Bcl-2 inhibitors: Emerging drugs in cancer therapy

Current Medicinal Chemistry

Volumn 19, Issue 12, 2012, Pages 1804-1820

  Bodur, C ^a   Basaga, H ^a  

^a SABANCI UNIVERSITY   (Turkey)

Author keywords

ABT 737; Anticancer; Apoptosis; Bcl 2; BH3 mimetic; Cancer; Gossypol; Obatoclax; Small molecule inhibitor

Indexed keywords

2 AMINO 6 BROMO 4 (1 CYANO 2 ETHOXY 2 OXOETHYL) 4H CHROMENE 3 CARBOXYLIC ACID ETHYL ESTER; 4 (4 FLUOROPHENYL) 2 (4 HYDROXYPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; 4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 NITROBENZENESULFONYL]BENZAMIDE; ANTIMYCIN A1; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; BH3 PROTEIN; BORTEZOMIB; CARBOPLATIN; CHELERYTHRINE; CHLORAMBUCIL; CISPLATIN; CYTARABINE; DEXAMETHASONE; ETOPOSIDE; FAS LIGAND; FLUDARABINE; GEMCITABINE; GENISTEIN; GOSSYPOL; GOSSYPOL DERIVATIVE; IMATINIB; IRINOTECAN; ISOSORBIDE; OBATOCLAX; PACLITAXEL; PICTRELISIB; PROTEIN BCL 2; PROTEIN MCL 1; PROTEIN TYROSINE KINASE; RAPAMYCIN; STAUROSPORINE; TOPOTECAN; TW 37; UNCLASSIFIED DRUG; UNINDEXED DRUG; VORINOSTAT; YC 137;

ARTICLE; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CELL DEATH; COLORECTAL CANCER; DIGESTIVE SYSTEM CANCER; DNA SYNTHESIS; ENZYME ACTIVITY; GASTROINTESTINAL TOXICITY; HEMATOLOGIC MALIGNANCY; HUMAN; LEUKEMIA; LIVER CANCER; LUNG CANCER; LUNG NON SMALL CELL CANCER; LUNG SMALL CELL CANCER; LYMPHOMA; MELANOMA; MITOSIS; MYELOMA; MYELOPROLIFERATIVE NEOPLASM; NEOPLASM; NONHUMAN; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROSTATE CANCER; PROTEIN PROTEIN INTERACTION; SOLID TUMOR; TOXICITY; TUMOR CELL; VESICULAR STOMATITIS VIRUS;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CLINICAL TRIALS AS TOPIC; GOSSYPOL; HUMANS; MODELS, BIOLOGICAL; MOLECULAR MIMICRY; NEOPLASMS; PROTO-ONCOGENE PROTEINS C-BCL-2; PYRROLES;

EID: 84860508708     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986712800099839     Document Type: Article

References (173)

1. Vogler, M.; Dinsdale, D.; Dyer, M. J.; Cohen, G. M. Bcl-2 inhibitors: small molecules with a big impact on cancer therapy. Cell Death Differ, 2009, 16(3), 360-7.
2. Oltersdorf, T.; Elmore, S. W.; Shoemaker, A. R.; Armstrong, R. C.; Augeri, D. J.; Belli, B. A.; Bruncko, M.; Deckwerth, T. L.; Dinges, J.; Hajduk, P. J.; Joseph, M. K.; Kitada, S.; Korsmeyer, S. J.; Kunzer, A. R.; Letai, A.; Li, C.; Mitten, M. J.; Nettesheim, D. G.; Ng, S.; Nimmer, P. M.; O'Connor, J. M.; Oleksijew, A.; Petros, A. M.; Reed, J. C.; Shen, W.; Tahir, S. K.; Thompson, C. B.; Tomaselli, K. J.; Wang, B.; Wendt, M. D.; Zhang, H.; Fesik, S. W.; Rosenberg, S. H. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature, 2005, 435(7042), 677-81. (Pubitemid 40825512)
3. Galsky, M. D.; Vogelzang, N. J. Docetaxel-based combination therapy for castration-resistant prostate cancer. Ann Oncol, 2010, 21(11), 2135-44.
4. Kang, M. H.; Reynolds, C. P. Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res, 2009, 15(4), 1126-32.
5. Labi, V.; Grespi, F.; Baumgartner, F.; Villunger, A. Targeting the Bcl-2-regulated apoptosis pathway by BH3 mimetics: a breakthrough in anticancer therapy? Cell Death Differ, 2008, 15(6), 977-87. (Pubitemid 351712602)
6. Kutuk, O.; Basaga, H. Bcl-2 protein family: implications in vascular apoptosis and atherosclerosis. Apoptosis, 2006, 11(10), 1661-75. (Pubitemid 44371045)
7. Arnold, A. A.; Aboukameel, A.; Chen, J.; Yang, D.; Wang, S.; Al-Katib, A.; Mohammad, R. M. Preclinical studies of Apogossypolone: a new nonpeptidic pan small-molecule inhibitor of Bcl-2, Bcl-XL and Mcl-1 proteins in Follicular Small Cleaved Cell Lymphoma model. Mol Cancer, 2008, 7, 20.
8. Tzung, S. P.; Kim, K. M.; Basanez, G.; Giedt, C. D.; Simon, J.; Zimmerberg, J.; Zhang, K. Y.; Hockenbery, D. M. Antimycin A mimics a cell-deathinducing Bcl-2 homology domain 3. Nat Cell Biol, 2001, 3(2), 183-91. (Pubitemid 32118372)
9. Willis, S. N.; Fletcher, J. I.; Kaufmann, T.; van Delft, M. F.; Chen, L.; Czabotar, P. E.; Ierino, H.; Lee, E. F.; Fairlie, W. D.; Bouillet, P.; Strasser, A.; Kluck, R. M.; Adams, J. M.; Huang, D. C. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science, 2007, 315(5813), 856-9.
10. Milanesi, E.; Costantini, P.; Gambalunga, A.; Colonna, R.; Petronilli, V.; Cabrelle, A.; Semenzato, G.; Cesura, A. M.; Pinard, E.; Bernardi, P. The mitochondrial effects of small organic ligands of BCL-2: sensitization of BCL-2-overexpressing cells to apoptosis by a pyrimidine-2, 4, 6-trione derivative. J Biol Chem, 2006, 281(15), 10066-72. (Pubitemid 43864541)
11. Vogler, M.; Dinsdale, D.; Sun, X. M.; Young, K. W.; Butterworth, M.; Nicotera, P.; Dyer, M. J.; Cohen, G. M. A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells. Cell Death Differ, 2008, 15(5), 820-30. (Pubitemid 351524424)
12. Maiuri, M. C.; Criollo, A.; Tasdemir, E.; Vicencio, J. M.; Tajeddine, N.; Hickman, J. A.; Geneste, O.; Kroemer, G. BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X (L). Autophagy, 2007, 3(4), 374-6. (Pubitemid 46986348)
13. Song, J. H.; Kandasamy, K.; Zemskova, M.; Lin, Y. W.; Kraft, A. S. The BH3 mimetic ABT-737 induces cancer cell senescence. Cancer Res, 2011, 71(2), 506-15.
14. Huang, S.; Sinicrope, F. A. Celecoxib-induced apoptosis is enhanced by ABT-737 and by inhibition of autophagy in human colorectal cancer cells. Autophagy, 2010, 6(2), 256-69.
15. McCoy, F.; Hurwitz, J.; McTavish, N.; Paul, I.; Barnes, C.; O'Hagan, B.; Odrzywol, K.; Murray, J.; Longley, D.; McKerr, G.; Fennell, D. A. Obatoclax induces Atg7-dependent autophagy independent of beclin-1 and BAX/BAK. Cell Death Dis, 2010, 1, e108.
16. Furuya, N.; Yu, J.; Byfield, M.; Pattingre, S.; Levine, B. The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy, 2005, 1(1), 46-52.
17. Maiuri, M. C.; Zalckvar, E.; Kimchi, A.; Kroemer, G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol, 2007, 8(9), 741-52. (Pubitemid 47312826)
18. Levine, B.; Kroemer, G. Autophagy in the pathogenesis of disease. Cell, 2008, 132(1), 27-42.
19. Pan, J.; Cheng, C.; Verstovsek, S.; Chen, Q.; Jin, Y.; Cao, Q. The BH3-mimetic GX15-070 induces autophagy, potentiates the cytotoxicity of carboplatin and 5-fluorouracil in esophageal carcinoma cells. Cancer Lett, 2010, 293(2), 167-74.
20. Karl, E.; Warner, K.; Zeitlin, B.; Kaneko, T.; Wurtzel, L.; Jin, T.; Chang, J.; Wang, S.; Wang, C. Y.; Strieter, R. M.; Nunez, G.; Polverini, P. J.; Nor, J. E. Bcl-2 acts in a proangiogenic signaling pathway through nuclear factorkappaB and CXC chemokines. Cancer Res, 2005, 65(12), 5063-9. (Pubitemid 40827314)
21. Wang, Z.; Song, W.; Aboukameel, A.; Mohammad, M.; Wang, G.; Banerjee, S.; Kong, D.; Wang, S.; Sarkar, F. H.; Mohammad, R. M. TW-37, a smallmolecule inhibitor of Bcl-2, inhibits cell growth and invasion in pancreatic cancer. Int J Cancer, 2008, 123(4), 958-66. (Pubitemid 352032427)
22. Wang, J. L.; Liu, D.; Zhang, Z. J.; Shan, S.; Han, X.; Srinivasula, S. M.; Croce, C. M.; Alnemri, E. S.; Huang, Z. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc Natl Acad Sci U S A, 2000, 97(13), 7124-9. (Pubitemid 30431428)
23. Chen, J.; Freeman, A.; Liu, J.; Dai, Q.; Lee, R. M. The apoptotic effect of HA14-1, a Bcl-2-interacting small molecular compound, requires Bax translocation and is enhanced by PK11195. Mol Cancer Ther, 2002, 1(12), 961-7.
24. Skommer, J.; Wlodkowic, D.; Matto, M.; Eray, M.; Pelkonen, J. HA14-1, a small molecule Bcl-2 antagonist, induces apoptosis and modulates action of selected anticancer drugs in follicular lymphoma B cells. Leuk Res, 2006, 30(3), 322-31. (Pubitemid 43053228)
25. Oliver, L.; Mahe, B.; Gree, R.; Vallette, F. M.; Juin, P. HA14-1, a small molecule inhibitor of Bcl-2, bypasses chemoresistance in leukaemia cells. Leuk Res, 2007, 31(6), 859-63. (Pubitemid 46855902)
26. Kessel, D.; Reiners, J. J., Jr. Initiation of apoptosis and autophagy by the Bcl-2 antagonist HA14-1. Cancer Lett, 2007, 249(2), 294-9. (Pubitemid 46452936)
27. Weyland, M.; Manero, F.; Paillard, A.; Gree, D.; Viault, G.; Jarnet, D.; Menei, P.; Juin, P.; Chourpa, I.; Benoit, J. P.; Gree, R.; Garcion, E. Mitochondrial targeting by use of lipid nanocapsules loaded with SV30, an analogue of the small-molecule Bcl-2 inhibitor HA14-1. J Control Release, 2011, 151(1), 74-82.
28. Hermanson, D.; Addo, S. N.; Bajer, A. A.; Marchant, J. S.; Das, S. G.; Srinivasan, B.; Al-Mousa, F.; Michelangeli, F.; Thomas, D. D.; Lebien, T. W.; Xing, C. Dual mechanisms of sHA 14-1 in inducing cell death through endoplasmic reticulum and mitochondria. Mol Pharmacol, 2009, 76(3), 667-78.
29. Tian, D.; Das, S. G.; Doshi, J. M.; Peng, J.; Lin, J.; Xing, C. sHA 14-1, a stable and ROS-free antagonist against anti-apoptotic Bcl-2 proteins, bypasses drug resistances and synergizes cancer therapies in human leukemia cell. Cancer Lett, 2008, 259(2), 198-208. (Pubitemid 350251643)
30. Gree, D.; Vorin, S.; Manthati, V. L.; Caijo, F.; Viault, G.; Manero, F.; Juin, P.; Gree, R. The synthesis of new, selected analogues of the pro-apoptotic and anticancer molecule HA 14-1. Tetrahedron Lett, 2008, 49(20), 3276-3278.
31. Tumilasci, V. F.; Oliere, S.; Nguyen, T. L.; Shamy, A.; Bell, J.; Hiscott, J. Targeting the apoptotic pathway with BCL-2 inhibitors sensitizes primary chronic lymphocytic leukemia cells to vesicular stomatitis virus-induced oncolysis. J Virol, 2008, 82(17), 8487-99.
32. Vogler, M.; Weber, K.; Dinsdale, D.; Schmitz, I.; Schulze-Osthoff, K.; Dyer, M. J.; Cohen, G. M. Different forms of cell death induced by putative BCL2 inhibitors. Cell Death Differ, 2009, 16(7), 1030-9.
33. Degterev, A.; Lugovskoy, A.; Cardone, 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(2), 173-82. (Pubitemid 32118371)
34. Wang, G.; Nikolovska-Coleska, Z.; Yang, C. Y.; Wang, R.; Tang, G.; Guo, J.; Shangary, S.; Qiu, S.; Gao, W.; Yang, D.; Meagher, J.; Stuckey, J.; Krajewski, K.; Jiang, S.; Roller, P. P.; Abaan, H. O.; Tomita, Y.; Wang, S. Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins. J Med Chem, 2006, 49(21), 6139-42. (Pubitemid 44595187)
35. Wei, J.; Stebbins, J. L.; Kitada, S.; Dash, R.; Placzek, W.; Rega, M. F.; Wu, B.; Cellitti, J.; Zhai, D.; Yang, L.; Dahl, R.; Fisher, P. B.; Reed, J. C.; Pellecchia, M. BI-97C1, an optically pure Apogossypol derivative as panactive inhibitor of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins. J Med Chem, 2010, 53(10), 4166-76.
36. Chan, S. L.; Lee, M. C.; Tan, K. O.; Yang, L. K.; Lee, A. S.; Flotow, H.; Fu, N. Y.; Butler, M. S.; Soejarto, D. D.; Buss, A. D.; Yu, V. C. Identification of chelerythrine as an inhibitor of BclXL function. J Biol Chem, 2003, 278(23), 20453-6. (Pubitemid 36806340)
37. Real, P. J.; Cao, Y.; Wang, R.; Nikolovska-Coleska, Z.; Sanz-Ortiz, J.; Wang, S.; Fernandez-Luna, J. L. Breast cancer cells can evade apoptosismediated selective killing by a novel small molecule inhibitor of Bcl-2. Cancer Res, 2004, 64(21), 7947-53. (Pubitemid 39446928)
38. Shore, G. C.; Viallet, J. Modulating the bcl-2 family of apoptosis suppressors for potential therapeutic benefit in cancer. Hematology Am Soc Hematol Educ Program, 2005, 226-30.
39. Zhang, Z.; Song, T.; Zhang, T.; Gao, J.; Wu, G.; An, L.; Du, G. A novel BH3 mimetic S1 potently induces Bax/Bak-dependent apoptosis by targeting both Bcl-2 and Mcl-1. Int J Cancer, 2011, 128(7), 1724-35.
40. Zhai, D.; Jin, C.; Satterthwait, A. C.; Reed, J. C. Comparison of chemical inhibitors of antiapoptotic Bcl-2-family proteins. Cell Death Differ, 2006, 13(8), 1419-21. (Pubitemid 44057478)
41. Schwartz, P. S.; Manion, M. K.; Emerson, C. B.; Fry, J. S.; Schulz, C. M.; Sweet, I. R.; Hockenbery, D. M. 2-Methoxy antimycin reveals a unique mechanism for Bcl-x (L) inhibition. Mol Cancer Ther, 2007, 6(7), 2073-80. (Pubitemid 47052498)
42. Cao, X.; Rodarte, C.; Zhang, L.; Morgan, C. D.; Littlejohn, J.; Smythe, W. R. Bcl2/bcl-xL inhibitor engenders apoptosis and increases chemosensitivity in mesothelioma. Cancer Biol Ther, 2007, 6(2), 246-52. (Pubitemid 46641630)
43. High, L. M.; Szymanska, B.; Wilczynska-Kalak, U.; Barber, N.; O'Brien, R.; Khaw, S. L.; Vikstrom, I. B.; Roberts, A. W.; Lock, R. B. The Bcl-2 homology domain 3 mimetic ABT-737 targets the apoptotic machinery in acute lymphoblastic leukemia resulting in synergistic in vitro and in vivo interactions with established drugs. Mol Pharmacol, 2010, 77(3), 483-94.
44. Witham, J.; Valenti, M. R.; De-Haven-Brandon, A. K.; Vidot, S.; Eccles, S. A.; Kaye, S. B.; Richardson, A. The Bcl-2/Bcl-XL family inhibitor ABT-737 sensitizes ovarian cancer cells to carboplatin. Clin Cancer Res, 2007, 13(23), 7191-8. (Pubitemid 350276906)
45. Wang, Z.; Goulet, R., 3rd; Stanton, K. J.; Sadaria, M.; Nakshatri, H. Differential effect of anti-apoptotic genes Bcl-xL and c-FLIP on sensitivity of MCF-7 breast cancer cells to paclitaxel and docetaxel. Anticancer Res, 2005, 25(3c), 2367-79. (Pubitemid 41044718)
46. Huerta-Yepez, S.; Vega, M.; Jazirehi, A.; Garban, H.; Hongo, F.; Cheng, G.; Bonavida, B. Nitric oxide sensitizes prostate carcinoma cell lines to TRAILmediated apoptosis via inactivation of NF-kappa B and inhibition of Bcl-xl expression. Oncogene, 2004, 23(29), 4993-5003. (Pubitemid 38938732)
47. Lickliter, J. D.; Wood, N. J.; Johnson, L.; McHugh, G.; Tan, J.; Wood, F.; Cox, J.; Wickham, N. W. HA14-1 selectively induces apoptosis in Bcl-2-overexpressing leukemia/lymphoma cells, and enhances cytarabine-induced cell death. Leukemia, 2003, 17(11), 2074-80. (Pubitemid 37428370)
48. Simonin, K.; Brotin, E.; Dufort, S.; Dutoit, S.; Goux, D.; N'Diaye, M.; Denoyelle, C.; Gauduchon, P.; Poulain, L. Mcl-1 is an important determinant of the apoptotic response to the BH3-mimetic molecule HA14-1 in cisplatinresistant ovarian carcinoma cells. Mol Cancer Ther, 2009, 8(11), 3162-70.
49. An, J.; Chervin, A. S.; Nie, A.; Ducoff, H. S.; Huang, Z. Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor. Oncogene, 2007, 26(5), 652-61. (Pubitemid 46204245)
50. Hetschko, H.; Voss, V.; Horn, S.; Seifert, V.; Prehn, J. H.; Kogel, D. Pharmacological inhibition of Bcl-2 family members reactivates TRAILinduced apoptosis in malignant glioma. J Neurooncol, 2008, 86(3), 265-72.
51. Paoluzzi, L.; Gonen, M.; Gardner, J. R.; Mastrella, J.; Yang, D.; Holmlund, J.; Sorensen, M.; Leopold, L.; Manova, K.; Marcucci, G.; Heaney, M. L.; O'Connor, O. A. Targeting Bcl-2 family members with the BH3 mimetic AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma. Blood, 2008, 111(11), 5350-8.
52. Balakrishnan, K.; Burger, J. A.; Wierda, W. G.; Gandhi, V. AT-101 induces apoptosis in CLL B cells and overcomes stromal cell-mediated Mcl-1 induction and drug resistance. Blood, 2009, 113(1), 149-53.
53. Kline, M. P.; Rajkumar, S. V.; Timm, M. M.; Kimlinger, T. K.; Haug, J. L.; Lust, J. A.; Greipp, P. R.; Kumar, S. R-(-)-gossypol (AT-101) activates programmed cell death in multiple myeloma cells. Exp Hematol, 2008, 36(5), 568-76.
54. McGregor, N.; Patel, L.; Craig, M.; Weidner, S.; Wang, S.; Pienta, K. J. AT-101 (R-(-)-gossypol acetic acid) enhances the effectiveness of androgen deprivation therapy in the VCaP prostate cancer model. J Cell Biochem, 2010, 110(5), 1187-94.
55. Loberg, R. D.; McGregor, N.; Ying, C.; Sargent, E.; Pienta, K. J. In vivo evaluation of AT-101 (R-(-)-gossypol acetic acid) in androgen-independent growth of VCaP prostate cancer cells in combination with surgical castration. Neoplasia, 2007, 9(12), 1030-7. (Pubitemid 350255351)
56. Mohammad, R. M.; Wang, S.; Aboukameel, A.; Chen, B.; Wu, X.; Chen, J.; Al-Katib, A. Preclinical studies of a nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-X (L) [(-)-gossypol] against diffuse large cell lymphoma. Mol Cancer Ther, 2005, 4(1), 13-21. (Pubitemid 40268062)
57. Zhang, M.; Liu, H.; Guo, R.; Ling, Y.; Wu, X.; Li, B.; Roller, P. P.; Wang, S.; Yang, D. Molecular mechanism of gossypol-induced cell growth inhibition and cell death of HT-29 human colon carcinoma cells. Biochem Pharmacol, 2003, 66(1), 93-103. (Pubitemid 36724903)
58. Wolter, K. G.; Wang, S. J.; Henson, B. S.; Wang, S.; Griffith, K. A.; Kumar, B.; Chen, J.; Carey, T. E.; Bradford, C. R.; D'Silva, N. J. (-)-gossypol inhibits growth and promotes apoptosis of human head and neck squamous cell carcinoma in vivo. Neoplasia, 2006, 8(3), 163-72. (Pubitemid 43671231)
59. Xu, L.; Yang, D.; Wang, S.; Tang, W.; Liu, M.; Davis, M.; Chen, J.; Rae, J. M.; Lawrence, T.; Lippman, M. E. (-)-Gossypol enhances response to radiation therapy and results in tumor regression of human prostate cancer. Mol Cancer Ther, 2005, 4(2), 197-205. (Pubitemid 40340199)
60. Bauer, J. A.; Trask, D. K.; Kumar, B.; Los, G.; Castro, J.; Lee, J. S.; Chen, J.; Wang, S.; Bradford, C. R.; Carey, T. E. Reversal of cisplatin resistance with a BH3 mimetic, (-)-gossypol, in head and neck cancer cells: role of wild-type p53 and Bcl-xL. Mol Cancer Ther, 2005, 4(7), 1096-104. (Pubitemid 41079103)
61. Al-Katib, A. M.; Sun, Y.; Goustin, A. S.; Azmi, A. S.; Chen, B.; Aboukameel, A.; Mohammad, R. M. SMI of Bcl-2 TW-37 is active across a spectrum of B-cell tumors irrespective of their proliferative and differentiation status. J Hematol Oncol, 2009, 2, 8.
62. Mohammad, R. M.; Goustin, A. S.; Aboukameel, A.; Chen, B.; Banerjee, S.; Wang, G.; Nikolovska-Coleska, Z.; Wang, S.; Al-Katib, A. Preclinical studies of TW-37, a new nonpeptidic small-molecule inhibitor of Bcl-2, in diffuse large cell lymphoma xenograft model reveal drug action on both Bcl-2 and Mcl-1. Clin Cancer Res, 2007, 13(7), 2226-35. (Pubitemid 46649892)
63. Azmi, A. S.; Wang, Z.; Burikhanov, R.; Rangnekar, V. M.; Wang, G.; Chen, J.; Wang, S.; Sarkar, F. H.; Mohammad, R. M. Critical role of prostate apoptosis response-4 in determining the sensitivity of pancreatic cancer cells to small-molecule inhibitor-induced apoptosis. Mol Cancer Ther, 2008, 7(9), 2884-93.
64. Ashimori, N.; Zeitlin, B. D.; Zhang, Z.; Warner, K.; Turkienicz, I. M.; Spalding, A. C.; Teknos, T. N.; Wang, S.; Nor, J. E. TW-37, a smallmolecule inhibitor of Bcl-2, mediates S-phase cell cycle arrest and suppresses head and neck tumor angiogenesis. Mol Cancer Ther, 2009, 8(4), 893-903.
65. Sun, Y.; Wu, J.; Aboukameel, A.; Banerjee, S.; Arnold, A. A.; Chen, J.; Nikolovska-Coleska, Z.; Lin, Y.; Ling, X.; Yang, D.; Wang, S.; Al-Katib, A.; Mohammad, R. M. Apogossypolone, a nonpeptidic small molecule inhibitor targeting Bcl-2 family proteins, effectively inhibits growth of diffuse large cell lymphoma cells in vitro and in vivo. Cancer Biol Ther, 2008, 7(9), 1418-26.
66. Sun, J.; Li, Z. M.; Hu, Z. Y.; Lin, X. B.; Zhou, N. N.; Xian, L. J.; Yang, D. J.; Jiang, W. Q. ApoG2 inhibits antiapoptotic Bcl-2 family proteins and induces mitochondria-dependent apoptosis in human lymphoma U937 cells. Anticancer Drugs, 2008, 19(10), 967-74.
67. Mi, J. X.; Wang, G. F.; Wang, H. B.; Sun, X. Q.; Ni, X. Y.; Zhang, X. W.; Tang, J. M.; Yang, D. J. Synergistic antitumoral activity and induction of apoptosis by novel pan Bcl-2 proteins inhibitor apogossypolone with adriamycin in human hepatocellular carcinoma. Acta Pharmacol Sin, 2008, 29(12), 1467-77.
68. Hu, Z. Y.; Sun, J.; Zhu, X. F.; Yang, D.; Zeng, Y. X. ApoG2 induces cell cycle arrest of nasopharyngeal carcinoma cells by suppressing the c-Myc signaling pathway. J Transl Med, 2009, 7, 74.
69. Wei, J.; Kitada, S.; Stebbins, J. L.; Placzek, W.; Zhai, D.; Wu, B.; Rega, M. F.; Zhang, Z.; Cellitti, J.; Yang, L.; Dahl, R.; Reed, J. C.; Pellecchia, M. Synthesis and biological evaluation of Apogossypolone derivatives as panactive inhibitors of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins. J Med Chem, 2010, 53(22), 8000-11.
70. Kaminskyy, V.; Kulachkovskyy, O.; Stoika, R. A decisive role of mitochondria in defining rate and intensity of apoptosis induction by different alkaloids. Toxicol Lett, 2008, 177(3), 168-81.
71. Zhang, Z. F.; Guo, Y.; Zhang, J. B.; Wei, X. H. Induction of apoptosis by chelerythrine chloride through mitochondrial pathway and Bcl-2 family proteins in human hepatoma SMMC-7721 cell. Arch Pharm Res, 2011, 34(5), 791-800.
72. Funakoshi, T.; Aki, T.; Nakayama, H.; Watanuki, Y.; Imori, S.; Uemura, K. Reactive oxygen species-independent rapid initiation of mitochondrial apoptotic pathway by chelerythrine. Toxicol In Vitro, 2011, 25(8), 1581-7.
73. Perez-Galan, P.; Roue, G.; Villamor, N.; Campo, E.; Colomer, D. The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by enhancing Noxa-mediated activation of Bak. Blood, 2007, 109(10), 4441-9. (Pubitemid 46743414)
74. Brem, E. A.; Thudium, K.; Khubchandani, S.; Tsai, P. C.; Olejniczak, S. H.; Bhat, S.; Riaz, W.; Gu, J.; Iqbal, A.; Campagna, R.; Knight, J.; Mavis, C.; Hoskin, P.; Deeb, G.; Gibbs, J. F.; Fetterly, G.; Czuczman, M. S.; Hernandez-Ilizaliturri, F. J. Distinct cellular and therapeutic effects of obatoclax in rituximab-sensitive and -resistant lymphomas. Br J Haematol, 2011, 153(5), 599-611.
75. Konopleva, M.; Watt, J.; Contractor, R.; Tsao, T.; Harris, D.; Estrov, Z.; Bornmann, W.; Kantarjian, H.; Viallet, J.; Samudio, I.; Andreeff, M. Mechanisms of antileukemic activity of the novel Bcl-2 homology domain-3 mimetic GX15-070 (obatoclax). Cancer Res, 2008, 68(9), 3413-20.
76. Heidari, N.; Hicks, M. A.; Harada, H. GX15-070 (obatoclax) overcomes glucocorticoid resistance in acute lymphoblastic leukemia through induction of apoptosis and autophagy. Cell Death Dis, 2010, 1, e76.
77. Trudel, S.; Li, Z. H.; Rauw, J.; Tiedemann, R. E.; Wen, X. Y.; Stewart, A. K. Preclinical studies of the pan-Bcl inhibitor obatoclax (GX015-070) in multiple myeloma. Blood, 2007, 109(12), 5430-8. (Pubitemid 46890566)
78. Li, J.; Viallet, J.; Haura, E. B. A small molecule pan-Bcl-2 family inhibitor, GX15-070, induces apoptosis and enhances cisplatin-induced apoptosis in non-small cell lung cancer cells. Cancer Chemother Pharmacol, 2008, 61(3), 525-34. (Pubitemid 350275989)
79. Crawford, N.; Chacko, A. D.; Savage, K. I.; McCoy, F.; Redmond, K.; Longley, D. B.; Fennell, D. A. Platinum resistant cancer cells conserve sensitivity to BH3 domains and obatoclax induced mitochondrial apoptosis. Apoptosis, 2011, 16(3), 311-20.
80. Nguyen, M.; Marcellus, R. C.; Roulston, A.; Watson, M.; Serfass, L.; Murthy Madiraju, S. R.; Goulet, D.; Viallet, J.; Belec, L.; Billot, X.; Acoca, S.; Purisima, E.; Wiegmans, A.; Cluse, L.; Johnstone, R. W.; Beauparlant, P.; Shore, G. C. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc Natl Acad Sci U S A, 2007, 104(49), 19512-7.
81. Mott, J. L.; Bronk, S. F.; Mesa, R. A.; Kaufmann, S. H.; Gores, G. J. BH3-only protein mimetic obatoclax sensitizes cholangiocarcinoma cells to Apo2L/TRAIL-induced apoptosis. Mol Cancer Ther, 2008, 7(8), 2339-47.
82. Jiang, C. C.; Wroblewski, D.; Yang, F.; Hersey, P.; Zhang, X. D. Human melanoma cells under endoplasmic reticulum stress are more susceptible to apoptosis induced by the BH3 mimetic obatoclax. Neoplasia, 2009, 11(9), 945-55.
83. Mason, K. D.; Vandenberg, C. J.; Scott, C. L.; Wei, A. H.; Cory, S.; Huang, D. C.; Roberts, A. W. In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas. Proc Natl Acad Sci U S A, 2008, 105(46), 17961-6.
84. Jayanthan, A.; Howard, S. C.; Trippett, T.; Horton, T.; Whitlock, J. A.; Daisley, L.; Lewis, V.; Narendran, A. Targeting the Bcl-2 family of proteins in Hodgkin lymphoma: in vitro cytotoxicity, target modulation and drug combination studies of the Bcl-2 homology 3 mimetic ABT-737. Leuk Lymphoma, 2009, 50(7), 1174-82.
85. Konopleva, M.; Contractor, R.; Tsao, T.; Samudio, I.; Ruvolo, P. P.; Kitada, S.; Deng, X.; Zhai, D.; Shi, Y. X.; Sneed, T.; Verhaegen, M.; Soengas, M.; Ruvolo, V. R.; McQueen, T.; Schober, W. D.; Watt, J. C.; Jiffar, T.; Ling, X.; Marini, F. C.; Harris, D.; Dietrich, M.; Estrov, Z.; McCubrey, J.; May, W. S.; Reed, J. C.; Andreeff, M. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell, 2006, 10(5), 375-88. (Pubitemid 44693472)
86. Kuroda, J.; Kimura, S.; Andreeff, M.; Ashihara, E.; Kamitsuji, Y.; Yokota, A.; Kawata, E.; Takeuchi, M.; Tanaka, R.; Murotani, Y.; Matsumoto, Y.; Tanaka, H.; Strasser, A.; Taniwaki, M.; Maekawa, T. ABT-737 is a useful component of combinatory chemotherapies for chronic myeloid leukaemias with diverse drug-resistance mechanisms. Br J Haematol, 2008, 140(2), 181-90. (Pubitemid 350265045)
87. Vogler, M.; Butterworth, M.; Majid, A.; Walewska, R. J.; Sun, X. M.; Dyer, M. J.; Cohen, G. M. Concurrent up-regulation of BCL-XL and BCL2A1 induces approximately 1000-fold resistance to ABT-737 in chronic lymphocytic leukemia. Blood, 2009, 113(18), 4403-13.
88. Mason, K. D.; Khaw, S. L.; Rayeroux, K. C.; Chew, E.; Lee, E. F.; Fairlie, W. D.; Grigg, A. P.; Seymour, J. F.; Szer, J.; Huang, D. C.; Roberts, A. W. The BH3 mimetic compound, ABT-737, synergizes with a range of cytotoxic chemotherapy agents in chronic lymphocytic leukemia. Leukemia, 2009, 23(11), 2034-41.
89. Lock, R.; Carol, H.; Houghton, P. J.; Morton, C. L.; Kolb, E. A.; Gorlick, R.; Reynolds, C. P.; Maris, J. M.; Keir, S. T.; Wu, J.; Smith, M. A. Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr Blood Cancer, 2008, 50(6), 1181-9. (Pubitemid 351555542)
90. Tse, C.; Shoemaker, A. R.; Adickes, J.; Anderson, M. G.; Chen, J.; Jin, S.; Johnson, E. F.; Marsh, K. C.; Mitten, M. J.; Nimmer, P.; Roberts, L.; Tahir, S. K.; Xiao, Y.; Yang, X.; Zhang, H.; Fesik, S.; Rosenberg, S. H.; Elmore, S. W. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res, 2008, 68(9), 3421-8.
91. Kline, M. P.; Rajkumar, S. V.; Timm, M. M.; Kimlinger, T. K.; Haug, J. L.; Lust, J. A.; Greipp, P. R.; Kumar, S. ABT-737, an inhibitor of Bcl-2 family proteins, is a potent inducer of apoptosis in multiple myeloma cells. Leukemia, 2007, 21(7), 1549-60. (Pubitemid 46965297)
92. Paoluzzi, L.; Gonen, M.; Bhagat, G.; Furman, R. R.; Gardner, J. R.; Scotto, L.; Gueorguiev, V. D.; Heaney, M. L.; Manova, K.; O'Connor, O. A. The BH3-only mimetic ABT-737 synergizes the antineoplastic activity of proteasome inhibitors in lymphoid malignancies. Blood, 2008, 112(7), 2906-16.
93. Tahir, S. K.; Yang, X.; Anderson, M. G.; Morgan-Lappe, S. E.; Sarthy, A. V.; Chen, J.; Warner, R. B.; Ng, S. C.; Fesik, S. W.; Elmore, S. W.; Rosenberg, S. H.; Tse, C. Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737. Cancer Res, 2007, 67(3), 1176-83.
94. Hann, C. L.; Daniel, V. C.; Sugar, E. A.; Dobromilskaya, I.; Murphy, S. C.; Cope, L.; Lin, X.; Hierman, J. S.; Wilburn, D. L.; Watkins, D. N.; Rudin, C. M. Therapeutic efficacy of ABT-737, a selective inhibitor of BCL-2, in small cell lung cancer. Cancer Res, 2008, 68(7), 2321-8. (Pubitemid 351521806)
95. Micha, D.; Cummings, J.; Shoemaker, A.; Elmore, S.; Foster, K.; Greaves, M.; Ward, T.; Rosenberg, S.; Dive, C.; Simpson, K. Circulating biomarkers of cell death after treatment with the BH-3 mimetic ABT-737 in a preclinical model of small-cell lung cancer. Clin Cancer Res, 2008, 14(22), 7304-10.
96. Shoemaker, A. R.; Mitten, M. J.; Adickes, J.; Ackler, S.; Refici, M.; Ferguson, D.; Oleksijew, A.; O'Connor, J. M.; Wang, B.; Frost, D. J.; Bauch, J.; Marsh, K.; Tahir, S. K.; Yang, X.; Tse, C.; Fesik, S. W.; Rosenberg, S. H.; Elmore, S. W. Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models. Clin Cancer Res, 2008, 14(11), 3268-77.
97. Zall, H.; Weber, A.; Besch, R.; Zantl, N.; Hacker, G. Chemotherapeutic drugs sensitize human renal cell carcinoma cells to ABT-737 by a mechanism involving the Noxa-dependent inactivation of Mcl-1 or A1. Mol Cancer, 2010, 9, 164.
98. Li, R.; Zang, Y.; Li, C.; Patel, N. S.; Grandis, J. R.; Johnson, D. E. ABT-737 synergizes with chemotherapy to kill head and neck squamous cell carcinoma cells via a Noxa-mediated pathway. Mol Pharmacol, 2009, 75(5), 1231-9.
99. Huang, S.; Sinicrope, F. A. BH3 mimetic ABT-737 potentiates TRAILmediated apoptotic signaling by unsequestering Bim and Bak in human pancreatic cancer cells. Cancer Res, 2008, 68(8), 2944-51. (Pubitemid 351556295)
100. Okumura, K.; Huang, S.; Sinicrope, F. A. Induction of Noxa sensitizes human colorectal cancer cells expressing Mcl-1 to the small-molecule Bcl-2/Bcl-xL inhibitor, ABT-737. Clin Cancer Res, 2008, 14(24), 8132-42.
101. Reynoso, D.; Nolden, L. K.; Yang, D.; Dumont, S. N.; Conley, A. P.; Dumont, A. G.; Zhou, K.; Duensing, A.; Trent, J. C. Synergistic induction of apoptosis by the Bcl-2 inhibitor ABT-737 and imatinib mesylate in gastrointestinal stromal tumor cells. Mol Oncol, 2011, 5(1), 93-104.
102. Zhang, Z.; Jin, L.; Qian, X.; Wei, M.; Wang, Y.; Wang, J.; Yang, Y.; Xu, Q.; Xu, Y.; Liu, F. Novel Bcl-2 inhibitors: Discovery and mechanism study of small organic apoptosis-inducing agents. Chembiochem, 2007, 8(1), 113-21. (Pubitemid 46121578)
103. Zhang, Z.; Wu, G.; Gao, J.; Song, T. Inclusion complex of a Bcl-2 inhibitor with cyclodextrin: characterization, cellular accumulation, and in vivo antitumor activity. Mol Pharm, 2010, 7(4), 1348-54.
104. Kitada, S.; Leone, M.; Sareth, S.; Zhai, D.; Reed, J. C.; Pellecchia, M. Discovery, characterization, and structure-activity relationships studies of proapoptotic polyphenols targeting B-cell lymphocyte/leukemia-2 proteins. J Med Chem, 2003, 46(20), 4259-64. (Pubitemid 37153007)
105. Oliver, C. L.; Bauer, J. A.; Wolter, K. G.; Ubell, M. L.; Narayan, A.; O'Connell, K. M.; Fisher, S. G.; Wang, S.; Wu, X.; Ji, M.; Carey, T. E.; Bradford, C. R. In vitro effects of the BH3 mimetic, (-)-gossypol, on head and neck squamous cell carcinoma cells. Clin Cancer Res, 2004, 10(22), 7757-63. (Pubitemid 39557541)
106. Zeitlin, B. D.; Joo, E.; Dong, Z.; Warner, K.; Wang, G.; Nikolovska-Coleska, Z.; Wang, S.; Nor, J. E. Antiangiogenic effect of TW37, a small-molecule inhibitor of Bcl-2. Cancer Res, 2006, 66(17), 8698-706. (Pubitemid 44449186)
107. Sun, J.; Li, Z. M.; Hu, Z. Y.; Zeng, Z. L.; Yang, D. J.; Jiang, W. Q. Apogossypolone inhibits cell growth by inducing cell cycle arrest in U937 cells. Oncol Rep, 2009, 22(1), 193-8.
108. Gao, P.; Bauvy, C.; Souquere, S.; Tonelli, G.; Liu, L.; Zhu, Y.; Qiao, Z.; Bakula, D.; Proikas-Cezanne, T.; Pierron, G.; Codogno, P.; Chen, Q.; Mehrpour, M. The Bcl-2 homology domain 3 mimetic gossypol induces both Beclin 1-dependent and Beclin 1-independent cytoprotective autophagy in cancer cells. J Biol Chem, 2010, 285(33), 25570-81.
109. Buron, N.; Porceddu, M.; Brabant, M.; Desgue, D.; Racoeur, C.; Lassalle, M.; Pechoux, C.; Rustin, P.; Jacotot, E.; Borgne-Sanchez, A. Use of human cancer cell lines mitochondria to explore the mechanisms of BH3 peptides and ABT-737-induced mitochondrial membrane permeabilization. PLoS One, 2010, 5(3), e9924.
110. Pei, X. Y.; 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(10), 2036-45. (Pubitemid 37322135)
111. Manero, F.; Gautier, F.; Gallenne, T.; Cauquil, N.; Gree, D.; Cartron, P. F.; Geneste, O.; Gree, R.; Vallette, F. M.; Juin, P. The small organic compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells to induction of cell death. Cancer Res, 2006, 66(5), 2757-64.
112. Hamada, N.; Kataoka, K.; Sora, S.; Hara, T.; Omura-Minamisawa, M.; Funayama, T.; Sakashita, T.; Nakano, T.; Kobayashi, Y. The small-molecule Bcl-2 inhibitor HA14-1 sensitizes cervical cancer cells, but not normal fibroblasts, to heavy-ion radiation. Radiother Oncol, 2008, 89(2), 227-30.
113. Mohan, N.; Karmakar, S.; Choudhury, S. R.; Banik, N. L.; Ray, S. K. Bcl-2 inhibitor HA14-1 and genistein together adeptly down regulated survival factors and activated cysteine proteases for apoptosis in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells. Brain Res, 2009, 1283, 155-66.
114. Roa, W.; Chen, H.; Alexander, A.; Gulavita, S.; Thng, J.; Sun, X. J.; Petruk, K.; Moore, R. Enhancement of radiation sensitivity with BH3I-1 in nonsmall cell lung cancer. Clin Invest Med, 2005, 28(2), 55-63. (Pubitemid 40676848)
115. Amm, H. M.; Zhou, T.; Steg, A. D.; Kuo, H.; Li, Y.; Buchsbaum, D. J. Mechanisms of drug sensitization to TRA-8, an agonistic death receptor 5 antibody, involve modulation of the intrinsic apoptotic pathway in human breast cancer cells. Mol Cancer Res, 2011, 9(4), 403-17.
116. Mitsiades, C. S.; Hayden, P.; Kotoula, V.; McMillin, D. W.; McMullan, C.; Negri, J.; Delmore, J. E.; Poulaki, V.; Mitsiades, N. Bcl-2 overexpression in thyroid carcinoma cells increases sensitivity to Bcl-2 homology 3 domain inhibition. J Clin Endocrinol Metab, 2007, 92(12), 4845-52. (Pubitemid 350223468)
117. Ray, S.; Bucur, O.; Almasan, A. Sensitization of prostate carcinoma cells to Apo2L/TRAIL by a Bcl-2 family protein inhibitor. Apoptosis, 2005, 10(6), 1411-8. (Pubitemid 43117685)
118. Zerp, S. F.; Stoter, R.; Kuipers, G.; Yang, D.; Lippman, M. E.; van Blitterswijk, W. J.; Bartelink, H.; Rooswinkel, R.; Lafleur, V.; Verheij, M. AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members, activates the SAPK/JNK pathway and enhances radiation-induced apoptosis. Radiat Oncol, 2009, 4, 47.
119. Moretti, L.; Li, B.; Kim, K. W.; Chen, H.; Lu, B. AT-101, a pan-Bcl-2 inhibitor, leads to radiosensitization of non-small cell lung cancer. J Thorac Oncol, 2010, 5(5), 680-7.
120. Hanada, M.; Takasu, H.; Kitaura, M. Acquired resistance to miriplatin in rat hepatoma AH109A/MP10 is associated with increased Bcl-2 expression, leading to defects in inducing apoptosis. Oncol Rep, 2010, 24(4), 1011-8.
121. Crawford, A. C.; Riggins, R. B.; Shajahan, A. N.; Zwart, A.; Clarke, R. Coinhibition of BCL-W and BCL2 restores antiestrogen sensitivity through BECN1 and promotes an autophagy-associated necrosis. PLoS One, 2010, 5(1), e8604.
122. Samuel, S.; Tumilasci, V. F.; Oliere, S.; Nguyen, T. L.; Shamy, A.; Bell, J.; Hiscott, J. VSV oncolysis in combination with the BCL-2 inhibitor obatoclax overcomes apoptosis resistance in chronic lymphocytic leukemia. Mol Ther, 2010, 18(12), 2094-103.
123. Wei, Y.; Kadia, T.; Tong, W.; Zhang, M.; Jia, Y.; Yang, H.; Hu, Y.; Tambaro, F. P.; Viallet, J.; O'Brien, S.; Garcia-Manero, G. The combination of a histone deacetylase inhibitor with the Bcl-2 homology domain-3 mimetic GX15-070 has synergistic antileukemia activity by activating both apoptosis and autophagy. Clin Cancer Res, 2010, 16(15), 3923-32.
124. Huang, S.; Okumura, K.; Sinicrope, F. A. BH3 mimetic obatoclax enhances TRAIL-mediated apoptosis in human pancreatic cancer cells. Clin Cancer Res, 2009, 15(1), 150-9.
125. van Delft, M. F.; Wei, A. H.; Mason, K. D.; Vandenberg, C. J.; Chen, L.; Czabotar, P. E.; Willis, S. N.; Scott, C. L.; Day, C. L.; Cory, S.; Adams, J. M.; Roberts, A. W.; Huang, D. C. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell, 2006, 10(5), 389-99. (Pubitemid 44711953)
126. Ackler, S.; Mitten, M. J.; Foster, K.; Oleksijew, A.; Refici, M.; Tahir, S. K.; Xiao, Y.; Tse, C.; Frost, D. J.; Fesik, S. W.; Rosenberg, S. H.; Elmore, S. W.; Shoemaker, A. R. The Bcl-2 inhibitor ABT-263 enhances the response of multiple chemotherapeutic regimens in hematologic tumors in vivo. Cancer Chemother Pharmacol, 2010, 66(5), 869-80.
127. Kang, M. H.; Kang, Y. H.; Szymanska, B.; Wilczynska-Kalak, U.; Sheard, M. A.; Harned, T. M.; Lock, R. B.; Reynolds, C. P. Activity of vincristine, LASP, and dexamethasone against acute lymphoblastic leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo. Blood, 2007, 110(6), 2057-66. (Pubitemid 47443923)
128. Wiegmans, A. P.; Alsop, A. E.; Bots, M.; Cluse, L. A.; Williams, S. P.; Banks, K. M.; Ralli, R.; Scott, C. L.; Frenzel, A.; Villunger, A.; Johnstone, R. W. Deciphering the molecular events necessary for synergistic tumor cell apoptosis mediated by the histone deacetylase inhibitor vorinostat and the BH3 mimetic ABT-737. Cancer Res, 2011, 71(10), 3603-15.
129. Li, G.; Miskimen, K. L.; Wang, Z.; Xie, X. Y.; Tse, W.; Gouilleux, F.; Moriggl, R.; Bunting, K. D. Effective targeting of STAT5-mediated survival in myeloproliferative neoplasms using ABT-737 combined with rapamycin. Leukemia, 2010, 24(8), 1397-405.
130. Xu, H.; Krystal, G. W. Actinomycin D decreases Mcl-1 expression and acts synergistically with ABT-737 against small cell lung cancer cell lines. Clin Cancer Res, 2010, 16(17), 4392-400.
131. Zhang, C.; Cai, T. Y.; Zhu, H.; Yang, L. Q.; Jiang, H.; Dong, X. W.; Hu, Y. Z.; Lin, N. M.; He, Q. J.; Yang, B. Synergistic antitumor activity of gemcitabine and ABT-737 in vitro and in vivo through disrupting the interaction of USP9X and Mcl-1. Mol Cancer Ther, 2011, 10(7), 1264-75.
132. Tan, N.; Malek, M.; Zha, J.; Yue, P.; Kassees, R.; Berry, L.; Fairbrother, W. J.; Sampath, D.; Belmont, L. D. Navitoclax enhances the efficacy of taxanes in non-small cell lung cancer models. Clin Cancer Res, 2011, 17(6), 1394-404.
133. Chen, J.; Jin, S.; Abraham, V.; Huang, X.; Liu, B.; Mitten, M. J.; Nimmer, P.; Lin, X.; Smith, M.; Shen, Y.; Shoemaker, A. R.; Tahir, S. K.; Zhang, H.; Ackler, S. L.; Rosenberg, S. H.; Maecker, H.; Sampath, D.; Leverson, J. D.; Tse, C.; Elmore, S. W. The Bcl-2/Bcl-XL/Bcl-w Inhibitor, Navitoclax, Enhances the Activity of Chemotherapeutic Agents in vitro and in vivo. Mol Cancer Ther, 2011.
134. Weber, A.; Kirejczyk, Z.; Potthoff, S.; Ploner, C.; Hacker, G. Endogenous Noxa Determines the Strong Proapoptotic Synergism of the BH3-Mimetic ABT-737 with Chemotherapeutic Agents in Human Melanoma Cells. Transl Oncol, 2009, 2(2), 73-83.
135. Keuling, A. M.; Andrew, S. E.; Tron, V. A. Inhibition of p38 MAPK enhances ABT-737-induced cell death in melanoma cell lines: novel regulation of PUMA. Pigment Cell Melanoma Res, 2010, 23(3), 430-40.
136. Bhat, U. G.; Pandit, B.; Gartel, A. L. ARC synergizes with ABT-737 to induce apoptosis in human cancer cells. Mol Cancer Ther, 2010, 9(6), 1688-96.
137. Traini, R.; Ben-Josef, G.; Pastrana, D. V.; Moskatel, E.; Sharma, A. K.; Antignani, A.; Fitzgerald, D. J. ABT-737 overcomes resistance to immunotoxin-mediated apoptosis and enhances the delivery of pseudomonas exotoxin-based proteins to the cell cytosol. Mol Cancer Ther, 2010, 9(7), 2007-15.
138. Raats, D. A.; de Bruijn, M. T.; Steller, E. J.; Emmink, B. L.; Borel-Rinkes, I. H.; Kranenburg, O. Synergistic killing of colorectal cancer cells by oxaliplatin and ABT-737. Cell Oncol (Dordr), 2011, 34(4), 307-13.
139. Shi, J.; Zhou, Y.; Huang, H. C.; Mitchison, T. J. Navitoclax (ABT-263) accelerates apoptosis during drug-induced mitotic arrest by antagonizing BclxL. Cancer Res, 2011, 71(13), 4518-26.
140. Zheng, L.; Yang, W.; Zhang, C.; Ding, W. J.; Zhu, H.; Lin, N. M.; Wu, H. H.; He, Q. J.; Yang, B. GDC-0941 sensitizes breast cancer to ABT-737 in vitro and in vivo through promoting the degradation of Mcl-1. Cancer Lett, 2011, 309(1), 27-36.
141. Hikita, H.; Takehara, T.; Shimizu, S.; Kodama, T.; Shigekawa, M.; Iwase, K.; Hosui, A.; Miyagi, T.; Tatsumi, T.; Ishida, H.; Li, W.; Kanto, T.; Hiramatsu, N.; Hayashi, N. The Bcl-xL inhibitor, ABT-737, efficiently induces apoptosis and suppresses growth of hepatoma cells in combination with sorafenib. Hepatology, 2010, 52(4), 1310-21.
142. Smoot, R. L.; Blechacz, B. R.; Werneburg, N. W.; Bronk, S. F.; Sinicrope, F. A.; Sirica, A. E.; Gores, G. J. A Bax-mediated mechanism for obatoclaxinduced apoptosis of cholangiocarcinoma cells. Cancer Res, 2010, 70(5), 1960-9.
143. Olberding, K. E.; Wang, X. L.; Zhu, Y. L.; Pan, J. M.; Rai, S. N.; Li, C. Actinomycin D synergistically enhances the efficacy of the BH3 mimetic ABT-737 by downregulating Mcl-1 expression. Cancer Biology & Therapy, 2010, 10(9), 922-933.
144. Wang, Z.; Azmi, A. S.; Ahmad, A.; Banerjee, S.; Wang, S.; Sarkar, F. H.; Mohammad, R. M. TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and induces apoptosis in pancreatic cancer: involvement of Notch-1 signaling pathway. Cancer Res, 2009, 69(7), 2757-65.
145. Ackler, S.; Xiao, Y.; Mitten, M. J.; Foster, K.; Oleksijew, A.; Refici, M.; Schlessinger, S.; Wang, B.; Chemburkar, S. R.; Bauch, J.; Tse, C.; Frost, D. J.; Fesik, S. W.; Rosenberg, S. H.; Elmore, S. W.; Shoemaker, A. R. ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo. Mol Cancer Ther, 2008, 7(10), 3265-74.
146. Porter, J. R.; Helmers, M. R.; Wang, P.; Furman, J. L.; Joy, S. T.; Arora, P. S.; Ghosh, I. Profiling small molecule inhibitors against helix-receptor interactions: the Bcl-2 family inhibitor BH3I-1 potently inhibits p53/hDM2. Chem Commun (Camb), 2010, 46(42), 8020-2.
147. Day, C. L.; Chen, L.; Richardson, S. J.; Harrison, P. J.; Huang, D. C.; Hinds, M. G. Solution structure of prosurvival Mcl-1 and characterization of its binding by proapoptotic BH3-only ligands. J Biol Chem, 2005, 280(6), 4738-44. (Pubitemid 40288644)
148. Chen, L.; Willis, S. N.; Wei, A.; Smith, B. J.; Fletcher, J. I.; Hinds, M. G.; Colman, P. M.; Day, C. L.; Adams, J. M.; Huang, D. C. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell, 2005, 17(3), 393-403. (Pubitemid 40193310)
149. Tahir, S. K.; Wass, J.; Joseph, M. K.; Devanarayan, V.; Hessler, P.; Zhang, H.; Elmore, S. W.; Kroeger, P. E.; Tse, C.; Rosenberg, S. H.; Anderson, M. G. Identification of expression signatures predictive of sensitivity to the Bcl-2 family member inhibitor ABT-263 in small cell lung carcinoma and leukemia/lymphoma cell lines. Mol Cancer Ther, 2010, 9(3), 545-57.
150. Schwickart, M.; Huang, X.; Lill, J. R.; Liu, J.; Ferrando, R.; French, D. M.; Maecker, H.; O'Rourke, K.; Bazan, F.; Eastham-Anderson, J.; Yue, P.; Dornan, D.; Huang, D. C.; Dixit, V. M. Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature, 2010, 463(7277), 103-7.
151. Parikh, S. A.; Kantarjian, H.; Schimmer, A.; Walsh, W.; Asatiani, E.; El-Shami, K.; Winton, E.; Verstovsek, S. Phase II study of obatoclax mesylate (GX15-070), a small-molecule BCL-2 family antagonist, for patients with myelofibrosis. Clin Lymphoma Myeloma Leuk, 2010, 10(4), 285-9.
152. Raab, R.; Sparano, J. A.; Ocean, A. J.; Christos, P.; Ramirez, M.; Vinciguerra, V.; Kaubisch, A. A phase I trial of oblimersen sodium in combination with cisplatin and 5-fluorouracil in patients with advanced esophageal, gastroesophageal junction, and gastric carcinoma. Am J Clin Oncol, 2010, 33(1), 61-5.
153. Weecharangsan, W.; Yu, B.; Zheng, Y.; Liu, S.; Pang, J. X.; Lee, L. J.; Marcucci, G.; Lee, R. J. Efficient delivery of antisense oligodeoxyribonucleotide g3139 by human serum albumin-coated liposomes. Mol Pharm, 2009, 6(6), 1848-55.
154. Pan, X.; Chen, L.; Liu, S.; Yang, X.; Gao, J. X.; Lee, R. J. Antitumor activity of G3139 lipid nanoparticles (LNPs). Mol Pharm, 2009, 6(1), 211-20.
155. Pro, B.; Leber, B.; Smith, M.; Fayad, L.; Romaguera, J.; Hagemeister, F.; Rodriguez, A.; McLaughlin, P.; Samaniego, F.; Zwiebel, J.; Lopez, A.; Kwak, L.; Younes, A. Phase II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in combination with rituximab in patients with recurrent B-cell non-Hodgkin lymphoma. Br J Haematol, 2008, 143(3), 355-60.
156. Moulder, S. L.; Symmans, W. F.; Booser, D. J.; Madden, T. L.; Lipsanen, C.; Yuan, L.; Brewster, A. M.; Cristofanilli, M.; Hunt, K. K.; Buchholz, T. A.; Zwiebel, J.; Valero, V.; Hortobagyi, G. N.; Esteva, F. J. Phase I/II study of G3139 (Bcl-2 antisense oligonucleotide) in combination with doxorubicin and docetaxel in breast cancer. Clin Cancer Res, 2008, 14(23), 7909-16.
157. Sternberg, C. N.; Dumez, H.; Van Poppel, H.; Skoneczna, I.; Sella, A.; Daugaard, G.; Gil, T.; Graham, J.; Carpentier, P.; Calabro, F.; Collette, L.; Lacombe, D. Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer. Ann Oncol, 2009, 20(7), 1264-9.
158. Shah, M. H.; Varker, K. A.; Collamore, M.; Zwiebel, J. A.; Coit, D.; Kelsen, D.; Chung, K. Y. G3139 (Genasense) in patients with advanced merkel cell carcinoma. Am J Clin Oncol, 2009, 32(2), 174-9.
159. Bedikian, A. Y.; Millward, M.; Pehamberger, H.; Conry, R.; Gore, M.; Trefzer, U.; Pavlick, A. C.; De Conti, R.; Hersh, E. M.; Hersey, P.; Kirkwood, J. M.; Haluska, F. G. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol, 2006, 24(29), 4738-45. (Pubitemid 46630937)
160. Chanan-Khan, A. A.; Niesvizky, R.; Hohl, R. J.; Zimmerman, T. M.; Christiansen, N. P.; Schiller, G. J.; Callander, N.; Lister, J.; Oken, M.; Jagannath, S. Phase III randomised study of dexamethasone with or without oblimersen sodium for patients with advanced multiple myeloma. Leuk Lymphoma, 2009, 50(4), 559-65.
161. O'Brien, S.; Moore, J. O.; Boyd, T. E.; Larratt, L. M.; Skotnicki, A. B.; Koziner, B.; Chanan-Khan, A. A.; Seymour, J. F.; Gribben, J.; Itri, L. M.; Rai, K. R. 5-year survival in patients with relapsed or refractory chronic lymphocytic leukemia in a randomized, phase III trial of fludarabine plus cyclophosphamide with or without oblimersen. J Clin Oncol, 2009, 27(31), 5208-12.
162. Heist, R. S.; Fain, J.; Chinnasami, B.; Khan, W.; Molina, J. R.; Sequist, L. V.; Temel, J. S.; Fidias, P.; Brainerd, V.; Leopold, L.; Lynch, T. J. Phase I/II study of AT-101 with topotecan in relapsed and refractory small cell lung cancer. J Thorac Oncol, 2010, 5(10), 1637-43.
163. Ready, N.; Karaseva, N. A.; Orlov, S. V.; Luft, A. V.; Popovych, O.; Holmlund, J. T.; Wood, B. A.; Leopold, L. Double-blind, placebo-controlled, randomized phase 2 study of the proapoptotic agent AT-101 plus docetaxel, in second-line non-small cell lung cancer. J Thorac Oncol, 2011, 6(4), 781-5.
164. Liu, G.; Kelly, W. K.; Wilding, G.; Leopold, L.; Brill, K.; Somer, B. An open-label, multicenter, phase I/II study of single-agent AT-101 in men with castrate-resistant prostate cancer. Clin Cancer Res, 2009, 15(9), 3172-6.
165. Baggstrom, M. Q.; Qi, Y.; Koczywas, M.; Argiris, A.; Johnson, E. A.; Millward, M. J.; Murphy, S. C.; Erlichman, C.; Rudin, C. M.; Govindan, R. A phase II study of AT-101 (Gossypol) in chemotherapy-sensitive recurrent extensive-stage small cell lung cancer. J Thorac Oncol, 2011, 6(10), 1757-60.
166. Hwang, J. J.; Kuruvilla, J.; Mendelson, D.; Pishvaian, M. J.; Deeken, J. F.; Siu, L. L.; Berger, M. S.; Viallet, J.; Marshall, J. L. Phase I dose finding studies of obatoclax (GX15-070), a small molecule pan-BCL-2 family antagonist, in patients with advanced solid tumors or lymphoma. Clin Cancer Res, 2010, 16(15), 4038-45.
167. O'Brien, S. M.; Claxton, D. F.; Crump, M.; Faderl, S.; Kipps, T.; Keating, M. J.; Viallet, J.; Cheson, B. D. Phase I study of obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist, in patients with advanced chronic lymphocytic leukemia. Blood, 2009, 113(2), 299-305.
168. Wilson, W. H.; O'Connor, O. A.; Czuczman, M. S.; La Casce, A. S.; Gerecitano, J. F.; Leonard, J. P.; Tulpule, A.; Dunleavy, K.; Xiong, H.; Chiu, Y. L.; Cui, Y.; Busman, T.; Elmore, S. W.; Rosenberg, S. H.; Krivoshik, A. P.; Enschede, S. H.; Humerickhouse, R. A. Navitoclax, a targeted highaffinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 doseescalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol, 2010, 11(12), 1149-59.
169. Pond, G. R.; Armstrong, A. J.; Wood, B. A.; Brookes, M.; Leopold, L.; Berry, W. R.; de Wit, R.; Eisenberger, M. A.; Tannock, I. F.; Sonpavde, G. Evaluating the Value of Number of Cycles of Docetaxel and Prednisone in Men With Metastatic Castration-Resistant Prostate Cancer. Eur Urol, 2011.
170. Schimmer, A. D.; O'Brien, S.; Kantarjian, H.; Brandwein, J.; Cheson, B. D.; Minden, M. D.; Yee, K.; Ravandi, F.; Giles, F.; Schuh, A.; Gupta, V.; Andreeff, M.; Koller, C.; Chang, H.; Kamel-Reid, S.; Berger, M.; Viallet, J.; Borthakur, G. A phase I study of the pan bcl-2 family inhibitor obatoclax mesylate in patients with advanced hematologic malignancies. Clin Cancer Res, 2008, 14(24), 8295-301.
171. Paik, P. K.; Rudin, C. M.; Brown, A.; Rizvi, N. A.; Takebe, N.; Travis, W.; James, L.; Ginsberg, M. S.; Juergens, R.; Markus, S.; Tyson, L.; Subzwari, S.; Kris, M. G.; Krug, L. M. A phase I study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in solid tumor malignancies. Cancer Chemother Pharmacol, 2010, 66(6), 1079-85.
172. Paik, P. K.; Rudin, C. M.; Pietanza, M. C.; Brown, A.; Rizvi, N. A.; Takebe, N.; Travis, W.; James, L.; Ginsberg, M. S.; Juergens, R.; Markus, S.; Tyson, L.; Subzwari, S.; Kris, M. G.; Krug, L. M. A phase II study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in relapsed small cell lung cancer. Lung Cancer, 2011.
173. Gandhi, L.; Camidge, D. R.; Ribeiro de Oliveira, M.; Bonomi, P.; Gandara, D.; Khaira, D.; Hann, C. L.; McKeegan, E. M.; Litvinovich, E.; Hemken, P. M.; Dive, C.; Enschede, S. H.; Nolan, C.; Chiu, Y. L.; Busman, T.; Xiong, H.; Krivoshik, A. P.; Humerickhouse, R.; Shapiro, G. I.; Rudin, C. M. Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncol, 2011, 29(7), 909-16.