Small-molecule inhibitors of Bcl-2 protein

Drugs of the Future

Volumn 29, Issue 4, 2004, Pages 369-381

  Pulley, Heather ^a   Mohammad, Ramzi ^a  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; 2 AMINO 6 BROMO 4 (1 CYANO 2 ETHOXY 2 OXOETHYL) 4H CHROMENE 3 CARBOXYLIC ACID ETHYL ESTER; ANTIMYCIN A1; ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; APOPTOSIS INHIBITOR; BH3 PROTEIN; BL 193; BORTEZOMIB; CASPASE 3; CASPASE 9; CELL PROTEIN; CPM 1285; CYTOTOXIC AGENT; ERLOTINIB; GEFITINIB; IXABEPILONE; OBLIMERSEN; ORGANIC COMPOUND; PEPTIDE DERIVATIVE; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN BID; PROTEIN BIK; PROTEIN INHIBITOR; PROTEIN P53; REGULATOR PROTEIN; TETROCARCIN A; TW 37; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AMINO ACID SEQUENCE; ANEMIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BINDING AFFINITY; BLOOD TOXICITY; CANCER; CANCER CELL; CANCER CELL CULTURE; CELL DEATH; CELL SURVIVAL; CONFORMATIONAL TRANSITION; DIMERIZATION; DRUG CONFORMATION; DRUG DESIGN; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; HUMAN; HYPERGLYCEMIA; MOLECULAR SIZE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; REGULATORY MECHANISM; REVIEW; SKIN INFECTION; TARGET CELL; TECHNIQUE; THROMBOCYTOPENIA; TRANSLATION REGULATION;

EID: 2642546354     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2004.029.04.795190     Document Type: Review

References (75)

1. Cosulich, S., Worrall, V., Hedge, P., Green, S., Clarke, P. Regulation of apoptosis by BH3 domains in a cell-free system. Curr Biol 1997, 7: 913-20.
2. Rutledge, S., Chin, J., Schepartz, A. A view to kill: Ligands for Bcl-2 family proteins. Curr Opin Chem Biol 2002, 6: 479-85.
3. Borner, C. The Bcl-2 protein family: Sensors and checkpoints for life-or-death decisions. Mol Immunol 2003, 39: 615-47.
4. Zhang, H., Taylor, J., Luther, D. et al. Antisense oligonucleotide inhibition of Bcl-XL and Bid expression in liver regulates responses in a mouse model of fas-induced fulminant hepatitis. J Pharmacol Exp Ther 2003, 307: 24-33.
5. Sattler, M., Liang, H., Nattesheim, D. et al. Structure of Bcl-XL-Bak peptide complex: Recognition between regulators of apoptosis. Science 1997, 275: 983-6.
6. Johnstone, R., Ruefli, A., Lowe, S. Apoptosis: A link between cancer genetics and chemotherapy. Cell 2002, 108: 153-64.
7. Shimizu, S., Konishi, A., Kodama, T., Tsujimoto, Y. BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death. Proc Natl Acad Sci USA 2000, 97: 3100-5.
8. Baell, J., Huang, D. Prospects for target in the Bcl-2 family of proteins to develop novel cytotoxic drugs. Biochem Pharmacol 2002, 64: 851-63.
9. Zha, H., Aime-Sempe, C., Sato, T., Reed, J. Proapoptotic protein Bas heterodimerizes with Bcl-2 and homodimerizes with Bax via a novel domain distinct from BH1 and BH2. J Biol Chem 1996, 271: 7440-4.
10. Degeterev, A., Lugovskoy, A., Chardone, M., Mulley, B., Wagner, G., Mitchison, T., Yuan, J. Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-XL. Nat Cell Biol 2001, 3: 173-82.
11. Solary, E., Bettaieb, A., Dubrez-Daloz, L., Corcos, L. Mitochondria as a target for inducing death of malignant hematopoietic cells. Leuk Lymphoma 2003, 44: 563-74.
12. Huang, Z. The chemical biology of apoptosis; exploring protein-protein interactions and the life and death of cells with small molecules. Chem Biol 2002, 9: 1059-72.
13. Huang, Z., Liu, D. Synthetic peptides and non-peptidic molecules as probes of structure and function of Bcl-2 family proteins and modulators of apoptosis. Apoptosis 2001, 6: 453-62.
14. Hinz, S., Trauzold, A., Boenicke, L. et al. Bcl-XL protects pancreatic adenocarcinoma cells against CD95- and TRAIL-receptor-mediated apoptosis. Oncogene 2000, 19: 5477-86.
15. Lugovskoy, A., Degterev, A., Fahmy, A., Zhou, P., Gross, J., Yuan, J., Wagner, G. A novel approach for characterizing protein ligand complexes: Molecular basis for specificity of small-molecule Bcl-2 inhibitors. J Am Chem Soc 2002, 124: 1234-40.
16. Reed, J. Mechanisms of apoptosis avoidance in cancer. Curr Opin Oncol 1999, 11: 68-75.
17. Tzung, S., Kim, K., Basanez, G. et al. Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3. Nat Cell Biol 2001, 3: 183-90.
18. McPake, C., Tillman, D., Poquette, C., George, E., Houghton, J., Harris, I. Bax is an important determinant of chemosensitivity in pediatric tumor cell lines independent of Bcl-2 expression and p53 status. Oncol Res 1998, 10: 235-44.
19. Amundson, S., Myers, T., Scudiero, D., Kitada, S., Reed, J., Fornace, A. An informative approach identifying markers of chemosensitivity in human cancer cell lines. Cancer Res 2000, 60: 6101-10.
20. Liu, R., Page, C., Beidler, D., Wicha, M., Nunez, G. Overexpression of Bcl-XL promotes chemotherapy resistance of mammary tumors in a syngenic murine model. Am J Pathol 1999, 155: 1861-7.
21. Ghaneh, P., Kawesha, A., Evans, J., Neoptolemos, J. Molecular prognostic markers in pancreatic cancer. J Hepatobiliary Pancreat Surg 2002, 9: 1-11.
22. Peczuh, M., Hamilton, A. Peptide and protein recognition by designed molecules. Chem Rev 2000, 100: 2479-94.
23. Fahmy, A., Wagner, G. TreeDock: A tool for protein docking based on minimizing van der Waals energies. J Am Chem Soc 2002, 124: 1241-50.
24. Jansen, B., Wachek, V., Heere-Ress, E. Chemosensitisation of malignant melanoma by Bcl2 antisense therapy. Lancet 2000, 356: 1728-33.
25. Webb, A., Cunningham, D., Cotter, F. et al. BCL-2 antisene therapy in patients with non-Hodgkin lymphoma. Lancet 1997, 349: 1137-41.
26. Frankel, S. Oblimersen sodium (G3139 Bcl-2 antisense oligonucleotide) therapy in Waldenstrom's macroglobulinemia: A targeted approach to enhance apoptosis. Semin Oncol 2003, 30: 300-4.
27. Wang, J., Zhang, Z., Choksi, S. et al. Cell permeable Bcl-2 binding peptides; a chemical approach to apoptosis induction in tumor cells. Cancer Res 2000, 60: 1498-1502.
28. Enyedy, I., Ling, Y., Nacro, K. et al. Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening. J Med Chem 2001, 44: 4313-24.
29. Wang, J., Liu, D., Zhang, Z. et al. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc Natl Acad Sci USA 2000, 97: 7124-9.
30. Yamaguchi, H., Paranawithana, S., Lee, M., Huang, Z., Bhalla, K., Wang, H. Epothilone B analogue (BMS-247550)-mediated cytotoxicity through induction of Bax conformational change in human breast cancer cells. Cancer Res 2002, 62: 466-71.
31. Pei, X., Dai, Y., Grant, S. The proteasome inhibitor bortezomib promotes mitochondrial injury and apoptosis induced by the small molecule Bcl-2 inhibitor HA14-1 in multiple myeloma cells. Leukemia 2003, 17: 2036-45.
32. Lickliter, J., Wood, N., Johnson, L., McHugh, G., Tan, J., Wood, F., Cox, J., Wickham, N. HA14-1 selectively induces apoptosis in Bcl-2-overexpressing leukemia/lymphoma cells, and enhances cytarabine-induced cell death. Leukemia 2003, 17: 2074-80.
33. Nakashima, T., Miura, M., Hara, M. Tetrocarcin A inhibits mitochondrial functions of Bcl-2 and suppresses its anti-apoptotic activity. Cancer Res 2000, 60: 1229-35.
34. Kaneko, M., Nakashima, T., Uosaki, Y., Hara, M., Ikeda, S., Kanda, Y. Synthesis of tetrocarcin derivatives with specific inhibitory activity towards Bcl-2 functions. Bioorg Med Chem Lett 2001, 11: 887-90.
35. Tinhofer, I., Anether, G., Senfter, M., Pfaller, K., Bernhard, D., Hara, M., Greil, R. Stressful death of T-ALL tumor cells after treatment with the anti-tumor agent tetrocarcin-A. FASEB J 2002, 16: 1295-8.
36. Anether, G., Tinhofer, I., Senfter, M., Greil, R. Tetrocarcin-A-induced ER stress mediates apoptosis in B-CLL cells via a Bcl-2-independent pathway. Blood 2003, 101: 4561-8.
37. Manion, M., O'Neil, J., Giedt, C., Kim, K., Zhang, K., Hockenbury, D. Bcl-XL mutations suppress cellular sensitivity to antimycin A. J Biol Chem 2003, 279: 2159-65.
38. Kim, K., Giedt, C., Basanez, G. et al. Biophysical characterization of recombinant human Bcl-2 and its interactions with an inhibitory ligand, antimycin A. Biochemistry 2001, 40: 4911-22.
39. 2+. Neurochem Res 2003, 28: 1201-11.
40. Kutzki, O., Park, H., Ernst, J., Orner, B., Yin, H., Hamilton, A. Development of a potent Bcl-XL antagonist based on α-helix mimicry. J Am Chem Soc 2002, 124: 11838-9.
41. Ernst, J., Becerril, J., Park, H., Yin, H., Hamilton, A. Design and application of an α-helix-mimetic scaffold based on an oligoamide-foldamer strategy: Antagonism of the Bak BH3/Bcl-xl complex. Angew Chem Int Ed 2003, 42: 535-9.
42. Chmura, S., Dolan, M., Cha, A., Mauceri, H., Kufe, D., Weichselbaum, R. In vitro and in vivo activity of protein kinase C inhibitor chelerythrine chloride induces tumor cell toxicity and growth delay in vivo. Clin Cancer Res 2000, 6: 737-42.
43. Chan, S., Lee, M., Tan, K. et al. Identification of chelerythrine as an inhibitor of Bcl-XL function. J Biol Chem 2003, 278(23): 20453-6.
44. Tan, Y., Teng, E., Ting, A. A small inhibitor of the interaction between Bax and Bcl-XL can synergize with methylprednisolone to induce apoptosis in Bcl-XL-overexpressing breast cancer cells. J Cancer Res Clin Oncol 2003, 129: 437-48.
45. Bianco, C., Tortora, G., Bianco, R. et al. Enhancement of antitumor activity of ionizing radiation by combined treatment with the selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 (Iressa). Clin Cancer Res 2002, 8: 3250-8.
46. Milella, M., Estrov, Z., Kornblau, S. et al. Synergistic induction of apoptosis by simultaneous disruption of the Bcl-2 and MEK/MAPK pathways in acute myelogenous leukemia. Blood 2002, 99: 3461-4.
47. Koo, H., VanBrocklin, M., McWilliams, M., Leppla, S., Duesbery, N., Woude, G. Apoptosis and melanogenesis in human melanoma cells induced by anthrax lethal factor inactivation of mitogen-activatd protein kinase kinase. Proc Natl Acad Sci USA 2002, 99: 3052-7.
48. Cochran, A. Protein-protein interfaces: Mimics and inhibitors. Curr Opin Chem Biol 2001, 5: 654-9.
49. Majeux, N., Scarsi, M., Caflisch, A. Efficient electrostatic solvation model for protein-fragment docking. Protein 2001, 42: 256-68.
50. Jenkins, J., Kao, R., Shapiro, R. Virtual screening to enrich hit lists from high-throughput screening: A case study on small-molecule inhibitors of angiogenin. Proteins 2003, 50: 81-93.
51. Greenbaum, D., Arnold, W., Lu, F. Small molecule affinity fingerprinting: A tool for enzyme family subclassification, target identification, and inhibitor design. Chem Biol 2002, 9: 1085-94.
52. Jahnke, W. Spin labels as a tool to identify and characterize protein-ligand interactions by NMR spectroscopy. ChemBioChem 2002, 3: 167-73.
53. Moore, J. NMR techniques for characterization of ligand binding: Utility for lead generation and optimization in drug discovery. Biopolymers 1999, 51(3): 221-43.
54. Andreeff, M., Jiang, S., Zhang, X. Expression of Bcl-2-related genes in normal and Aml progenitors: Changes induced by chemotherapy and retinoic acid. Leukemia 1999, 13: 1881-92.
55. Yeh, F., Wu, C., Lee, H. Signaling pathway for aloe-emodin-induced apoptosis in human H460 lung nonsmall carcinoma cell. Intl J Cancer 2003, 106: 26-33.
56. Dai, Y., Grant, S. Cyclin-dependent kinase inhibitors. Curr Opin Pharmacol 2003, 3: 362-70.
57. Grant, S., Roberts, J. The use of cyclin-dependent kinase inhibitors alone or in combination with established cytotoxic drugs in cancer chemotherapy. Drug Resist Updates 2003, 6: 15-26.
58. Senderowicz, A. Novel direct and indirect cyclin-dependent kinase modulators for the prevention and treatment of human neoplasms. Cancer Chemother Pharmacol 2003, 52(Suppl. 1): S61-S73.
59. Krajewska, M., Krajewski, S., Banares, S. Elevated expression of inhibitor of apoptosis proteins in prostate cancer. Clin Cancer Res 2003, 9: 4914-25.
60. Beauparlant, P., Shore, G. Therapeutic activation of caspases in cancer: A question of selectivity. Curr Opin Drug Discov Devel 2003, 6: 179-87.
61. Schimmer, A., Munk-Pedersen, I., Minden, M., Reed, J. Bcl-2 and apoptosis in chronic lymphocytic leukemia. Curr Treat Options Oncol 2003, 4: 211-8.
62. Ling, Y., Liebes, L., Zou, Y., Perez-Soler, R. Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic response to bortezomib, a novel proteasome inhibitor, in human H460 non-small cell lung cancer cells. J Biol Chem 2003, 278: 33714-23.
63. Motoyama, A., Hynes, N. BAD: A good therapeutic target? Breast Cancer Res 2003, 5: 27-30.
64. Bonomi, P. Clinical studies with non-Iressa EGFR tyrosine kinase inhibitors. Lung Cancer 2003, 41(Suppl. 1): S43-8.
65. Grunwald, V., Hidalgo, M. Developing inhibitors of the epidermal growth factor receptor for cancer treatment. J Natl Cancer Inst 2003, 95: 851-63.
66. Baselga, J. Why the epidermal growth factor receptor? The rationale for cancer therapy. Oncologist 2002, 7(Suppl. 4): 2-8.
67. Filleur, S., Courtin, A., Ait-Si-Ali, S. SiRNA-mediated inhibition of vascular endothelial growth factor severely limits tumor resistance to antiangiogenic thrombospondin-1 and slows tumor vascularization and growth. Cancer Res 2003, 63: 3919-22.
68. West, K., Castillo, S., Dennis, P. Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug Resist Updates 2002, 5: 234-48.
69. Evan, G., Littlewood, T. A matter of life and cell death. Science 1998, 281: 1317-22.
70. Jansen, B., Schlagbauer-Wadl, H., Kahr, H. Novel ras antagonist blocks human melanoma growth. Proc Natl Acad Sci USA 1999, 96: 14019-24.
71. Takai, Y., Sasaki, T., Matozaki, T. Small GTP-binding proteins. Physiol Rev 2001, 81: 153-85.
72. Jenal, A., Murray, T., Samuels, A., Ghafoor, A., Ward, E., Thun, M. Cancer statistics, 2003. Cancer J Clinicians 2003, 53: 5-26.
73. Steffens, T., Bajorin, D., Chapman, P. A phase II trial of high-dose cisplatin and dacarbazine. Lack of efficacy of high-dose, cisplatin-based therapy for metastatic melanoma. Cancer 1991, 68: 1230-7.
74. Bettaieb, A., Dubrez-Daloz, L., Launay, S., Plenchette, S., Ree, C., Cathelin, S., Solary, E. Bcl-2 proteins; targets and tools for chemosensitisation of tumor cells. Curr Med Chem Anti-Cancer Agents 2003, 3: 307-18.
75. Zheng, T. Death by design: The big debut of small molecules. Nat Cell Biol 2001, 3: E1-3.