Recent research in selective cyclin-dependent kinase 4 inhibitors for anti-cancer treatment

Current Medicinal Chemistry

Volumn 16, Issue 36, 2009, Pages 4869-4888

  Liu, Ning ^a   Fang, Hao ^a   Li, Yanling ^b   Xu, Wenfang ^a  

^a SHANDONG UNIVERSITY   (China)

^b INNER MONGOLIA UNIVERSITY OF TECHNOLOGY   (China)

Author keywords

Anti cancer agents; CDK4; Cell cycle; Cyclin dependent kinases; G1 phase; Selective inhibitors; Tumor

Indexed keywords

1,7 ANNULATED INDOCARBAZOLE DERIVATIVE; 2 AMINOQUINAZOLINE DERIVATIVE; 2' HYDROXYCINNAMALDEHYDE; 4 PHENYLAMINOMETHYLENE ISOQUINOLINE 1, 3[2H,4H] DIONE DERIVATIVE; 5 ARYLAMINO 2 METHYL 1 4,7 DIOXOBENZOTHIAZOLE DERIVATIVE; 6 ACETYL 8 CYCLOPENTYL 5 METHYL 2 [5 (1 PIPERAZINYL) 2 PYRIDINYLAMINO] 8H PYRIDO[2,3 D]PYRIMIDIN 7 ONE; ANTINEOPLASTIC AGENT; ARYL[A]PYRROLO[3,4 C]CARBAZOLE DERIVATIVE; BENZOCARBAZOLE; CA 199; CA 224; CARBAZOLE DERIVATIVE; CINK 4; CYCLIN D1; CYCLIN DEPENDENT KINASE INHIBITOR; CYCLIN DEPENDENT KINASE INHIBITOR 4; DIOXOBENZOTHIAZOLE DERIVATIVE; FASCAPLYSIN; INDOLO [2,3 A]PYRROLO[3,4 C]CARBAZOLE DERIVATIVE; N ([9B] 5 OXO 2, 3, 5, 9B TETRAHYDRO 1H PYRROLO[2, 1 A] ISOINDOL 9 YL)N' PYRIDIN 2 YLUREA; N [9 OXO 9H FLUOREN 4 YL] N' PYRIDIN YLUREA; PYRIDO [2,3 D] PYRIMIDIN 7 DERIVATIVE; PYRIDO [2,3 D] PYRIMIDONE DERIVATIVE; PYRROLO[3,4]CARBAZOLE DERIVATIVE; SB 210878; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; CANCER INHIBITION; CELL CYCLE G1 PHASE; CELL CYCLE REGULATION; CLINICAL TRIAL; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG ISOLATION; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME STRUCTURE; HUMAN; NEOPLASM; NONHUMAN; REVIEW; STRUCTURE ACTIVITY RELATION; TUMOR CELL DESTRUCTION;

ANTINEOPLASTIC AGENTS; CARBAZOLES; CYCLIN-DEPENDENT KINASE 4; G1 PHASE; HUMANS; INDOLES; NEOPLASMS; PYRIMIDINES; QUINONES;

EID: 71949112795     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986709789909611     Document Type: Review

References (114)

1. Nurse, P. Gentic-control of cell-sizeat cell-division in yeast. Nature, 1975, 256, 547-551.
2. Morgan, D. O. Principles of CDK regulation. Nature, 1995, 374, 131-134.
3. Morgan, D. O. Cyclin-dependent kinases: engines, clocks, and microprocessors. Ann. Rev. Cell Dev. Biol., 1997, 13, 261-291
4. Dyson, N. The regulation of E2F by pRB-family proteins. Genes Dev., 1998, 12, 2245-2262.
5. Sherr, C. J.; Roberts, J. M. CDK inhibitors: positive and negative regulators of G(1)-phase progression. Genes Dev., 1999, 13, 1501-1512.
6. Malumbres, M.; Barbacid, M. To cycle or not to cycle: a critical decision in cancer. Nat. Rev. Cancer, 2001, 1, 222-231 (Pubitemid 33741897)
7. Malumbres, M.; Barbacid, M., Mammalian cyclin-dependent kinases. Trends Biochem. Sci., 2005, 30, 630-641
8. Knockaert, M.; Greengard, P.; Meijer, L., Pharmacological inhibitors of cyclin-dependent kinases. Trends Biochem. Sci., 2002, 23 (9), 417-425 (Pubitemid 35247771)
9. Chen, H. H.; Wang, Y. C.; Fann, M. J., Identification and characterization of the CDK12/cyclin L1 complex involved in alternative splicing regulation. Mol. Cell Biol., 2006, 26, 2736-2745
10. Berro, R.; Pedati, C.; Kehn-Hall, K.; Wu, W.; Klase, Z.; Even, Y.; Geneviere, A. M.; Ammosova, T.; Nekhai, S.; Kashanchi, F. CDK13, a new potential human immunodeficiency virus type 1 inhibitory factor regulating viral mRNA splicing. J. Virol., 2008, 82, 7155-7166
11. Owa, T.; Yoshino, H.; Yoshimatsu, K.; Nagasu, T. Cell cycle regulation in the G1 phase: a promising target for the development of new chemotherapeutic anticancer agents. Curr. Med. Chem., 2001, 8, 1487-1503 (Pubitemid 32894011)
12. Malumbres, M.; Barbacid, M. Cell cycle, CDKs and cancer: a changing paradigm. Nat. Rev. Cancer, 2009, 9, 153-166
13. Santamaria, D.; Barriere, C.; Cerqueira, A.; Hunt, S.; Tardy, C.; Newton, K.; Caceres, J. F.; Dubus, P.; Malumbres, M.; Barbacid, M. Cdk1 is sufficient to drive the mammalian cell cycle. Nature, 2007, 448, 811-815 (Pubitemid 47266342)
14. Wyatt, P. G.; Woodhead, A. J.; Berdini, V.; Boulstridge, J. A.; Carr, M. G.; Cross, D. M.; Davis, D. J.; Devine, L. A.; Early, T. R.; Feltell, R. E.; Lewis, E. J.; McMenamin, R. L.; Navarro, E. F.; O'Brien, M. A.; O'Reilly, M.; Reule, M.; Saxty, G.; Seavers, L. C.; Smith, D. M.; Squires, M. S.; Trewartha, G.; Walker, M. T.; Woolford, A. J. Identification of N-(4-piperidinyl)-4-(2,6- dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design. J. Med. Chem., 2008, 51, 4986-4999
15. Birault, V.; Harris, C. J.; Le, J.; Lipkin, M.; Nerella, R.; Stevens, A. Bringing kinases into focus: efficient drug design through the use of chemogenomic toolkits. Curr. Med. Chem., 2006, 13, 1735-1748
16. Sharma, P. S.; Sharma, R.; Tyagi, R., Inhibitors of cyclin dependent kinases: useful targets for cancer treatment. Curr. Cancer Drug Targets, 2008, 8, 53-75. (Pubitemid 351237910)
17. Pevarello, P.; Villa, M. Cyclin-dependent kinase inhibitors: a survey of the recent patent literature. Expert Opin. Ther. Pat., 2005, 15, 675-703. (Pubitemid 40894897)
18. Christian, B. A.; Grever, M. R.; Byrd, J. C.; Lin, T. S. Flavopiridol in the treatment of chronic lymphocytic leukemia. Curr. Opin. Oncol., 2007, 19, 573-578 (Pubitemid 47508863)
19. Fuse, E.; Kuwabara, T.; Sparreboom, A.; Sausville, E. A.; Figg, W. D. Review of UCN-01 development: A lesson in the importance of clinical pharmacology. J. Clin. Oncol., 2005, 45, 394-403.
20. 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.; Booker-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 I study of an active dosing schedule of flavopiridol in relapsed chronic lymphocytic leukemia. Blood, 2008, 113, 2637-2645.
21. Komina, O.; Wesierska-Gadek, J. Action of resveratrol alone or in combination with roscovitine, a CDK inhibitor, on cell cycle progression in human HL-60 leukemia cells. Biochem. Pharmacol., 2008, 76, 1554-1562.
22. Misra, R. N.; Xiao, H. Y.; Kim, K. S.; Lu, S.; Han, W. C.; Barbosa, S. A.; Hunt, J. T.; Rawlins, D. B.; Shan, W.; Ahmed, S. Z.; Qian, L.; Chen, B. C.; Zhao, R.; Bednarz, M. S.; Kellar, K. A.; Mulheron, J. G.; Batorsky, R.; Roongta, U.; Kamath, A.; Marathe, P.; Ranadive, S. A.; Sack, J. S.; Tokarski, J. S.; Pavletich, N. P.; Lee, F. Y.; Webster, K. R.; Kimball, S. D. N-(cycloalkylamino)acyl-2- aminothiazole inhibitors of cyclin-dependent kinase 2. N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4- piperidinecarboxamide (BMS-387032), a highly efficacious and selective antitumor agent. J. Med. Chem., 2004, 47, 1719-1728
23. Toogood, P. L.; Harvey, P. J.; Repine, J. T.; Sheehan, D. J.; VanderWel, S. N.; Zhou, H.; Keller, P. R.; McNamara, D. J.; Sherry, D.; Zhu, T.; Brodfuehrer, J.; Choi, C.; Barvian, M. R.; Fry, D. W. Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6. J. Med. Chem., 2005, 48, 2388-2406
24. Morris, M. C.; Gondeau, C.; Tainer, J. A.; Divita, G. Kinetic mechanism of activation of the Cdk2/cyclin A complex. Key role of the C-lobe of the Cdk. J. Biol. Chem., 2002, 277, 23847-23853
25. Bockstaele, L.; Coulonval, K.; Kooken, H.; Paternot, S.; Roger, P. P. Regulation of CDK4. Cell Div., 2006, 1, 25.
26. Takaki, T.; Echalier, A.; Brown, N. R.; Hunt, T.; Endicott, J. A.; Noble, M. E. The structure of CDK4/cyclin D3 has implications for models of CDK activation. Proc. Natl. Acad. Sci. U.S.A., 2009, 106, 4171-4176
27. Day, P. J.; Cleasby, A.; Tickle, I. J.; O'Reilly, M.; Coyle, J. E.; Holding, F. P.; McMenamin, R. L.; Yon, J.; Chopra, R.; Lengauer, C.; Jhoti, H. Crystal structure of human CDK4 in complex with a D-type cyclin. Proc. Natl. Acad. Sci. U S A., 2009, 106, 4166-4170
28. Diehl, J. A. Cycling to cancer with cyclin D1. Cancer Biol. Ther., 2002, 1, 226-231
29. Yu, Q.; Geng, Y.; Sicinski, P., Specific protection against breast cancers by cyclin D1 ablation. Nature, 2001, 411, 1017-1021 (Pubitemid 32612319)
30. Landis, M. W.; Pawlyk, B. S.; Li, T.; Sicinski, P.; Hinds, P. W. Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis. Cancer Cell, 2006, 9, 13-22.
31. Yu, Q.; Sicinska, E.; Geng, Y.; Ahnstrom, M.; Zagozdzon, A.; Kong, Y.; Gardner, H.; Kiyokawa, H.; Harris, L. N.; Stal, O.; Sicinski, P. Requirement for CDK4 kinase function in breast cancer. Cancer Cell, 2006, 9, 23-32. (Pubitemid 43069508)
32. Bartkova, J.; Lukas, J.; Guldberg, P.; Alsner, J.; Kirkin, A. F.; Zeuthen, J.; Bartek, J. The p16-cyclin D/Cdk4-pRb pathway as a functional unit frequently altered in melanoma pathogenesis. Cancer Res., 1996, 56, 5475-5483 (Pubitemid 27011383)
33. Bartkova, J.; Lukas, C.; Sorensen, C. S.; Meyts, E. R.; Skakkebaek, N. E.; Lukas, J.; Bartek, J. Deregulation of the RB pathway in human testicular germ cell tumours. J. Pathol., 2003, 200, 149-156 (Pubitemid 36748023)
34. Ortega, S.; Prieto, I.; Odajima, J.; Martin, A.; Dubus, P.; Sotillo, R.; Barbero, J. L.; Malumbres, M.; Barbacid, M. Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nat. Genet., 2003, 35, 25-31. (Pubitemid 37048592)
35. Tetsu, O.; McCormick, F. Proliferation of cancer cells despite CDK2 inhibition. Cancer Cell, 2003, 3, 233-245 (Pubitemid 37443879)
36. Braden, W. A.; McClendon, A. K.; Knudsen, E. S. Cyclin-dependent kinase 4/6 activity is a critical determinant of prereplication complex assembly. Oncogen, 2008, 27, 7083-7093
37. Faul, M. M.; Engler, T. A.; Sullivan, K. A.; Grutsch, J. L.; Clayton, M. T.; Martinelli, M. J.; Pawlak, J. M.; LeTourneau, M.; Coffey, D. S.; Pedersen, S. W.; Kolis, S. P.; Furness, K.; Malhotra, S.; Alawar, R. S.; Ray, J. E. Synthetic approaches to indolo[6,7- a]pyrrolo[3,4-c]carbazoles: potent cyclin D1/CDK4 inhibitors. J. Org. Chem., 2004, 69, 2967-2975
38. Noble, M. E.; Endicott, J. A.; Johnson, L. N. Protein kinase inhibitors: insights into drug design from structure. Science, 2004, 303, 1800-1805 (Pubitemid 38374863)
39. Hennequin, L. F.; Allen, J.; Breed, J.; Curwen, J.; Fennell, M.; Green, T. P.; Lambert-van der Brempt, C.; Morgentin, R.; Norman, R. A.; Olivier, A.; Otterbein, L.; Ple, P. A.; Warin, N.; Costello, G. N-(5-chloro-1,3-benzodioxol- 4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy) quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. J. Med. Chem., 2006, 49, 6465-6488
40. Schulze-Gahmen, U.; De Bondt, H. L.; Kim, S. H. High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: bound waters and natural ligand as guides for inhibitor design. J. Med. Chem., 1996, 39, 4540-4546
41. Cherry, M.; Williams, D. H. Recent kinase and kinase inhibitor Xray structures: mechanisms of inhibition and selectivity insights. Curr. Med. Chem., 2004, 11, 663-673
42. Massague, J., G1 cell-cycle control and cancer. Nature, 2004, 432, 298-306.
43. Sherr, C. J. Cancer cell cycles. Science, 1996, 274, 1672-1677
44. Weinberg, R. A. The retinoblastoma protein and cell cycle control. Cell, 1995, 81, 323-330
45. Harbour, J. W.; Dean, D. C. The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev., 2000, 14, 2393-2409
46. DeGregori, J.; Kowalik, T.; Nevins, J. R. Cellular targets for activation by the E2F1 transcription factor include DNA synthesis-and G1/S-regulatory genes. Mol. Cell Biol., 1995, 15, 4215-4224
47. Rosania, G. R.; Chang, Y. T. Targeting hyperproliferative disorders with cyclin dependent kinase inhibitors. Expert Opin. Therap. Patent , 2000, 10, 215-230.
48. Barvian, M.; Boschelli, D. H.; Cossrow, J.; Dobrusin, E.; Fattaey, A.; Fritsch, A.; Fry, D.; Harvey, P.; Keller, P.; Garrett, M.; La, F.; Leopold, W.; McNamara, D.; Quin, M.; Trumpp-Kallmeyer, S.; Toogood, P.; Wu, Z.; Zhang, E. Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J. Med. Chem., 2000, 43, 4606-4616
49. Shapiro, G. I., Cyclin-dependent kinase pathways as targets for cancer treatment. J. Clin. Oncol., 2006, 24, 1770-1783
50. Sellers, W. R.; Kaelin, W. G., Jr. Role of the retinoblastoma protein in the pathogenesis of human cancer. J. Clin. Oncol., 1997, 15, 3301-3312
51. Sharpless, N. E.; Bardeesy, N.; Lee, K. H.; Carrasco, D.; Castrillon, D. H.; Aguirre, A. J.; Wu, E. A.; Horner, J. W.; DePinho, R. A. Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis. Nature, 2001, 413, 86-91.
52. Ruas, M.; Peters, G. The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochim Biophys Acta 1998, 1378, F115-77. (Pubitemid 28530512)
53. Arnold, A.; Papanikolaou, A. Cyclin D1 in breast cancer pathogenesis. J. Clin. Oncol., 2005, 23, 4215-4224 (Pubitemid 46211327)
54. Williams, M. E.; Swerdlow, S. H.; Meeker, T. C. Chromosome t(11;14)(q13;q32) breakpoints in centrocytic lymphoma are highly localized at the bcl-1 major translocation cluster. Leukemia, 1993, 7, 1437-1440
55. Bergsagel, P. L.; Kuehl, W. M.; Zhan, F.; Sawyer, J.; Barlogie, B.; Shaughnessy, J., Jr. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood, 2005, 106, 296-303. (Pubitemid 40967205)
56. Bergsagel, P. L.; Kuehl, W. M., Molecular pathogenesis and a consequent classification of multiple myeloma. J. Clin. Oncol., 2005, 23, 6333-6338
57. Sotillo, R.; Renner, O.; Dubus, P.; Ruiz-Cabello, J.; Martin-Caballero, J.; Barbacid, M.; Carnero, A.; Malumbres, M. Cooperation between Cdk4 and p27kip1 in tumor development: a preclinical model to evaluate cell cycle inhibitors with therapeutic activity. Cancer Res., 2005, 65, 3846-3852 (Pubitemid 40616365)
58. Lu, H.; Schulze-Gahmen, U. Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition. J. Med. Chem., 2006, 49, 3826-3831 (Pubitemid 43967880)
59. Grillo, M.; Bott, M. J.; Khandke, N.; McGinnis, J. P.; Miranda, M.; Meyyappan, M.; Rosfjord, E. C.; Rabindran, S. K. Validation of cyclin D1/CDK4 as an anticancer drug target in MCF-7 breast cancer cells: Effect of regulated overexpression of cyclin D1 and siRNA-mediated inhibition of endogenous cyclin D1 and CDK4 expression. Breast Cancer Res. Treat., 2006, 95, 185-194
60. Markwalder, J. A.; Arnone, M. R.; Benfield, P. A.; Boisclair, M.; Burton, C. R.; Chang, C. H.; Cox, S. S.; Czerniak, P. M.; Dean, C. L.; Doleniak, D.; Grafstrom, R.; Harrison, B. A.; Kaltenbach, R. F., 3rd; Nugiel, D. A.; Rossi, K. A.; Sherk, S. R.; Sisk, L. M.; Stouten, P.; Trainor, G. L.; Worland, P.; Seitz, S. P. Synthesis and biological evaluation of 1-aryl-4,5-dihydro-1H-pyrazolo[3, 4-d]pyrimidin-4-one inhibitors of cyclin-dependent kinases. J. Med. Chem., 2004, 47, 5894-5911
61. Berthet, C.; Aleem, E.; Coppola, V.; Tessarollo, L.; Kaldis, P. Cdk2 knockout mice are viable. Curr. Biol., 2003, 13, 1775-1785 (Pubitemid 37274109)
62. Hu, M. G.; Deshpande, A.; Enos, M.; Mao, D.; Hinds, E. A.; Hu, G. F.; Chang, R.; Guo, Z.; Dose, M.; Mao, C.; Tsichlis, P. N.; Gounari, F.; Hinds, P. W. A requirement for cyclin-dependent kinase 6 in thymocyte development and tumorigenesis. Cancer Res., 2009, 69, 810-818
63. Carini, D. J.; Kaltenbach, R. F.; Liu, J.; Benfield, P. A.; Boylan, J.; Boisclair, M.; Brizuela, L.; Burton, C. R.; Cox, S.; Grafstrom, R.; Harrison, B. A.; Harrison, K.; Akamike, E.; Markwalder, J. A.; Nakano, Y.; Seitz, S. P.; Sharp, D. M.; Trainor, G. L.; Sielecki, T. M. Identification of selective inhibitors of cyclin dependent kinase 4. Bioorg. Med. Chem. Lett., 2001, 11, 2209-2211
64. Zhu, G.; Conner, S. E.; Zhou, X.; Shih, C.; Li, T.; Anderson, B. D.; Brooks, H. B.; Campbell, R. M.; Considine, E.; Dempsey, J. A.; Faul, M. M.; Ogg, C.; Patel, B.; Schultz, R. M.; Spencer, C. D.; Teicher, B.; Watkins, S. A. Synthesis, structure-activity relationship, and biological studies of indolocarbazoles as potent cyclin D1-CDK4 inhibitors. J. Med. Chem., 2003, 46, 2027-2030
65. Sanchez-Martinez, C.; Shih, C.; Faul, M. M.; Zhu, G.; Paal, M.; Somoza, C.; Li, T.; Kumrich, C. A.; Winneroski, L. L.; Xun, Z.; Brooks, H. B.; Patel, B. K.; Schultz, R. M.; DeHahn, T. B.; Spencer, C. D.; Watkins, S. A.; Considine, E.; Dempsey, J. A.; Ogg, C. A.; Campbell, R. M.; Anderson, B. A.; Wagner, J. Aryl[a]pyrrolo[3,4-c]carbazoles as selective cyclin D1-CDK4 inhibitors. Bioorg. Med. Chem. Lett., 2003, 13, 3835-3839
66. Sanchez-Martinez, C.; Shih, C.; Zhu, G.; Li, T.; Brooks, H. B.; Patel, B. K.; Schultz, R. M.; DeHahn, T. B.; Spencer, C. D.; Watkins, S. A.; Ogg, C. A.; Considine, E.; Dempsey, J. A.; Zhang, F. Studies on cyclin-dependent kinase inhibitors: indolo-[2,3-a]pyrrolo[3,4-c]carbazoles versus bis-indolylmaleimides. Bioorg. Med. Chem. Lett., 2003, 13, 3841-3846
67. Al-awar, R. S.; Ray, J. E.; Hecker, K. A.; Joseph, S.; Huang, J.; Shih, C.; Brooks, H. B.; Spencer, C. D.; Watkins, S. A.; Schultz, R. M.; Considine, E. L.; Faul, M. M.; Sullivan, K. A.; Kolis, S. P.; Carr, M. A.; Zhang, F. Preparation of novel aza-1,7-annulated indoles and their conversion to potent indolocarbazole kinase inhibitors. Bioorg. Med. Chem. Lett., 2004, 14, 3925-3928
68. Al-awar, R. S.; Ray, J. E.; Hecker, K. A.; Huang, J.; Waid, P. P.; Shih, C.; Brooks, H. B.; Spencer, C. D.; Watkins, S. A.; Patel, B. R.; Stamm, N. B.; Ogg, C. A.; Schultz, R. M.; Considine, E. L.; Faul, M. M.; Sullivan, K. A.; Kolis, S. P.; Grutsch, J. L.; Joseph, S. 1,7-annulated indolocarbazoles as cyclin-dependent kinase inhibitors. Bioorg. Med. Chem. Lett., 2004, 14, 3217-3220
69. Long, B. H.; Rose, W. C.; Vyas, D. M.; Matson, J. A.; Forenza, S. Discovery of antitumor indolocarbazoles: rebeccamycin, NSC 655649, and fluoroindolocarbazoles. Curr. Med. Chem.- Anticancer Agents, 2002, 2, 255-266 (Pubitemid 34649875)
70. Bergman, J.; Janosik, T.; Wahlstrom, N. Indolocarbazoles. Advances in Heterocyclic Chemistry, 2001, 80, 1-71.
71. Zhu, G.; Conner, S. E.; Zhou, X.; Chan, H. K.; Shih, C.; Engler, T. A.; Al-Awar, R. S.; Brooks, H. B.; Watkins, S. A.; Spencer, C. D.; Schultz, R. M.; Dempsey, J. A.; Considine, E. L.; Patel, B. R.; Ogg, C. A.; Vasudevan, V.; Lytle, M. L. Synthesis of 1,7-annulated indoles and their applications in the studies of cyclin dependent kinase inhibitors. Bioorg. Med. Chem. Lett., 2004, 14, 3057-3061
72. Kitagawa, M.; Higashi, H.; Jung, H. K.; Suzuki-Takahashi, I.; Ikeda, M.; Tamai, K.; Kato, J.; Segawa, K.; Yoshida, E.; Nishimura, S.; Taya, Y. The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J., 1996, 15, 7060-7069 (Pubitemid 27023276)
73. Brugarolas, J.; Moberg, K.; Boyd, S. D.; Taya, Y.; Jacks, T.; Lees, J. A. Inhibition of cyclin-dependent kinase 2 by p21 is necessary for retinoblastoma protein-mediated G1 arrest after gamma-irradiation. Proc. Natl. Acad. Sci. U.S.A., 1999, 96, 1002-1007
74. Engler, T. A.; Furness, K.; Malhotra, S.; Sanchez-Martinez, C.; Shih, C.; Xie, W.; Zhu, G.; Zhou, X.; Conner, S.; Faul, M. M.; Sullivan, K. A.; Kolis, S. P.; Brooks, H. B.; Patel, B.; Schultz, R. M.; DeHahn, T. B.; Kirmani, K.; Spencer, C. D.; Watkins, S. A.; Considine, E. L.; Dempsey, J. A.; Ogg, C. A.; Stamm, N. B.; Anderson, B. D.; Campbell, R. M.; Vasudevan, V.; Lytle, M. L. Novel, potent and selective cyclin D1/CDK4 inhibitors: indolo[6,7-a]pyrrolo[3,4- c]carbazoles. Bioorg. Med. Chem. Lett., 2003, 13, 2261-2267
75. Zhu, G.; Conner, S.; Zhou, X.; Shih, C.; Brooks, H. B.; Considine, E.; Dempsey, J. A.; Ogg, C.; Patel, B.; Schultz, R. M.; Spencer, C. D.; Teicher, B.; Watkins, S. A. Synthesis of quinolinyl/ isoquinolinyl[a]pyrrolo[3,4-c] carbazoles as cyclin D1/CDK4 inhibitors. Bioorg. Med. Chem. Lett., 2003, 13, 1231-1235
76. Wu, J. J.; Yarwood, D. R.; Sills, M. A.; Chaudhuri, B.; Muller, L.; Zurini, M. Measurement of cdk4 kinase activity using an affinity peptide-tagging technology. Comb. Chem. High Throughput Screen, 2000, 3, 27-36.
77. Soni, R.; O'Reilly, T.; Furet, P.; Muller, L.; Stephan, C.; Zumstein-Mecker, S.; Fretz, H.; Fabbro, D.; Chaudhuri, B. Selective in vivo and in vitro effects of a small molecule inhibitor of cyclin-dependent kinase 4. J. Natl. Cancer Inst., 2001, 93, 436-446
78. Huwe, A.; Mazitschek, R.; Giannis, A. Small molecules as inhibitors of cyclin-dependent kinases. Angew Chem. Int. Ed. Engl., 2003, 42, 2122-2138
79. Lai, J. Y.; Langston, S.; Adams, R.; Beevers, R. E.; Boyce, R.; Burckhardt, S.; Cobb, J.; Ferguson, Y.; Figueroa, E.; Grimster, N.; Henry, A. H.; Khan, N.; Jenkins, K.; Jones, M. W.; Judkins, R.; Major, J.; Masood, A.; Nally, J.; Payne, H.; Payne, L.; Raphy, G.; Raynham, T.; Reader, J.; Reader, V.; Reid, A.; Ruprah, P.; Shaw, M.; Sore, H.; Stirling, M.; Talbot, A.; Taylor, J.; Thompson, S.; Wada, H.; Walker, D. Preparation of kinase-biased compounds in the search for lead inhibitors of kinase targets. Med. Res. Rev., 2005, 25, 310-330
80. Beattie, J. F.; Breault, G. A.; Ellston, R. P.; Green, S.; Jewsbury, P. J.; Midgley, C. J.; Naven, R. T.; Minshull, C. A.; Pauptit, R. A.; Tucker, J. A.; Pease, J. E. Cyclin-dependent kinase 4 inhibitors as a treatment for cancer. Part 1: identification and optimisation of substituted 4,6-bis anilino pyrimidines. Bioorg. Med. Chem. Lett., 2003, 13, 2955-2960
81. Tu, S.; Zhang, J.; Zhu, X.; Xu, J.; Zhang, Y.; Wang, Q.; Jia, R.; Jiang, B. New potential inhibitors of cyclin-dependent kinase 4: design and synthesis of pyrido[2,3-d]pyrimidine derivatives under microwave irradiation. Bioorg. Med. Chem. Lett., 2006, 16, 3578-3581
82. Klutchko, S. R.; Hamby, J. M.; Boschelli, D. H.; Wu, Z.; Kraker, A. J.; Amar, A. M.; Hartl, B. G.; Shen, C.; Klohs, W. D.; Steinkampf, R. W.; Driscoll, D. L.; Nelson, J. M.; Elliott, W. L.; Roberts, B. J.; Stoner, C. L.; Vincent, P. W.; Dykes, D. J.; Panek, R. L.; Lu, G. H.; Major, T. C.; Dahring, T. K.; Hallak, H.; Bradford, L. A.; Showalter, H. D.; Doherty, A. M. 2-Substituted aminopyrido[2,3-d]pyrimidin-7(8H)-ones. structure-activity relationships against selected tyrosine kinases and in vitro and in vivo anticancer activity. J. Med. Chem.,1998, 41, 3276-3292
83. Boschelli, D. H.; Wu, Z.; Klutchko, S. R.; Showalter, H. D.; Hamby, J. M.; Lu, G. H.; Major, T. C.; Dahring, T. K.; Batley, B.; Panek, R. L.; Keiser, J.; Hartl, B. G.; Kraker, A. J.; Klohs, W. D.; Roberts, B. J.; Patmore, S.; Elliott, W. L.; Steinkampf, R.; Bradford, L. A.; Hallak, H.; Doherty, A. M. Synthesis and tyrosine kinase inhibitory activity of a series of 2-amino-8H-pyrido[2,3-d]pyrimidines: identification of potent, selective platelet-derived growth factor receptor tyrosine kinase inhibitors. J. Med. Chem., 1998, 41, 4365-4377
84. Trumpp-Kallmeyer, S.; Rubin, J. R.; Humblet, C.; Hamby, J. M.; Hollis Showalter, H. D. Development of a binding model to protein tyrosine kinases for substituted pyrido[2,3-d]pyrimidine inhibitors. J. Med. Chem.,1998, 41, 1752-1763
85. Sanmartin, C.; Dominguez, M. V.; Cordeu, L.; Cubedo, E.; Garcia-Foncillas, J.; Font, M.; Palop, J. A. Synthesis and biological evaluation of 2,4,6-functionalized derivatives of pyrido[2,3-d]pyrimidines as cytotoxic agents and apoptosis inducers. Arch. Pharm. (Weinheim), 2008, 341, 28-41.
86. Gray, N. S.; Wodicka, L.; Thunnissen, A. M.; 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, 533-538
87. Fry, D. W.; Bedford, D. C.; Harvey, P. H.; Fritsch, A.; Keller, P. R.; Wu, Z.; Dobrusin, E.; Leopold, W. R.; Fattaey, A.; Garrett, M. D. Cell cycle and biochemical effects of PD 0183812. A potent inhibitor of the cyclin D-dependent kinases CDK4 and CDK6. J. Biol. Chem., 2001, 276, 16617-16623 (Pubitemid 37411450)
88. Toogood, P. L. Cyclin-dependent kinase inhibitors for treating cancer. Med. Res. Rev., 2001, 21, 487-498
89. VanderWel, S. N.; Harvey, P. J.; McNamara, D. J.; Repine, J. T.; Keller, P. R.; Quin, J., 3rd; Booth, R. J.; Elliott, W. L.; Dobrusin, E. M.; Fry, D. W.; Toogood, P. L. Pyrido[2,3-d]pyrimidin-7-ones as specific inhibitors of cyclin-dependent kinase 4. J. Med. Chem., 2005, 48, 2371-2387
90. 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, 1427-1438
91. Lin, J.; Yan, X. J.; Chen, H. M. Fascaplysin, a selective CDK4 inhibitor, exhibit anti-angiogenic activity in vitro and in vivo. Cancer Chemother. Pharmacol., 2007, 59, 439-445
92. Soni, R.; Muller, L.; Furet, P.; Schoepfer, J.; Stephan, C.; Zumstein-Mecker, S.; Fretz, H.; Chaudhuri, B. Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product. Biochem. Biophys. Res. Commun., 2000, 275, 877-884
93. Pavletich, N. P. Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. J. Mol. Biol., 1999, 287, 821-828
94. Fabbro, D.; Buchdunger, E.; Wood, J.; Mestan, J.; Hofmann, F.; Ferrari, S.; Mett, H.; O'Reilly, T.; Meyer, T. Inhibitors of protein kinases: CGP 41251, a protein kinase inhibitor with potential as an anticancer agent. Pharmacol. Ther., 1999, 82, 293-301.
95. Hormann, A.; Chaudhuri, B.; Fretz, H. DNA binding properties of the marine sponge pigment fascaplysin. Bioorg. Med. Chem., 2001, 9, 917-921
96. Aubry, C.; Wilson, A. J.; Jenkins, P. R.; Mahale, S.; Chaudhuri, B.; Marechal, J. D.; Sutcliffe, M. J. Design, synthesis and biological activity of new CDK4-specific inhibitors, based on fascaplysin. Org. Biomol. Chem., 2006, 4, 787-801.
97. Mahale, S.; Aubry, C.; James Wilson, A.; Jenkins, P. R.; Marechal, J. D.; Sutcliffe, M. J.; Chaudhuri, B. CA224, a non-planar analogue of fascaplysin, inhibits Cdk4 but not Cdk2 and arrests cells at G0/G1 inhibiting pRB phosphorylation. Bioorg. Med. Chem. Lett., 2006, 16, 4272-4278
98. Garcia, M. D.; Wilson, A. J.; Emmerson, D. P.; Jenkins, P. R.; Mahale, S.; Chaudhuri, B. Synthesis, crystal structure and biological activity of beta-carboline based selective CDK4-cyclin D1 inhibitors. Org. Biomol. Chem., 2006, 4, 4478-4484
99. Aubry, C.; Patel, A.; Mahale, S.; Chaudhuri, B.; Marechal, J. D.; Suteliffe, M. J.; Jenkins, P. R. The design and synthesis of novel 3-[2-indol-1-yl-ethyl]-1-H-indole derivatives as selective inhibitors of CDK4. Tetrahedron Lett., 2005, 46, 1423-1425. (Pubitemid 40215036)
100. Mahale, S.; Aubry, C.; Jenkins, P. R.; Marechal, J. D.; Sutcliffe, M. J.; Chaudhuri, B. Inhibition of cancer cell growth by cyclin dependent kinase 4 inhibitors synthesized based on the structure of fascaplysin. Bioorg. Chem., 2006, 34, 287-297 (Pubitemid 44374637)
101. Ryu, C. K.; Lee, I. K.; Jung, S. H.; Lee, C. O. Synthesis and cytotoxic activities of 6-chloro-7-arylamino-5,8-isoquinolinediones. Bioorg. Med. Chem. Lett., 1999, 9, 1075-1080
102. Ryu, C. K.; Kang, H. Y.; Lee, S. K.; Nam, K. A.; Hong, C. Y.; Ko, W. G.; Lee, B. H. 5-Arylamino-2-methyl-4,7-dioxobenzothiazoles as inhibitors of cyclin-dependent kinase 4 and cytotoxic agents. Bioorg. Med. Chem. Lett., 2000, 10, 461-464
103. Kwon, B. M.; Cho, Y. K.; Lee, S. H.; Nam, J. Y.; Bok, S. H.; Chun, S. K.; Kim, J. A.; Lee, I. R. 2′-Hydroxycinnamaldehyde from stem bark of Cinnamomum cassia. Planta. Med., 1996, 62, 183-184 (Pubitemid 126425821)
104. Kwon, B. M.; Lee, S. H.; Cho, Y. K.; Bok, S. H.; So, S. H.; Youn, M. R.; Chang, S. I. Synthesis and biological activity of cinnamaldehydes as angiogenesis inhibitors. Bioorg. Med. Chem. Lett., 1997, 7 , 2473-2476.
105. Lee, C. W.; Hong, D. H.; Han, S. B.; Park, S. H.; Kim, H. K.; Kwon, B. M.; Kim, H. M. Inhibition of human tumor growth by 2′-hydroxy- and 2′-benzoyloxycinnamaldehydes. Planta Med., 1999, 65, 263-266 (Pubitemid 29186085)
106. Kwon, B. M.; Lee, S. H.; Choi, S. U.; Park, S. H.; Lee, C. O.; Cho, Y. K.; Sung, N. D.; Bok, S. H. Synthesis and in vitro cytotoxicity of cinnamaldehydes to human solid tumor cells. Arch. Pharm. Res., 1998, 2 , 147-152
107. Jeong, H. W.; Kim, M. R.; Son, K. H.; Han, M. Y.; Ha, J. H.; Garnier, M.; Meijer, L.; Kwon, B. M. Cinnamaldehydes inhibit cyclin dependent kinase 4/cyclin D1. Bioorg. Med. Chem. Lett., 2000, 10, 1819-1822
108. Honma, T.; Hayashi, K.; Aoyama, T.; Hashimoto, N.; Machida, T.; Fukasawa, K.; Iwama, T.; Ikeura, C.; Ikuta, M.; Suzuki-Takahashi, I.; Iwasawa, Y.; Hayama, T.; Nishimura, S.; Morishima, H. Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design. J. Med. Chem., 2001, 44, 4615-4627 (Pubitemid 33144471)
109. Honma, T.; Yoshizumi, T.; Hashimoto, N.; Hayashi, K.; Kawanishi, N.; Fukasawa, K.; Takaki, T.; Ikeura, C.; Ikuta, M.; Suzuki-Takahashi, I.; Hayama, T.; Nishimura, S.; Morishima, H. A novel approach for the development of selective Cdk4 inhibitors: library design based on locations of Cdk4 specific amino acid residues. J. Med. Chem., 2001, 44, 4628-4640
110. Bathini, Y.; Singh, I.; Harvey, P. J.; Keller, P. R.; Singh, R.; Micetich, R. G.; Fry, D. W.; Dobrusin, E. M.; Toogood, P. L. 2-Aminoquinazoline inhibitors of cyclin-dependent kinases. Bioorg. Med. Chem. Lett., 2005, 15, 3881-3885
111. Tsou, H. R.; Otteng, M.; Tran, T.; Floyd, M. B., Jr.; Reich, M.; Birnberg, G.; Kutterer, K.; Ayral-Kaloustian, S.; Ravi, M.; Nilakantan, R.; Grillo, M.; McGinnis, J. P.; Rabindran, S. K. 4-(Phenylaminomethylene) isoquinoline-1,3(2H,4H)-diones as potent and selective inhibitors of the cyclin-dependent kinase 4 (CDK4). J. Med. Chem., 2008, 51, 3507-3525
112. Dickson, M. A.; Schwartz, G. K. Development of cell-cycle inhibitors for cancer therapy. Curr. Oncol., 2009, 16, 36-43.
113. Heady, L.; Fernandez-Serra, M.; Mancera, R. L.; Joyce, S.; Venkitaraman, A. R.; Artacho, E.; Skylaris, C. K.; Ciacchi, L. C.; Payne, M. C. Novel structural features of CDK inhibition revealed by an ab initio computational method combined with dynamic simulations. J. Med. Chem., 2006, 49, 5141-5153
114. Malumbres, M.; Pevarello, P.; Barbacid, M.; Bischoff, J. R. CDK inhibitors in cancer therapy: what is next? Trends Pharmacol. Sci., 2008, 29, 16-21.