A novel small-molecule inhibitor of Mcl-1 blocks pancreatic cancer growth in vitro and in vivo

Molecular Cancer Therapeutics

Volumn 13, Issue 3, 2014, Pages 565-575

  Abulwerdi, Fardokht ^a,b   Liao, Chenzhong ^a   Liu, Meilan ^a   Azmi, Asfar S ^c   Aboukameel, Amro ^c   Mady, Ahmed S A ^a,b   Gulappa, Thippeswamy ^a   Cierpicki, Tomasz ^a   Owens, Scott ^a   Zhang, Tao ^b   Sun, Duxin ^b   Stuckey, Jeanne A ^b   Mohammad, Ramzi M ^c   Nikolovska Coleska, Zaneta ^a,b  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MICHIGAN   (United States)

^c WAYNE STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CYTOCHROME C; PROTEIN BAK; PROTEIN MCL 1; UMI 77; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER GROWTH; CHEMICAL MODIFICATION; CONTROLLED STUDY; FEMALE; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN FUNCTION; XENOGRAFT;

ANIMALS; APOPTOSIS; BCL-2 HOMOLOGOUS ANTAGONIST-KILLER PROTEIN; BCL-2-ASSOCIATED X PROTEIN; CELL LINE, TUMOR; CELL PROLIFERATION; DIMERIZATION; HUMANS; LEAD; MICE; MYELOID CELL LEUKEMIA SEQUENCE 1 PROTEIN; PANCREATIC NEOPLASMS; SULFONAMIDES; THIOGLYCOLATES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84896280569     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-12-0767     Document Type: Article

References (41)

1. Bardeesy N, DePinho RA. Pancreatic cancer biology and genetics. Nat Rev Cancer 2002;2:897-909. (Pubitemid 37328891)
2. Hamacher R, Schmid RM, Saur D, Schneider G. Apoptotic pathways in pancreatic ductal adenocarcinoma. Mol Cancer 2008;7:64.
3. Shi X, Liu S, Kleeff J, Friess H, Buchler MW. Acquired resistance of pancreatic cancer cells towards 5-Fluorouracil and gemcitabine is associated with altered expression of apoptosis-regulating genes. Oncology 2002;62:354-62. (Pubitemid 34914105)
4. Fischer U, Schulze-Osthoff K. Apoptosis-based therapies and drug targets. Cell Death Differ 2005;12 Suppl 1:942-61. (Pubitemid 41030608)
5. Day CL, Chen L, Richardson SJ, Harrison PJ, Huang DC, Hinds MG. Solution structure of prosurvival Mcl-1 and characterization of its binding by proapoptotic BH3-only ligands. J Biol Chem 2005;280: 4738-44. (Pubitemid 40288644)
6. Day CL, Smits C, Fan FC, Lee EF, Fairlie WD, Hinds MG. Structure of the BH3 domains from the p53-inducible BH3-only proteins Noxa and Puma in complex with Mcl-1. J Mol Biol 2008;380: 958-71.
7. Zhou P, Qian L, Kozopas KM, Craig RW. Mcl-1, a Bcl-2 family member, delays the death of hematopoietic cells under a variety of apoptosis-inducing conditions. Blood 1997;89:630-43. (Pubitemid 27051700)
8. Miyamoto Y, Hosotani R, Wada M, Lee JU, Koshiba T, Fujimoto K, et al. Immunohistochemical analysis of Bcl-2, Bax, Bcl-X, and Mcl-1 expression in pancreatic cancers. Oncology 1999;56:73-82. (Pubitemid 29043900)
9. Schniewind B, Christgen M, Kurdow R, Haye S, Kremer B, Kalthoff H, et al. Resistance of pancreatic cancer to gemcitabine treatment is dependent on mitochondria-mediated apoptosis. Int J Cancer 2004;109:182-8. (Pubitemid 38240918)
10. Ren LN, Li QF, Xiao FJ, Yan J, Yang YF, Wang LS, et al. Endocrine glands-derived vascular endothelial growth factor protects pancreatic cancer cells from apoptosis via upregulation of the myeloid cell leukemia-1 protein. Biochem Biophys Res Commun 2009;386:35-9.
11. Wei SH, Dong K, Lin F, Wang X, Li B, Shen JJ, et al. Inducing apoptosis and enhancing chemosensitivity to gemcitabine via RNA interference targeting Mcl-1 gene in pancreatic carcinoma cell. Cancer Chemother Pharmacol 2008;62:1055-64.
12. Guoan X, Hanning W, Kaiyun C, Hao L. Adenovirus-mediated siRNA targeting Mcl-1 gene increases radiosensitivity of pancreatic carcinoma cells in vitro and in vivo. Surgery 2010;147:553-61.
13. Huang S, Sinicrope FA. BH3 mimetic ABT-737 potentiates TRAIL-mediated apoptotic signaling by unsequestering Bim and Bak in human pancreatic cancer cells. Cancer Res 2008;68:2944-51. (Pubitemid 351556295)
14. Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005;435:677-81. (Pubitemid 40825512)
15. Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 2008;68:3421-8.
16. Zhou H, Chen J, Meagher JL, Yang CY, Aguilar A, Liu L, et al. Design of Bcl-2 and Bcl-xL inhibitors with subnanomolar binding affinities based upon a new scaffold. J Med Chem 2012;55:4664-82.
17. van Delft MF, Wei AH, Mason KD, Vandenberg CJ, Chen L, Czabotar PE, et al. 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;10:389-99.
18. Chen S, Dai Y, Harada H, Dent P, Grant S. Mcl-1 down-regulation potentiates ABT-737 lethality by cooperatively inducing Bak activation and Bax translocation. Cancer Res 2007;67:782-91. (Pubitemid 46192219)
19. Nikolovska-Coleska Z, Wang R, Fang X, Pan H, Tomita Y, Li P, et al. Development and optimization of a binding assay for the XIAP BIR3 domain using fluorescence polarization. Anal Biochem 2004;332: 261-73. (Pubitemid 39485734)
20. Czabotar PE, Lee EF, van Delft MF, Day CL, Smith BJ, Huang DC, et al. Structural insights into the degradation of Mcl-1 induced by BH3 domains. Proc Natl Acad Sci U S A 2007;104:6217-22. (Pubitemid 47186075)
21. Schrödinger Suite 2010 Induced Fit Docking protocol. Glide version 5.6, Schrödinger, LLC, 2009; Prime version 2.2. New York, NY: Schrödinger, LLC; 2010.
22. Macromodel 9.8, Schrodinger, LLC, New York, NY. 2010.
23. Banerjee S, Kaseb AO, Wang Z, Kong D, Mohammad M, Padhye S, et al. Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Res 2009;69:5575-83.
24. Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 2007;26:1324-37. (Pubitemid 46328466)
25. Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, et al. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl- 2, until displaced by BH3-only proteins. Genes Dev 2005;19: 1294-305. (Pubitemid 41003019)
26. Bajwa N, Liao C, Nikolovska-Coleska Z. Inhibitors of the antiapoptotic Bcl-2 proteins: a patent review. Expert Opin Ther Pat 2012;22:37-55.
27. Yang CY, Wang S. Analysis of flexibility and hotspots in Bcl-xL and Mcl-1 proteins for the design of selective small-molecule inhibitors. ASC Med Chem Lett 2012;3:308-12.
28. Doi K, Li R, Sung SS, Wu H, Liu Y, Manieri W, et al. Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation. J Biol Chem 2012;287:10224- 35.
29. Lee EF, Czabotar PE, van Delft MF, Michalak EM, Boyle MJ, Willis SN, et al. A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation. J Cell Biol 2008; 180:341-55. (Pubitemid 351185920)
30. Friberg A, Vigil D, Zhao B, Daniels RN, Burke JP, Garcia-Barrantes PM, et al. Discovery of potent myeloid cell leukemia 1 (Mcl-1) inhibitors using fragment-based methods and structure-based design. J Med Chem 2013;56:15-30.
31. Yu J, Zhang L. PUMA, a potent killer with or without p53. Oncogene 2008;27 Suppl 1:S71-83.
32. Villunger A, Michalak EM, Coultas L, Mullauer F, Bock G, Ausserlechner MJ, et al. p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science 2003;302:1036-8. (Pubitemid 37386194)
33. Yuan Z, Cao K, Lin C, Li L, Liu HY, Zhao XY, et al. The p53 upregulated modulator of apoptosis (PUMA) chemosensitizes intrinsically resistant ovarian cancer cells to cisplatin by lowering the threshold set by Bcl-x (L) and Mcl-1. Mol Med 2011;17:1262-74.
34. Willis SN, Fletcher JI, Kaufmann T, van Delft MF, Chen L, Czabotar PE, et al. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 2007;315:856-9.
35. Takahashi Y, Karbowski M, Yamaguchi H, Kazi A,WuJ, Sebti SM, et al. Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis. Mol Cell Biol 2005;25:9369-82. (Pubitemid 41507838)
36. Hanahan D,Weinberg RA. The hallmarks of cancer.Cell 2000;100:57-70. (Pubitemid 30046295)
37. Hinds MG, Day CL. Regulation of apoptosis: uncovering the binding determinants. Curr Opin Struct Biol 2005;15:690-9. (Pubitemid 41668526)
38. Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, et al. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell 2005;17: 393-403. (Pubitemid 40193310)
39. Griffiths GJ, Dubrez L, Morgan CP, Jones NA, Whitehouse J, Corfe BM, et al. Cell damage-induced conformational changes of the proapoptotic protein Bak in vivo precede the onset of apoptosis. J Cell Biol 1999;144:903-14. (Pubitemid 29238967)
40. Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ, Schlesinger PH. Proapoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ 2000;7:1166-73. (Pubitemid 32042223)
41. Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 2001;292:727-30. (Pubitemid 32385543)