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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Mini-Review Article

CDK酶抑制剂在癌症治疗中的应用综述

卷 23, 期 8, 2023

发表于: 03 May, 2023

页: [603 - 619] 页: 17

弟呕挨: 10.2174/1568009623666230320144713

价格: $65

摘要

在癌症治疗中处理细胞周期的能力带来了新的药物开发的可能性。周期蛋白依赖性激酶是一组控制细胞周期进程的蛋白质。当特定CDK位点被磷酸化时，CDK/细胞周期蛋白复合物被激活。由于它们的非选择性和严重的毒性，大多数第一代CDK抑制剂(也称为泛CDK抑制剂)尚未被批准用于临床。尽管如此，在允许泛cdk抑制剂在临床环境中使用方面已经取得了重大进展。近年来，由于联合治疗技术的引入，泛cdk抑制剂的毒副作用已经降低。因此，泛cdk抑制剂作为一种联合治疗方法重新获得了许多临床潜力。本文介绍了CDK家族成员，并讨论了它们在细胞周期控制中的重要作用。然后，我们描述了CDK抑制剂的研究现状，重点是CDK4/6以外的抑制剂。我们根据第一代泛CDKIs的研究阶段、临床试验和肿瘤靶向性，分别提到了黄吡醇和罗斯科维汀，以及第二代泛CDKIs的dinaciclib、P276-00、AT7519、TG02、roniclib和RGB-286638。CDKIs是CDK4/6、CDK7、CDK9和CDK12抑制剂。最后，我们研究了CDK抑制剂和PD1/PDL1抗体一起使用时的疗效，这可能会导致一种可行的癌症治疗策略的发展。

关键词: 细胞周期蛋白，CDK，基因表达，细胞周期调控，癌症，抑制。

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图形摘要

[1]
Garrett, M.D.; Fattaey, A. CDK inhibition and cancer therapy. Curr. Opin. Genet. Dev., 1999, 9(1), 104-111.
[http://dx.doi.org/10.1016/S0959-437X(99)80015-X] [PMID: 10072351]
[2]
Arellano, M.; Moreno, S. Regulation of CDK/cyclin complexes during the cell cycle. Int. J. Biochem. Cell Biol., 1997, 29(4), 559-573.
[http://dx.doi.org/10.1016/S1357-2725(96)00178-1] [PMID: 9363633]
[3]
Patel, V.; Senderowicz, A.M.; Pinto, D., Jr; Igishi, T.; Raffeld, M.; Quintanilla-Martinez, L.; Ensley, J.F.; Sausville, E.A.; Gutkind, J.S. Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis. J. Clin. Invest., 1998, 102(9), 1674-1681.
[http://dx.doi.org/10.1172/JCI3661] [PMID: 9802881]
[4]
Aklilu, M.; Kindler, H.L.; Donehower, R.C.; Mani, S.; Vokes, E.E. Phase II study of flavopiridol in patients with advanced colorectal cancer. Ann. Oncol., 2003, 14(8), 1270-1273.
[http://dx.doi.org/10.1093/annonc/mdg343] [PMID: 12881391]
[5]
Olgen, S. Overview on anticancer drug design and development. Curr. Med. Chem., 2018, 25(15), 1704-1719.
[http://dx.doi.org/10.2174/0929867325666171129215610] [PMID: 29189124]
[6]
Ivanchuk, S.M.; Rutka, J.T. Regulation of the cell cycle and interventional developmental therapeutics. In: Handbook of brain tumor chemotherapy; Academic Press, 2006; pp. 123-140.
[http://dx.doi.org/10.1016/B978-012088410-0/50047-0]
[7]
Whalen, K. Lippincott® Illustrated Reviews: Pharmacology; Wolters Kluwer: India, 2018.
[8]
Malumbres, M.; Barbacid, M. Mammalian cyclin-dependent kinases. Trends Biochem. Sci., 2005, 30(11), 630-641.
[http://dx.doi.org/10.1016/j.tibs.2005.09.005] [PMID: 16236519]
[9]
Colas, P.; Cohen, B.; Jessen, T.; Grishina, I.; McCoy, J.; Brent, R. Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2. Nature, 1996, 380(6574), 548-550.
[http://dx.doi.org/10.1038/380548a0] [PMID: 8606778]
[10]
Johnson, N.; Shapiro, G.I. Cyclin-dependent kinase 4/6 inhibition in cancer therapy. Cell Cycle, 2012, 11(21), 3913.
[http://dx.doi.org/10.4161/cc.22390] [PMID: 23032266]
[11]
Mayer, E.L. Targeting breast cancer with CDK inhibitors. Curr. Oncol. Rep., 2015, 17(5), 20.
[http://dx.doi.org/10.1007/s11912-015-0443-3] [PMID: 25716100]
[12]
Bergqvist, J.; Elmberger, G.; Ohd, J.; Linderholm, B.; Bjohle, J.; Hellborg, H.; Nordgren, H.; Borg, A.L.; Skoog, L.; Bergh, J. Activated ERK1/2 and phosphorylated oestrogen receptor α are associated with improved breast cancer survival in women treated with tamoxifen. Eur. J. Cancer, 2006, 42(8), 1104-1112.
[http://dx.doi.org/10.1016/j.ejca.2006.01.028] [PMID: 16603346]
[13]
Park, D.S.; Levine, B.; Ferrari, G.; Greene, L.A. Cyclin dependent kinase inhibitors and dominant negative cyclin dependent kinase 4 and 6 promote survival of NGF-deprived sympathetic neurons. J. Neurosci., 1997, 17(23), 8975-8983.
[http://dx.doi.org/10.1523/JNEUROSCI.17-23-08975.1997] [PMID: 9364045]
[14]
Peyressatre, M.; Prével, C.; Pellerano, M.; Morris, M. Targeting cyclin-dependent kinases in human cancers: From small molecules to Peptide inhibitors. Cancers, 2015, 7(1), 179-237.
[http://dx.doi.org/10.3390/cancers7010179] [PMID: 25625291]
[15]
Malumbres, M. Cyclin-dependent kinases. Genome Biol., 2014, 15(6), 122.
[http://dx.doi.org/10.1186/gb4184] [PMID: 25180339]
[16]
Knockaert, M.; Greengard, P.; Meijer, L. Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol. Sci., 2002, 23(9), 417-425.
[http://dx.doi.org/10.1016/S0165-6147(02)02071-0] [PMID: 12237154]
[17]
Pines, J. Cyclins and cyclin-dependent kinases: A biochemical view. Biochem. J., 1995, 308(3), 697-711.
[http://dx.doi.org/10.1042/bj3080697] [PMID: 8948422]
[18]
Sánchez-Martínez, C.; Gelbert, L.M.; Lallena, M.J.; de Dios, A. Cyclin dependent kinase (CDK) inhibitors as anticancer drugs. Bioorg. Med. Chem. Lett., 2015, 25(17), 3420-3435.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.100] [PMID: 26115571]
[19]
Fry, D.W.; Harvey, P.J.; Keller, P.R.; Elliott, W.L.; Meade, M.; Trachet, E.; Albassam, M.; Zheng, X.; Leopold, W.R.; Pryer, N.K.; Toogood, P.L. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol. Cancer Ther., 2004, 3(11), 1427-1438.
[http://dx.doi.org/10.1158/1535-7163.1427.3.11] [PMID: 15542782]
[20]
Spring, L.M.; Wander, S.A.; Zangardi, M.; Bardia, A. CDK 4/6 inhibitors in breast cancer: Current controversies and future directions. Curr. Oncol. Rep., 2019, 21(3), 25.
[http://dx.doi.org/10.1007/s11912-019-0769-3] [PMID: 30806829]
[21]
Long, F.; He, Y.; Fu, H.; Li, Y.; Bao, X.; Wang, Q.; Wang, Y.; Xie, C.; Lou, L. Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, in vitro and in human tumor xenograft models. Cancer Sci., 2019, 110(4), 1420-1430.
[http://dx.doi.org/10.1111/cas.13957] [PMID: 30724426]
[22]
Besson, A.; Dowdy, S.F.; Roberts, J.M. CDK inhibitors: Cell cycle regulators and beyond. Dev. Cell, 2008, 14(2), 159-169.
[http://dx.doi.org/10.1016/j.devcel.2008.01.013] [PMID: 18267085]
[23]
Malumbres, M.; Pevarello, P.; Barbacid, M.; Bischoff, J.R. CDK inhibitors in cancer therapy: what is next? Trends Pharmacol. Sci., 2008, 29(1), 16-21.
[http://dx.doi.org/10.1016/j.tips.2007.10.012] [PMID: 18054800]
[24]
Senderowicz, A.M. Small-molecule cyclin-dependent kinase modulators. Oncogene, 2003, 22(42), 6609-6620.
[http://dx.doi.org/10.1038/sj.onc.1206954] [PMID: 14528286]
[25]
Schwartz, G.K. CDK inhibitors: Cell cycle arrest versus apoptosis. Cell Cycle, 2002, 1(2), 113-114.
[http://dx.doi.org/10.4161/cc.1.2.112] [PMID: 12429920]
[26]
Arris, C.E.; Boyle, F.T.; Calvert, A.H.; Curtin, N.J.; Endicott, J.A.; Garman, E.F.; Gibson, A.E.; Golding, B.T.; Grant, S.; Griffin, R.J.; Jewsbury, P.; Johnson, L.N.; Lawrie, A.M.; Newell, D.R.; Noble, M.E.M.; Sausville, E.A.; Schultz, R.; Yu, W. Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles. J. Med. Chem., 2000, 43(15), 2797-2804.
[http://dx.doi.org/10.1021/jm990628o] [PMID: 10956187]
[27]
Berkofsky-Fessler, W.; Nguyen, T.Q.; Delmar, P.; Molnos, J.; Kanwal, C.; DePinto, W.; Rosinski, J.; McLoughlin, P.; Ritland, S.; DeMario, M.; Tobon, K.; Reidhaar-Olson, J.F.; Rueger, R.; Hilton, H. Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients. Mol. Cancer Ther., 2009, 8(9), 2517-2525.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0083] [PMID: 19755512]
[28]
Cicenas, J.; Valius, M. The CDK inhibitors in cancer research and therapy. J. Cancer Res. Clin. Oncol., 2011, 137(10), 1409-1418.
[http://dx.doi.org/10.1007/s00432-011-1039-4] [PMID: 21877198]
[29]
Zhang, M.; Zhang, L.; Hei, R.; Li, X.; Cai, H.; Wu, X.; Zheng, Q.; Cai, C. CDK inhibitors in cancer therapy, an overview of recent development. Am. J. Cancer Res., 2021, 11(5), 1913-1935.
[PMID: 34094661]
[30]
Meijer, L.; Borgne, A.; Mulner, O.; Chong, J.P.J.; Blow, J.J.; Inagaki, N.; Inagaki, M.; Delcros, J.G.; Moulinoux, J.P. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur. J. Biochem., 1997, 243(1-2), 527-536.
[http://dx.doi.org/10.1111/j.1432-1033.1997.t01-2-00527.x] [PMID: 9030781]
[31]
Cicenas, J.; Kalyan, K.; Sorokinas, A.; Stankunas, E.; Levy, J.; Meskinyte, I.; Stankevicius, V.; Kaupinis, A.; Valius, M. Roscovitine in cancer and other diseases. Ann. Transl. Med., 2015, 3(10), 135.
[http://dx.doi.org/10.3978/j.issn.2305-5839.2015.03.61] [PMID: 26207228]
[32]
Whittaker, S.R.; Mallinger, A.; Workman, P.; Clarke, P.A. Inhibitors of cyclin-dependent kinases as cancer therapeutics. Pharmacol. Ther., 2017, 173, 83-105.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.008] [PMID: 28174091]
[33]
Asghar, U.; Witkiewicz, A.K.; Turner, N.C.; Knudsen, E.S. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat. Rev. Drug Discov., 2015, 14(2), 130-146.
[http://dx.doi.org/10.1038/nrd4504] [PMID: 25633797]
[34]
Zeidner, J.F.; Karp, J.E. Clinical activity of alvocidib (flavopiridol) in acute myeloid leukemia. Leuk. Res., 2015, 39(12), 1312-1318.
[http://dx.doi.org/10.1016/j.leukres.2015.10.010] [PMID: 26521988]
[35]
Parker, B.W.; Kaur, G.; Nieves-Neira, W.; Taimi, M.; Kohlhagen, G.; Shimizu, T.; Losiewicz, M.D.; Pommier, Y.; Sausville, E.A.; Senderowicz, A.M. Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol. Blood, 1998, 91(2), 458-465.
[http://dx.doi.org/10.1182/blood.V91.2.458] [PMID: 9427698]
[36]
Phelps, M.A.; Lin, T.S.; Johnson, A.J.; Hurh, E.; Rozewski, D.M.; Farley, K.L.; Wu, D.; Blum, K.A.; Fischer, B.; Mitchell, S.M.; Moran, M.E.; Brooker-McEldowney, M.; Heerema, N.A.; Jarjoura, D.; Schaaf, L.J.; Byrd, J.C.; Grever, M.R.; Dalton, J.T. Clinical response and pharmacokinetics from a phase 1 study of an active dosing schedule of flavopiridol in relapsed chronic lymphocytic leukemia. Blood, 2009, 113(12), 2637-2645.
[http://dx.doi.org/10.1182/blood-2008-07-168583] [PMID: 18981292]
[37]
Lin, T.S.; Ruppert, A.S.; Johnson, A.J.; Fischer, B.; Heerema, N.A.; Andritsos, L.A.; Blum, K.A.; Flynn, J.M.; Jones, J.A.; Hu, W.; Moran, M.E.; Mitchell, S.M.; Smith, L.L.; Wagner, A.J.; Raymond, C.A.; Schaaf, L.J.; Phelps, M.A.; Villalona-Calero, M.A.; Grever, M.R.; Byrd, J.C. Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease. J. Clin. Oncol., 2009, 27(35), 6012-6018.
[http://dx.doi.org/10.1200/JCO.2009.22.6944] [PMID: 19826119]
[38]
Bose, P.; Simmons, G.L.; Grant, S. Cyclin-dependent kinase inhibitor therapy for hematologic malignancies. Expert Opin. Investig. Drugs, 2013, 22(6), 723-738.
[http://dx.doi.org/10.1517/13543784.2013.789859] [PMID: 23647051]
[39]
Karp, J.E.; Blackford, A.; Smith, B.D.; Alino, K.; Seung, A.H.; Bolaños-Meade, J.; Greer, J.M.; Carraway, H.E.; Gore, S.D.; Jones, R.J.; Levis, M.J.; McDevitt, M.A.; Doyle, L.A.; Wright, J.J. Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia. Leuk. Res., 2010, 34(7), 877-882.
[http://dx.doi.org/10.1016/j.leukres.2009.11.007] [PMID: 19962759]
[40]
Baker, A.; Gregory, G.P.; Verbrugge, I.; Kats, L.; Hilton, J.J.; Vidacs, E.; Lee, E.M.; Lock, R.B.; Zuber, J.; Shortt, J.; Johnstone, R.W. The CDK9 inhibitor dinaciclib exerts potent apoptotic and antitumor effects in preclinical models of MLL-rearranged acute myeloid leukemia. Cancer Res., 2016, 76(5), 1158-1169.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1070] [PMID: 26627013]
[41]
Johnson, A.J.; Yeh, Y-Y.; Smith, L.L.; Wagner, A.J.; Hessler, J.; Gupta, S.; Flynn, J.; Jones, J.; Zhang, X.; Bannerji, R.; Grever, M.R.; Byrd, J.C. The novel cyclin-dependent kinase inhibitor dinaciclib (SCH727965) promotes apoptosis and abrogates microenvironmental cytokine protection in chronic lymphocytic leukemia cells. Leukemia, 2012, 26(12), 2554-2557.
[http://dx.doi.org/10.1038/leu.2012.144] [PMID: 22791353]
[42]
Hossain, D.M.S.; Javaid, S.; Cai, M.; Zhang, C.; Sawant, A.; Hinton, M.; Sathe, M.; Grein, J.; Blumenschein, W.; Pinheiro, E.M.; Chackerian, A. Dinaciclib induces immunogenic cell death and enhances anti-PD1–mediated tumor suppression. J. Clin. Invest., 2018, 128(2), 644-654.
[http://dx.doi.org/10.1172/JCI94586] [PMID: 29337311]
[43]
Shirsath, N.P.; Manohar, S.M.; Joshi, K.S. P276-00, a cyclin-dependent kinase inhibitor, modulates cell cycle and induces apoptosis in vitro and in vivo in mantle cell lymphoma cell lines. Mol. Cancer, 2012, 11(1), 77.
[http://dx.doi.org/10.1186/1476-4598-11-77] [PMID: 23075291]
[44]
Cassaday, R.D.; Goy, A.; Advani, S.; Chawla, P.; Nachankar, R.; Gandhi, M.; Gopal, A.K. A phase II, single-arm, open-label, multicenter study to evaluate the efficacy and safety of P276-00, a cyclin-dependent kinase inhibitor, in patients with relapsed or refractory mantle cell lymphoma. Clin. Lymphoma Myeloma Leuk., 2015, 15(7), 392-397.
[http://dx.doi.org/10.1016/j.clml.2015.02.021] [PMID: 25816934]
[45]
Mishra, P.B.; Lobo, A.S.; Joshi, K.S.; Rathos, M.J.; Kumar, G.A.; Padigaru, M. Molecular mechanisms of anti-tumor properties of P276-00 in head and neck squamous cell carcinoma. J. Transl. Med., 2013, 11(1), 42.
[http://dx.doi.org/10.1186/1479-5876-11-42] [PMID: 23414419]
[46]
Su, Y.T.; Chen, R.; Wang, H.; Song, H.; Zhang, Q.; Chen, L.Y.; Lappin, H.; Vasconcelos, G.; Lita, A.; Maric, D.; Li, A.; Celiku, O.; Zhang, W.; Meetze, K.; Estok, T.; Larion, M.; Abu-Asab, M.; Zhuang, Z.; Yang, C.; Gilbert, M.R.; Wu, J. Novel targeting of transcription and metabolism in glioblastoma. Clin. Cancer Res., 2018, 24(5), 1124-1137.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-2032] [PMID: 29254993]
[47]
Goh, K.C.; Novotny-Diermayr, V.; Hart, S.; Ong, L.C.; Loh, Y.K.; Cheong, A.; Tan, Y.C.; Hu, C.; Jayaraman, R.; William, A.D.; Sun, E.T.; Dymock, B.W.; Ong, K.H.; Ethirajulu, K.; Burrows, F.; Wood, J.M. TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties. Leukemia, 2012, 26(2), 236-243.
[http://dx.doi.org/10.1038/leu.2011.218] [PMID: 21860433]
[48]
Ponder, K.G.; Matulis, S.M.; Hitosugi, S.; Gupta, V.A.; Sharp, C.; Burrows, F.; Nooka, A.K.; Kaufman, J.L.; Lonial, S.; Boise, L.H. Dual inhibition of Mcl-1 by the combination of carfilzomib and TG02 in multiple myeloma. Cancer Biol. Ther., 2016, 17(7), 769-777.
[http://dx.doi.org/10.1080/15384047.2016.1192086] [PMID: 27246906]
[49]
Dolman, M.E.M.; Poon, E.; Ebus, M.E.; den Hartog, I.J.M.; van Noesel, C.J.M.; Jamin, Y.; Hallsworth, A.; Robinson, S.P.; Petrie, K.; Sparidans, R.W.; Kok, R.J.; Versteeg, R.; Caron, H.N.; Chesler, L.; Molenaar, J.J. Cyclin-dependent kinase inhibitor AT7519 as a potential drug for MYCN-dependent neuroblastoma. Clin. Cancer Res., 2015, 21(22), 5100-5109.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0313] [PMID: 26202950]
[50]
Dorward, D.A.; Felton, J.M.; Robb, C.T.; Craven, T.; Kipari, T.; Walsh, T.S.; Haslett, C.; Kefala, K.; Rossi, A.G.; Lucas, C.D. The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome. Thorax, 2017, 72(2), 182-185.
[http://dx.doi.org/10.1136/thoraxjnl-2016-209229] [PMID: 27965411]
[51]
Chen, E.X.; Hotte, S.; Hirte, H.; Siu, L.L.; Lyons, J.; Squires, M.; Lovell, S.; Turner, S.; McIntosh, L.; Seymour, L. A Phase I study of cyclin-dependent kinase inhibitor, AT7519, in patients with advanced cancer: NCIC Clinical Trials Group IND 177. Br. J. Cancer, 2014, 111(12), 2262-2267.
[http://dx.doi.org/10.1038/bjc.2014.565] [PMID: 25393368]
[52]
Syn, N.L.; Lim, P.L.; Kong, L.R.; Wang, L.; Wong, A.L.A.; Lim, C.M.; Loh, T.K.S.; Siemeister, G.; Goh, B.C.; Hsieh, W.S. Pan-CDK inhibition augments cisplatin lethality in nasopharyngeal carcinoma cell lines and Xenograft models. Signal Transduct. Target. Ther., 2018, 3(1), 9.
[http://dx.doi.org/10.1038/s41392-018-0010-0] [PMID: 29666673]
[53]
Lin, S.F.; Lin, J.D.; Hsueh, C.; Chou, T.C.; Wong, R.J. Activity of roniciclib in medullary thyroid cancer. Oncotarget, 2018, 9(46), 28030-28041.
[http://dx.doi.org/10.18632/oncotarget.25555] [PMID: 29963260]
[54]
Bahleda, R.; Grilley-Olson, J.E.; Govindan, R.; Barlesi, F.; Greillier, L.; Perol, M.; Ray-Coquard, I.; Strumberg, D.; Schultheis, B.; Dy, G.K.; Zalcman, G.; Weiss, G.J.; Walter, A.O.; Kornacker, M.; Rajagopalan, P.; Henderson, D.; Nogai, H.; Ocker, M.; Soria, J.C. Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies. Br. J. Cancer, 2017, 116(12), 1505-1512.
[http://dx.doi.org/10.1038/bjc.2017.92] [PMID: 28463960]
[55]
Cho, B.C.; Dy, G.K.; Govindan, R.; Kim, D.W.; Pennell, N.A.; Zalcman, G.; Besse, B.; Kim, J.H.; Koca, G.; Rajagopalan, P.; Langer, S.; Ocker, M.; Nogai, H.; Barlesi, F. Phase Ib/II study of the pan-cyclin-dependent kinase inhibitor roniciclib in combination with chemotherapy in patients with extensive-disease small-cell lung cancer. Lung Cancer, 2018, 123, 14-21.
[http://dx.doi.org/10.1016/j.lungcan.2018.04.022] [PMID: 30089585]
[56]
Cirstea, D.; Hideshima, T.; Santo, L.; Eda, H.; Mishima, Y.; Nemani, N.; Hu, Y.; Mimura, N.; Cottini, F.; Gorgun, G.; Ohguchi, H.; Suzuki, R.; Loferer, H.; Munshi, N.C.; Anderson, K.C.; Raje, N. Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia, 2013, 27(12), 2366-2375.
[http://dx.doi.org/10.1038/leu.2013.194] [PMID: 23807770]
[57]
van der Biessen, D.A.J.; Burger, H.; de Bruijn, P.; Lamers, C.H.J.; Naus, N.; Loferer, H.; Wiemer, E.A.C.; Mathijssen, R.H.J.; de Jonge, M.J.A. Phase I study of RGB-286638, a novel, multitargeted cyclin-dependent kinase inhibitor in patients with solid tumors. Clin. Cancer Res., 2014, 20(18), 4776-4783.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0325] [PMID: 25024258]
[58]
Locatelli, G.; Bosotti, R.; Ciomei, M.; Brasca, M.G.; Calogero, R.; Mercurio, C.; Fiorentini, F.; Bertolotti, M.; Scacheri, E.; Scaburri, A.; Galvani, A.; Pesenti, E.; De Baere, T.; Soria, J.C.; Lazar, V.; Isacchi, A. Transcriptional analysis of an E2F gene signature as a biomarker of activity of the cyclin-dependent kinase inhibitor PHA-793887 in tumor and skin biopsies from a phase I clinical study. Mol. Cancer Ther., 2010, 9(5), 1265-1273.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-1163] [PMID: 20423997]
[59]
Alzani, R.; Pedrini, O.; Albanese, C.; Ceruti, R.; Casolaro, A.; Patton, V.; Colotta, F.; Rambaldi, A.; Introna, M.; Pesenti, E.; Ciomei, M.; Golay, J. Therapeutic efficacy of the pan-cdk inhibitor PHA-793887 in vitro and in vivo in engraftment and high-burden leukemia models. Exp. Hematol., 2010, 38(4), 259-269.e2.
[http://dx.doi.org/10.1016/j.exphem.2010.02.004] [PMID: 20167248]
[60]
Massard, C.; Soria, J.C.; Anthoney, D.A.; Proctor, A.; Scaburri, A.; Pacciarini, M.A.; Laffranchi, B.; Pellizzoni, C.; Kroemer, G.; Armand, J.P.; Balheda, R.; Twelves, C.J. A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected hepatotoxicity in patients with solid tumors. Cell Cycle, 2011, 10(6), 963-970.
[http://dx.doi.org/10.4161/cc.10.6.15075] [PMID: 21368575]
[61]
Gelbert, L.M.; Cai, S.; Lin, X.; Sanchez-Martinez, C.; del Prado, M.; Lallena, M.J.; Torres, R.; Ajamie, R.T.; Wishart, G.N.; Flack, R.S.; Neubauer, B.L.; Young, J.; Chan, E.M.; Iversen, P.; Cronier, D.; Kreklau, E.; de Dios, A. Preclinical characterization of the CDK4/6 inhibitor LY2835219: In-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest. New Drugs, 2014, 32(5), 825-837.
[http://dx.doi.org/10.1007/s10637-014-0120-7] [PMID: 24919854]
[62]
Tripathy, D.; Bardia, A.; Sellers, W.R. Ribociclib (LEE011): Mechanism of action and clinical impact of this selective cyclin-dependent kinase 4/6 inhibitor in various solid tumors. Clin. Cancer Res., 2017, 23(13), 3251-3262.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-3157] [PMID: 28351928]
[63]
Klein, M.E.; Kovatcheva, M.; Davis, L.E.; Tap, W.D.; Koff, A. CDK4/6 inhibitors: The mechanism of action may not be as simple as once thought. Cancer Cell, 2018, 34(1), 9-20.
[http://dx.doi.org/10.1016/j.ccell.2018.03.023] [PMID: 29731395]
[64]
Heathcote, D.A.; Patel, H.; Kroll, S.H.B.; Hazel, P.; Periyasamy, M.; Alikian, M.; Kanneganti, S.K.; Jogalekar, A.S.; Scheiper, B.; Barbazanges, M.; Blum, A.; Brackow, J.; Siwicka, A.; Pace, R.D.M.; Fuchter, M.J.; Snyder, J.P.; Liotta, D.C.; Freemont, P.S.; Aboagye, E.O.; Coombes, R.C.; Barrett, A.G.M.; Ali, S. A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration. J. Med. Chem., 2010, 53(24), 8508-8522.
[http://dx.doi.org/10.1021/jm100732t] [PMID: 21080703]
[65]
Hazel, P.; Kroll, S.H.B.; Bondke, A.; Barbazanges, M.; Patel, H.; Fuchter, M.J.; Coombes, R.C.; Ali, S.; Barrett, A.G.M.; Freemont, P.S. Inhibitor selectivity for cyclin‐dependent kinase 7: A structural, thermodynamic, and modelling study. ChemMedChem, 2017, 12(5), 372-380.
[http://dx.doi.org/10.1002/cmdc.201600535] [PMID: 28125165]
[66]
Patel, H.; Periyasamy, M.; Sava, G.P.; Bondke, A.; Slafer, B.W.; Kroll, S.H.B.; Barbazanges, M.; Starkey, R.; Ottaviani, S.; Harrod, A.; Aboagye, E.O.; Buluwela, L.; Fuchter, M.J.; Barrett, A.G.M.; Coombes, R.C.; Ali, S. ICEC0942, an orally bioavailable selective inhibitor of CDK7 for cancer treatment. Mol. Cancer Ther., 2018, 17(6), 1156-1166.
[http://dx.doi.org/10.1158/1535-7163.MCT-16-0847] [PMID: 29545334]
[67]
Chipumuro, E.; Marco, E.; Christensen, C.L.; Kwiatkowski, N.; Zhang, T.; Hatheway, C.M.; Abraham, B.J.; Sharma, B.; Yeung, C.; Altabef, A.; Perez-Atayde, A.; Wong, K.K.; Yuan, G.C.; Gray, N.S.; Young, R.A.; George, R.E. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell, 2014, 159(5), 1126-1139.
[http://dx.doi.org/10.1016/j.cell.2014.10.024] [PMID: 25416950]
[68]
Christensen, C.L.; Kwiatkowski, N.; Abraham, B.J.; Carretero, J.; Al-Shahrour, F.; Zhang, T.; Chipumuro, E.; Herter-Sprie, G.S.; Akbay, E.A.; Altabef, A.; Zhang, J.; Shimamura, T.; Capelletti, M.; Reibel, J.B.; Cavanaugh, J.D.; Gao, P.; Liu, Y.; Michaelsen, S.R.; Poulsen, H.S.; Aref, A.R.; Barbie, D.A.; Bradner, J.E.; George, R.E.; Gray, N.S.; Young, R.A.; Wong, K-K. Erratum to Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor. Cancer Cell, 2015, 27(1), 149.
[http://dx.doi.org/10.1016/j.ccell.2014.12.007]
[69]
Kwiatkowski, N.; Zhang, T.; Rahl, P.B.; Abraham, B.J.; Reddy, J.; Ficarro, S.B.; Dastur, A.; Amzallag, A.; Ramaswamy, S.; Tesar, B.; Jenkins, C.E.; Hannett, N.M.; McMillin, D.; Sanda, T.; Sim, T.; Kim, N.D.; Look, T.; Mitsiades, C.S.; Weng, A.P.; Brown, J.R.; Benes, C.H.; Marto, J.A.; Young, R.A.; Gray, N.S. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature, 2014, 511(7511), 616-620.
[http://dx.doi.org/10.1038/nature13393] [PMID: 25043025]
[70]
Nagaraja, S.; Vitanza, N.A.; Woo, P.J.; Taylor, K.R.; Liu, F.; Zhang, L.; Li, M.; Meng, W.; Ponnuswami, A.; Sun, W.; Ma, J.; Hulleman, E.; Swigut, T.; Wysocka, J.; Tang, Y.; Monje, M. Transcriptional dependencies in diffuse intrinsic pontine glioma. Cancer Cell, 2017, 31(5), 635-652.e6.
[http://dx.doi.org/10.1016/j.ccell.2017.03.011] [PMID: 28434841]
[71]
Wang, Y.; Zhang, T.; Kwiatkowski, N.; Abraham, B.J.; Lee, T.I.; Xie, S.; Yuzugullu, H.; Von, T.; Li, H.; Lin, Z.; Stover, D.G.; Lim, E.; Wang, Z.C.; Iglehart, J.D.; Young, R.A.; Gray, N.S.; Zhao, J.J. CDK7-dependent transcriptional addiction in triple-negative breast cancer. Cell, 2015, 163(1), 174-186.
[http://dx.doi.org/10.1016/j.cell.2015.08.063] [PMID: 26406377]
[72]
Zhang, Y.; Zhou, L.; Bandyopadhyay, D.; Sharma, K.; Allen, A.J.; Kmieciak, M.; Grant, S. The covalent CDK7 inhibitor THZ1 potently induces apoptosis in multiple myeloma cells in vitro and in vivo. Clin. Cancer Res., 2019, 25(20), 6195-6205.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-3788] [PMID: 31358538]
[73]
Olson, C.M.; Liang, Y.; Leggett, A.; Park, W.D.; Li, L.; Mills, C.E.; Elsarrag, S.Z.; Ficarro, S.B.; Zhang, T.; Düster, R.; Geyer, M.; Sim, T.; Marto, J.A.; Sorger, P.K.; Westover, K.D.; Lin, C.Y.; Kwiatkowski, N.; Gray, N.S. Development of a selective CDK7 covalent inhibitor reveals predominant cell-cycle phenotype. Cell Chem. Biol., 2019, 26(6), 792-803.e10.
[http://dx.doi.org/10.1016/j.chembiol.2019.02.012] [PMID: 30905681]
[74]
Hu, S.; Marineau, J.J.; Rajagopal, N.; Hamman, K.B.; Choi, Y.J.; Schmidt, D.R.; Ke, N.; Johannessen, L.; Bradley, M.J.; Orlando, D.A.; Alnemy, S.R.; Ren, Y.; Ciblat, S.; Winter, D.K.; Kabro, A.; Sprott, K.T.; Hodgson, J.G.; Fritz, C.C.; Carulli, J.P.; di Tomaso, E.; Olson, E.R. Discovery and characterization of SY-1365, a selective, covalent inhibitor of CDK7. Cancer Res., 2019, 79(13), 3479-3491.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-0119] [PMID: 31064851]
[75]
Hu, S.; Marineau, J.; Hamman, K.; Bradley, M.; Savinainen, A.; Alnemy, S.; Rajagopal, N.; Orlando, D.; Chuaqui, C.; Olson, E. Abstract 4421: SY-5609, an orally available selective CDK7 inhibitor demonstrates broad anti-tumor activity in vivo. Cancer Res., 2019, 79(Suppl. 13), 4421-4421.
[http://dx.doi.org/10.1158/1538-7445.AM2019-4421]
[76]
Bacon, C.W.; D’Orso, I. CDK9: A signaling hub for transcriptional control. Transcription, 2019, 10(2), 57-75.
[http://dx.doi.org/10.1080/21541264.2018.1523668] [PMID: 30227759]
[77]
Franco, L.C.; Morales, F.; Boffo, S.; Giordano, A. CDK9: A key player in cancer and other diseases. J. Cell. Biochem., 2018, 119(2), 1273-1284.
[http://dx.doi.org/10.1002/jcb.26293] [PMID: 28722178]
[78]
Cidado, J.; Boiko, S.; Proia, T.; Ferguson, D.; Criscione, S.W.; San Martin, M.; Pop-Damkov, P.; Su, N.; Roamio Franklin, V.N.; Sekhar Reddy Chilamakuri, C.; D’Santos, C.S.; Shao, W.; Saeh, J.C.; Koch, R.; Weinstock, D.M.; Zinda, M.; Fawell, S.E.; Drew, L. AZD4573 is a highly selective CDK9 inhibitor that suppresses MCL-1 and induces apoptosis in hematologic cancer cells. Clin. Cancer Res., 2020, 26(4), 922-934.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-1853] [PMID: 31699827]
[79]
Wu, T.; Qin, Z.; Tian, Y.; Wang, J.; Xu, C.; Li, Z.; Bian, J. Recent developments in the biology and medicinal chemistry of CDK9 inhibitors: An update. J. Med. Chem., 2020, 63(22), 13228-13257.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00744] [PMID: 32866383]
[80]
Anda, S.; Rothe, C.; Boye, E.; Grallert, B. Consequences of abnormal CDK activity in S phase. Cell Cycle, 2016, 15(7), 963-973.
[http://dx.doi.org/10.1080/15384101.2016.1152423] [PMID: 26918805]
[81]
Galbraith, M.D.; Bender, H.; Espinosa, J.M. Therapeutic targeting of transcriptional cyclin-dependent kinases. Transcription, 2019, 10(2), 118-136.
[http://dx.doi.org/10.1080/21541264.2018.1539615] [PMID: 30409083]
[82]
Choi, H.J.; Jin, S.; Cho, H.; Won, H.Y.; An, H.W.; Jeong, G.Y.; Park, Y.U.; Kim, H.Y.; Park, M.K.; Son, T.; Min, K.W.; Jang, K.S.; Oh, Y.H.; Lee, J.Y.; Kong, G. CDK 12 drives breast tumor initiation and trastuzumab resistance viaWNT and IRS 1‐ErbB‐ PI 3K signaling. EMBO Rep., 2019, 20(10)e48058
[http://dx.doi.org/10.15252/embr.201948058] [PMID: 31468695]
[83]
Peng, F.; Yang, C.; Kong, Y.; Huang, X.; Chen, Y.; Zhou, Y.; Xie, X.; Liu, P. CDK12 promotes breast cancer progression and maintains stemness by activating c-myc/β-catenin signaling. Curr. Cancer Drug Targets, 2020, 20(2), 156-165.
[http://dx.doi.org/10.2174/1568009619666191118113220] [PMID: 31744448]
[84]
Hopkins, J.L.; Zou, L. Induction of BRCAness in triple-negative breast cancer by a CDK12/13 inhibitor improves chemotherapy. Cancer Cell, 2019, 36(5), 461-463.
[http://dx.doi.org/10.1016/j.ccell.2019.10.012] [PMID: 31715127]
[85]
Quereda, V.; Bayle, S.; Vena, F.; Frydman, S.M.; Monastyrskyi, A.; Roush, W.R.; Duckett, D.R. Therapeutic targeting of CDK12/CDK13 in triple-negative breast cancer. Cancer Cell, 2019, 36(5), 545-558.e7.
[http://dx.doi.org/10.1016/j.ccell.2019.09.004] [PMID: 31668947]
[86]
Zhang, T.; Kwiatkowski, N.; Olson, C.M.; Dixon-Clarke, S.E.; Abraham, B.J.; Greifenberg, A.K.; Ficarro, S.B.; Elkins, J.M.; Liang, Y.; Hannett, N.M.; Manz, T.; Hao, M.; Bartkowiak, B.; Greenleaf, A.L.; Marto, J.A.; Geyer, M.; Bullock, A.N.; Young, R.A.; Gray, N.S. Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors. Nat. Chem. Biol., 2016, 12(10), 876-884.
[http://dx.doi.org/10.1038/nchembio.2166] [PMID: 27571479]
[87]
Goel, S.; DeCristo, M.J.; Watt, A.C. BrinJones, H.; Sceneay, J.; Li, B.B.; Khan, N.; Ubellacker, J.M.; Xie, S.; Metzger-Filho, O.; Hoog, J.; Ellis, M.J.; Ma, C.X.; Ramm, S.; Krop, I.E.; Winer, E.P.; Roberts, T.M.; Kim, H.J.; McAllister, S.S.; Zhao, J.J. CDK4/6 inhibition triggers anti-tumour immunity. Nature, 2017, 548(7668), 471-475.
[http://dx.doi.org/10.1038/nature23465] [PMID: 28813415]
[88]
Schaer, D.A.; Beckmann, R.P.; Dempsey, J.A.; Huber, L.; Forest, A.; Amaladas, N.; Li, Y.; Wang, Y.C.; Rasmussen, E.R.; Chin, D.; Capen, A.; Carpenito, C.; Staschke, K.A.; Chung, L.A.; Litchfield, L.M.; Merzoug, F.F.; Gong, X.; Iversen, P.W.; Buchanan, S.; de Dios, A.; Novosiadly, R.D.; Kalos, M. The CDK4/6 inhibitor abemaciclib induces a T cell inflamed tumor microenvironment and enhances the efficacy of PD-L1 checkpoint blockade. Cell Rep., 2018, 22(11), 2978-2994.
[http://dx.doi.org/10.1016/j.celrep.2018.02.053] [PMID: 29539425]
[89]
Zhang, J.; Bu, X.; Wang, H.; Zhu, Y.; Geng, Y.; Nihira, N.T.; Tan, Y.; Ci, Y.; Wu, F.; Dai, X.; Guo, J.; Huang, Y.H.; Fan, C.; Ren, S.; Sun, Y.; Freeman, G.J.; Sicinski, P.; Wei, W. Cyclin D–CDK4 kinase destabilizes PD-L1 via cullin 3–SPOP to control cancer immune surveillance. Nature, 2018, 553(7686), 91-95.
[http://dx.doi.org/10.1038/nature25015] [PMID: 29160310]
[90]
Kruse, U.; Pallasch, C.P.; Bantscheff, M.; Eberhard, D.; Frenzel, L.; Ghidelli, S.; Maier, S.K.; Werner, T.; Wendtner, C.M.; Drewes, G. Chemoproteomics-based kinome profiling and target deconvolution of clinical multi-kinase inhibitors in primary chronic lymphocytic leukemia cells. Leukemia, 2011, 25(1), 89-100.
[http://dx.doi.org/10.1038/leu.2010.233] [PMID: 20944678]
[91]
Gao, N.; Dai, Y.; Rahmani, M.; Dent, P.; Grant, S. Contribution of disruption of the nuclear factor-kappaB pathway to induction of apoptosis in human leukemia cells by histone deacetylase inhibitors and flavopiridol. Mol. Pharmacol., 2004, 66(4), 956-963.
[http://dx.doi.org/10.1124/mol.104.002014] [PMID: 15235103]
[92]
Dai, Y.; Rahmani, M.; Grant, S. Proteasome inhibitors potentiate leukemic cell apoptosis induced by the cyclin-dependent kinase inhibitor flavopiridol through a SAPK/JNK- and NF-κB-dependent process. Oncogene, 2003, 22(46), 7108-7122.
[http://dx.doi.org/10.1038/sj.onc.1206863] [PMID: 14562039]
[93]
Lin, T.S.; Blum, K.A.; Fischer, D.B.; Mitchell, S.M.; Ruppert, A.S.; Porcu, P.; Kraut, E.H.; Baiocchi, R.A.; Moran, M.E.; Johnson, A.J.; Schaaf, L.J.; Grever, M.R.; Byrd, J.C. Flavopiridol, fludarabine, and rituximab in mantle cell lymphoma and indolent B-cell lymphoproliferative disorders. J. Clin. Oncol., 2010, 28(3), 418-423.
[http://dx.doi.org/10.1200/JCO.2009.24.1570] [PMID: 20008633]
[94]
Wu, Y.M.; Cieślik, M.; Lonigro, R.J.; Vats, P.; Reimers, M.A.; Cao, X.; Ning, Y.; Wang, L.; Kunju, L.P.; de Sarkar, N.; Heath, E.I.; Chou, J.; Feng, F.Y.; Nelson, P.S.; de Bono, J.S.; Zou, W.; Montgomery, B.; Alva, A.; Robinson, D.R.; Chinnaiyan, A.M. Inactivation of CDK12 delineates a distinct immunogenic class of advanced prostate cancer. Cell, 2018, 173(7), 1770-1782.e14.
[http://dx.doi.org/10.1016/j.cell.2018.04.034] [PMID: 29906450]
[95]
Li, Y.; Zhang, H.; Li, Q.; Zou, P.; Huang, X.; Wu, C.; Tan, L. CDK12/13 inhibition induces immunogenic cell death and enhances anti-PD-1 anticancer activity in breast cancer. Cancer Lett., 2020, 495, 12-21.
[http://dx.doi.org/10.1016/j.canlet.2020.09.011] [PMID: 32941949]
[96]
Siemeister, G.; Luecking, U.; Wagner, C.; Detjen, K.; Mc Coy, C.; Bosslet, K. Molecular and pharmacodynamic characteristics of the novel multi-target tumor growth inhibitor ZK 304709. Biomed. Pharmacother., 2006, 60(6), 269-272.
[http://dx.doi.org/10.1016/j.biopha.2006.06.003] [PMID: 16887322]
[97]
Cho, S.J.; Lee, S.S.; Kim, Y.J.; Park, B.D.; Choi, J.S.; Liu, L.; Ham, Y.M.; Moon Kim, B.; Lee, S.K. Xylocydine, a novel Cdk inhibitor, is an effective inducer of apoptosis in hepatocellular carcinoma cells in vitro and in vivo. Cancer Lett., 2010, 287(2), 196-206.
[http://dx.doi.org/10.1016/j.canlet.2009.06.011] [PMID: 19616371]
[98]
Ham, Y.M.; Choi, K.J.; Song, S.Y.; Jin, Y.H.; Chun, M.W.; Lee, S.K. Xylocydine, a novel inhibitor of cyclin-dependent kinases, prevents the tumor necrosis factor-related apoptosis-inducing ligand-induced apoptotic cell death of SK-HEP-1 cells. J. Pharmacol. Exp. Ther., 2004, 308(3), 814-819.
[http://dx.doi.org/10.1124/jpet.103.059568] [PMID: 14617691]
[99]
Wu, Y.; Chen, C.; Sun, X.; Shi, X.; Jin, B.; Ding, K.; Yeung, S.C.J.; Pan, J. Cyclin-dependent kinase 7/9 inhibitor SNS-032 abrogates FIP1-like-1 platelet-derived growth factor receptor α and bcr-abl oncogene addiction in malignant hematologic cells. Clin. Cancer Res., 2012, 18(7), 1966-1978.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-1971] [PMID: 22447844]
[100]
Kamath, A.V.; Chong, S.; Chang, M.; Marathe, P.H. P-glycoprotein plays a role in the oral absorption of BMS-387032, a potent cyclin-dependent kinase 2 inhibitor, in rats. Cancer Chemother. Pharmacol., 2005, 55(2), 110-116.
[http://dx.doi.org/10.1007/s00280-004-0873-3] [PMID: 15338193]
[101]
Caligiuri, M.; Becker, F.; Murthi, K.; Kaplan, F.; Dedier, S.; Kaufmann, C.; Machl, A.; Zybarth, G.; Richard, J.; Bockovich, N.; Kluge, A.; Kley, N. A proteome-wide CDK/CRK-specific kinase inhibitor promotes tumor cell death in the absence of cell cycle progression. Chem. Biol., 2005, 12(10), 1103-1115.
[http://dx.doi.org/10.1016/j.chembiol.2005.08.008] [PMID: 16242653]
[102]
Gray, N.S.; Wodicka, L.; Thunnissen, A.M.W.H.; Norman, T.C.; Kwon, S.; Espinoza, F.H.; Morgan, D.O.; Barnes, G.; LeClerc, S.; Meijer, L.; Kim, S.H.; Lockhart, D.J.; Schultz, P.G. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science, 1998, 281(5376), 533-538.
[http://dx.doi.org/10.1126/science.281.5376.533] [PMID: 9677190]
[103]
Villerbu, N.; Gaben, A.M.; Redeuilh, G.; Mester, J. Cellular effects of purvalanol A: A specific inhibitor of cyclin-dependent kinase activities. Int. J. Cancer, 2002, 97(6), 761-769.
[http://dx.doi.org/10.1002/ijc.10125] [PMID: 11857351]
[104]
Dhariwala, F.A.; Rajadhyaksha, M.S. An unusual member of the Cdk family: Cdk5. Cell. Mol. Neurobiol., 2008, 28(3), 351-369.
[http://dx.doi.org/10.1007/s10571-007-9242-1] [PMID: 18183483]

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