Abstract
Heat shock protein 90 (Hsp90) is a chaperone protein that prevents many other proteins from aggregating by folding them in a certain way. Hsp90 consists of three structural domains: N-terminal, middle and C-terminal domains. Hsp90 has many activities in numerous proteins and signaling pathways like chimeric fusion proteins, steroid hormone receptors, tumor suppressor genes, and cell cycle regulatory proteins. The role of Hsp90 is not only in cancer but also in other diseases like COVID-19, leishmaniasis, diabetes, flavi virus, systemic sclerosis, grass carp reovirus, psoriasis, malaria, cardiac fibrosis, and alcohol-related liver diseases. This review is a compilation of the pharmacological profile of Hsp90 inhibitors, problems associated with them, and suggested remedies for the same.
Keywords: Hsp90, chaperones, cancer, proteosome, geldanamycin, radicicol.
[http://dx.doi.org/10.1007/978-94-007-5943-5]
[http://dx.doi.org/10.1186/1471-2164-7-156] [PMID: 16780600]
[http://dx.doi.org/10.1038/nrc1716] [PMID: 16175177]
[http://dx.doi.org/10.1186/1750-1326-5-24] [PMID: 20525284]
[http://dx.doi.org/10.1016/j.bbamcr.2011.11.007] [PMID: 22154817]
[http://dx.doi.org/10.4103/2319-4170.113230] [PMID: 23806880]
[http://dx.doi.org/10.1038/nature04716] [PMID: 16625188]
[http://dx.doi.org/10.1083/jcb.143.4.901] [PMID: 9817749]
[http://dx.doi.org/10.1038/emboj.2008.190] [PMID: 18818696]
[http://dx.doi.org/10.1038/nsmb.2045] [PMID: 21460846]
[http://dx.doi.org/10.1038/sj.emboj.7600060] [PMID: 14739935]
[http://dx.doi.org/10.1016/j.molcel.2006.07.016] [PMID: 16949366]
[http://dx.doi.org/10.1016/j.molcel.2011.01.029] [PMID: 21474071]
[http://dx.doi.org/10.1016/S0014-5793(97)01363-X] [PMID: 9414113]
[http://dx.doi.org/10.1073/pnas.95.4.1495] [PMID: 9465043]
[http://dx.doi.org/10.1016/j.str.2004.03.020] [PMID: 15274928]
[http://dx.doi.org/10.1038/nsmb.2114] [PMID: 21892170]
[http://dx.doi.org/10.1021/ct100334n] [PMID: 26616092]
[http://dx.doi.org/10.1074/jbc.M111874200] [PMID: 11805114]
[http://dx.doi.org/10.1016/S0968-0004(97)01005-0] [PMID: 9066258]
[http://dx.doi.org/10.1128/MCB.19.6.4535] [PMID: 10330192]
[http://dx.doi.org/10.1016/j.molcel.2005.09.023] [PMID: 16307917]
[http://dx.doi.org/10.1016/S0092-8674(00)80830-2] [PMID: 10786835]
[http://dx.doi.org/10.1074/jbc.M109.031658] [PMID: 19553666]
[http://dx.doi.org/10.1038/nrm1492] [PMID: 15459659]
[http://dx.doi.org/10.1146/annurev.biochem.75.103004.142738] [PMID: 16756493]
[http://dx.doi.org/10.1128/EC.1.6.936-943.2002] [PMID: 12477794]
[http://dx.doi.org/10.1073/pnas.1000916107] [PMID: 20736353]
[http://dx.doi.org/10.1007/s10858-006-9030-0] [PMID: 16821127]
[http://dx.doi.org/10.1002/cbic.200300658] [PMID: 12964162]
[http://dx.doi.org/10.1074/jbc.M601759200] [PMID: 16565516]
[http://dx.doi.org/10.1016/j.molcel.2007.08.024] [PMID: 17936703]
[PMID: 11280726]
[http://dx.doi.org/10.1124/mol.104.007831] [PMID: 15625278]
[http://dx.doi.org/10.1016/S0960-0760(00)00037-6] [PMID: 10822011]
[http://dx.doi.org/10.1210/endo.141.12.7836] [PMID: 11108261]
[http://dx.doi.org/10.1128/MCB.18.3.1517] [PMID: 9488468]
[http://dx.doi.org/10.1038/35106065] [PMID: 11902577]
[PMID: 10919672]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-2966] [PMID: 17363512]
[http://dx.doi.org/10.1002/path.2795] [PMID: 21125667]
[http://dx.doi.org/10.1007/s12079-011-0121-7] [PMID: 21484190]
[http://dx.doi.org/10.1016/j.bbrc.2011.10.054] [PMID: 22027149]
[PMID: 21931937]
[http://dx.doi.org/10.1038/nrclinonc.2010.136] [PMID: 20859283]
[PMID: 12810654]
[http://dx.doi.org/10.1007/s10637-009-9381-y] [PMID: 20082116]
[PMID: 12579931]
[http://dx.doi.org/10.1002/ijc.20611] [PMID: 15455381]
[http://dx.doi.org/10.1074/jbc.M006192200] [PMID: 11007781]
[http://dx.doi.org/10.1016/S1074-5521(01)00015-1] [PMID: 11306353]
[http://dx.doi.org/10.1021/cc010017t] [PMID: 11703144]
[http://dx.doi.org/10.1038/386414a0] [PMID: 9121560]
[http://dx.doi.org/10.1016/S0968-0896(02)00253-5] [PMID: 12213470]
[http://dx.doi.org/10.1007/s11010-006-0638-x] [PMID: 16328963]
[http://dx.doi.org/10.1111/j.1365-2141.2010.08265.x] [PMID: 20618337]
[http://dx.doi.org/10.1007/s00280-004-0865-3] [PMID: 15338192]
[http://dx.doi.org/10.1111/j.1442-2042.2010.02450.x] [PMID: 20409220]
[http://dx.doi.org/10.7164/antibiotics.23.442] [PMID: 5459626]
[PMID: 1551101]
[http://dx.doi.org/10.2174/156802606777812031] [PMID: 16842154]
[http://dx.doi.org/10.1007/s10637-010-9493-4] [PMID: 20683637]
[http://dx.doi.org/10.1158/1078-0432.CCR-09-2882] [PMID: 20682705]
[http://dx.doi.org/10.4161/cbt.7.10.6585] [PMID: 18769124]
[http://dx.doi.org/10.1158/1078-0432.CCR-10-0503] [PMID: 20525756]
[http://dx.doi.org/10.1200/jco.2008.26.15_suppl.1027]
[http://dx.doi.org/10.1016/j.tetlet.2006.01.116]
[http://dx.doi.org/10.1007/s002800100373] [PMID: 11800023]
[http://dx.doi.org/10.1038/nature01913] [PMID: 14508491]
[http://dx.doi.org/10.1021/jm0508078] [PMID: 16392823]
[http://dx.doi.org/10.1021/acs.biochem.9b00781] [PMID: 31592648]
[http://dx.doi.org/10.1038/s41467-018-04343-0] [PMID: 29760386]
[http://dx.doi.org/10.1021/jacs.8b11747] [PMID: 30592612]
[http://dx.doi.org/10.1016/j.bmc.2011.03.013] [PMID: 21459002]
[http://dx.doi.org/10.1146/annurev-biochem-060713-035708] [PMID: 24905785]
[http://dx.doi.org/10.1021/jm400619b] [PMID: 23965125]
[http://dx.doi.org/10.1038/nchembio.1335] [PMID: 23995768]
[http://dx.doi.org/10.1002/ptr.2159] [PMID: 17450509]
[http://dx.doi.org/10.1021/jm8007486] [PMID: 18816111]
[http://dx.doi.org/10.1101/2020.04.03.024257]
[http://dx.doi.org/10.3389/fmicb.2014.00296] [PMID: 24987391]
[http://dx.doi.org/10.1016/j.virol.2015.08.010] [PMID: 26331680]
[http://dx.doi.org/10.1016/j.isci.2021.102151] [PMID: 33585804]
[http://dx.doi.org/10.1128/MCB.22.24.8506-8513.2002] [PMID: 12446770]
[http://dx.doi.org/10.21203/rs.3.rs-18714/v1]
[http://dx.doi.org/10.1165/rcmb.2007-0324OC] [PMID: 18474672]
[http://dx.doi.org/10.1007/978-1-4939-1130-1_17]
[http://dx.doi.org/10.1038/nrm.2017.20] [PMID: 28429788]
[http://dx.doi.org/10.1074/jbc.M110.155317] [PMID: 20837488]
[http://dx.doi.org/10.1038/sj.bjp.0706396] [PMID: 16170327]
[http://dx.doi.org/10.1016/j.febslet.2007.05.040] [PMID: 17559840]
[http://dx.doi.org/10.1016/j.bmcl.2014.12.048] [PMID: 25547934]
[http://dx.doi.org/10.2174/15748928113089990031] [PMID: 23312026]
[http://dx.doi.org/10.1042/bj3100225] [PMID: 7646449]
[http://dx.doi.org/10.1091/mbc.12.11.3307] [PMID: 11694568]
[http://dx.doi.org/10.1007/s004300100074] [PMID: 11770104]
[http://dx.doi.org/10.2174/092986611794475002] [PMID: 20955165]
[http://dx.doi.org/10.1080/14756366.2020.1726342] [PMID: 32048531]
[http://dx.doi.org/10.1016/j.immuni.2011.05.003] [PMID: 21616437]
[http://dx.doi.org/10.1371/journal.ppat.1000757] [PMID: 20140199]
[http://dx.doi.org/10.1038/nri3581] [PMID: 24362405]
[http://dx.doi.org/10.3390/cells9040899] [PMID: 32272626]
[http://dx.doi.org/10.1021/acs.jproteome.9b00318] [PMID: 31199156]
[http://dx.doi.org/10.3390/ijms18050954] [PMID: 28468311]
[http://dx.doi.org/10.1074/mcp.M114.038984] [PMID: 24855065]
[http://dx.doi.org/10.1038/s41598-018-22639-5] [PMID: 29523827]
[http://dx.doi.org/10.1016/j.antiviral.2019.104590] [PMID: 31421166]
[http://dx.doi.org/10.1038/s41467-020-15735-6] [PMID: 32312964]
[http://dx.doi.org/10.21203/rs.3.rs-1232310/v1]
[http://dx.doi.org/10.1038/s41396-019-0519-4] [PMID: 31664159]
[http://dx.doi.org/10.1038/s41598-020-79139-8] [PMID: 33414495]
[http://dx.doi.org/10.1038/ni.2479] [PMID: 23202271]
[http://dx.doi.org/10.1111/exd.14302] [PMID: 33583094]
[http://dx.doi.org/10.1039/C9OB01264H] [PMID: 31263819]
[http://dx.doi.org/10.1074/jbc.M305214200] [PMID: 12855682]
[http://dx.doi.org/10.1096/fj.10-180554] [PMID: 21357526]
[http://dx.doi.org/10.1111/bph.15626] [PMID: 34265086]
[http://dx.doi.org/10.1002/cphy.c140078] [PMID: 26426467]
[http://dx.doi.org/10.1016/j.jhep.2004.11.033] [PMID: 15710220]
[http://dx.doi.org/10.1016/j.jhep.2021.02.028] [PMID: 33675874]
[http://dx.doi.org/10.1161/01.RES.0000124979.46214.E3] [PMID: 15001530]
[http://dx.doi.org/10.1136/bmjdrc-2021-002579] [PMID: 35091448]