; Robson, M.; Garber, J.E.; Domchek, S.; Audeh, M.W.; Weitzel, J.N.; Friedlander, M.; Carmichael, J. Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer. J. Clin. Oncol., 2009, 27(18), CRA501.
[62]
Audeh, M.W.; Penson, R.T.; Friedlander, M.; Powell, B.; Bell-McGuinn, K.M.; Scott, C.; Weitzel, J.N.; Carmichael, J.; Tutt, A. Phase II trial of the oral PARP inhibitor olaparib (AZD2281) in BRCA-deficient advanced ovarian cancer. J. Clin. Oncol., 2009, 27(15), 5500.
[63]
van de Ven, A.L.; Tangutoori, S.; Baldwin, P.; Qiao, J.; Gharagouzloo, C.; Seitzer, N.; Clohessy, J.G.; Makrigiorgos, G.M.; Cormack, R.; Pandolfi, P.P.; Sridhar, S. Nanoformulation of olaparib amplifies PARP inhibition and sensitizes PTEN/TP53-deficient prostate cancer to radiation. Mol. Cancer Ther., 2017, 16(7), 1279-1289.
[http://dx.doi.org/10.1158/1535-7163.MCT-16-0740] [PMID: 28500233]
[64]
Noordermeer, S.M.; van Attikum, H. PARP inhibitor resistance: A tug-of-War in BRCA-mutated cells. Trends Cell Biol., 2019, 29(10), 820-834.
[http://dx.doi.org/10.1016/j.tcb.2019.07.008] [PMID: 31421928]

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