Discovery of a novel class of dimeric smac mimetics as potent IAP antagonists resulting in a clinical candidate for the treatment of cancer (AZD5582)

Journal of Medicinal Chemistry

Volumn 56, Issue 24, 2013, Pages 9897-9919

  Hennessy, Edward J ^a   Adam, Ammar ^a   Aquila, Brian M ^a   Castriotta, Lillian M ^a   Cook, Donald ^a   Hattersley, Maureen ^a   Hird, Alexander W ^a   Huntington, Christopher ^a   Kamhi, Victor M ^a   Laing, Naomi M ^a   Li, Danyang ^a   MacIntyre, Terry ^a   Omer, Charles A ^a   Oza, Vibha ^a   Patterson, Troy ^a   Repik, Galina ^a   Rooney, Michael T ^a   Saeh, Jamal C ^a   Sha, Li ^a   Vasbinder, Melissa M ^a   Wang, Haiyun ^a   Whitston, David ^a   more..

^a ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; AZD 5582; CASPASE 3; INHIBITOR OF APOPTOSIS PROTEIN; INHIBITOR OF APOPTOSIS PROTEIN 1; INHIBITOR OF APOPTOSIS PROTEIN 2; UNCLASSIFIED DRUG; X LINKED INHIBITOR OF APOPTOSIS;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; AREA UNDER THE CURVE; ARTICLE; BREAST CANCER; CANCER CELL; CANCER THERAPY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DIMERIZATION; DISTRIBUTION VOLUME; DRUG BLOOD LEVEL; DRUG CLASSIFICATION; DRUG CLEARANCE; DRUG IDENTIFICATION; DRUG POTENCY; DRUG STRUCTURE; HALF LIFE TIME; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PROTEIN DEGRADATION; STEADY STATE; TUMOR REGRESSION; TUMOR XENOGRAFT;

EID: 84891297614     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm401075x     Document Type: Article

References (57)

1. Kerr, J. F. R.; Wyllie, A. H.; Currie, A. R. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics Br. J. Cancer 1972, 26, 239-257
2. Carson, D. A.; Ribiero, J. M. Apoptosis and disease Lancet 1993, 341, 1251-1254
3. Solary, E.; Dubrez, L.; Eymin, B. The role of apoptosis in the pathogenesis and treatment of disease Eur. Respir. J. 1996, 9, 1293-1305
4. Hanahan, D.; Weinberg, R. A. Hallmarks of cancer: The next generation Cell 2011, 144, 646-674
5. Salvesen, G. S.; Duckett, C. S. IAP proteins: Blocking the road to death's door Nat. Rev. Mol. Cell Biol. 2002, 3, 401-410
6. Gyrd-Hansen, M.; Meier, P. IAPs: From caspase inhibitors to modulators of NF-κB, inflammation, and cancer Nat. Rev. Cancer 2010, 10, 561-574
7. Shiozaki, E. N.; Chai, J.; Rigotti, D. J.; Riedl, S. J.; Li, P.; Srinivasula, S. M.; Alnemri, E. S.; Fairman, R.; Shi, Y. Mechanism of XIAP-mediated inhibition of caspase-9 Mol. Cell 2003, 11, 519-527
8. Chai, J.; Shiozaki, E.; Srinivasula, S. M.; Wu, Q.; Dataa, P.; Alnemri, E. S.; Shi, Y. Structural basis of caspase-7 inhibition by XIAP Cell 2001, 104, 769-780
9. Huang, Y.; Park, Y. C.; Rich, R. L.; Segal, D.; Myszka, D. G.; Wu, H. Structural basis of caspase inhibition by XIAP: Differential roles of the linker versus the BIR domain Cell 2001, 104, 781-790
10. Riedl, S. J.; Renatus, M.; Schwarzenbacher, R.; Zhou, Q.; Sun, C.; Fesik, S. W.; Liddington, R. C.; Salvesen, G. S. Structural basis for the inhibition of caspase-3 by XIAP Cell 2001, 104, 791-800
11. Vaux, D. L.; Silke, J. IAPs, RINGs, and ubiquitylation Nat. Rev. Mol. Cell Biol. 2005, 6, 287-297
12. Varfolomeev, E.; Blankenship, J. W.; Wayson, S. M.; Federova, A. V.; Kayagaki, N.; Garg, P.; Zobel, K.; Dynek, J. N.; Elliott, L. O.; Wallweber, H. J. A.; Flygare, J. A.; Fairbrother, W. J.; Deshayes, K.; Dixit, V. M.; Vucic, D. IAP antagonists induce autoubiquitination of c-IAPs, NF-κB activation, and TNFα-dependent apoptosis Cell 2007, 131, 669-681
13. Vince, J. E.; Wong, W. W.-L.; Khan, N.; Feltham, R.; Chau, D.; Ahmed, A. U.; Benetatos, C. A.; Chunduru, S. K.; Condon, S. M.; McKinlay, M.; Brink, R.; Leverkus, M.; Tergaonkar, V.; Schneider, P.; Callus, B. A.; Koentgen, F.; Vaux, D. L.; Silke, J. IAP antagonists target cIAP1 to induce TNFα-dependent apoptosis Cell 2007, 131, 682-693
14. Fotin-Mleczek, M.; Henkler, F.; Samel, D.; Reichwein, M.; Hausser, A.; Parmryd, I.; Scheurich, P.; Schmid, J. A.; Wajant, H. Apoptotic crosstalk of TNF receptors: TNF-R2-induces depletion of TRAF2 and IAP proteins and accelerates TNF-R1-dependent activation of caspase-8 J. Cell Sci. 2002, 115, 2757-2770
15. Tamm, I.; Kornblau, S. M.; Segall, H.; Krajewski, S.; Welsh, K.; Kitada, S.; Scudiero, D. A.; Tudor, G.; Qui, Y. H.; Monks, A.; Andreeff, M.; Reed, J. C. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias Clin. Cancer Res. 2000, 6, 1796-1803
16. Yang, L.; Cao, Z.; Yan, H.; Wood, W. C. Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: Implication for cancer specific therapy Cancer Res. 2003, 63, 6815-6824
17. Vucic, D.; Fairbrother, W. J. The inhibitor of apoptosis proteins as therapeutic targets in cancer Clin. Cancer Res. 2007, 13, 5995-6000
18. Liu, Z.; Sun, C.; Olejniczak, E. T.; Meadows, R. P.; Betz, S. F.; Oost, T.; Herrmann, J.; Wu, J. C.; Fesik, S. W. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain Nature 2000, 408, 1004-1008
19. Wu, G.; Chai, J.; Suber, T. L.; Wu, J.-W.; Du, C.; Wang, X.; Shi, Y. Structural basis of IAP recognition by Smac/DIABLO Nature 2000, 408, 1008-1012
20. Sharma, S. K.; Straub, C.; Zawel, L. Development of peptidomimetics targeting IAPs Int. J. Pept. Res. Ther. 2006, 12, 21-32
21. Sun, H.; Nikolovska-Coleska, Z.; Yang, C.-Y.; Qian, D.; Lu, J.; Qiu, S.; Bai, L.; Peng, Y.; Cai, Q.; Wang, S. Design of small-molecule peptidic and nonpeptidic Smac mimetics Acc. Chem. Res. 2008, 41, 1264-1277
22. Mannhold, R.; Fulda, S.; Carosati, E. IAP antagonists: Promising candidates for cancer therapy Drug Discovery Today 2010, 15, 210-219
23. Flygare, J. A.; Fairbrother, W. J. Small-molecule pan-IAP antagonists: A patent review Expert Opin. Ther. Patents 2010, 20, 251-267
24. Condon, S. M. The discovery and development of Smac-mimetics-small- molecule antagonists of the inhibitor of apoptosis proteins Annu. Rep. Med. Chem. 2011, 46, 211-226
25. Fulda, S.; Vucic, D. Targeting IAP proteins for therapeutic intervention in cancer Nat. Rev. Drug Discovery 2012, 11, 109-124
26. Chai, J.; Du, C.; Wu, J.-W.; Kyin, S.; Wang, X.; Shi, Y. Structural and biochemical basis of apoptotic activation by Smac/DIABLO Nature 2000, 406, 855-862
27. Li, L.; Thomas, R. M.; Suzuki, H.; De Brabander, J. K.; Wang, X.; Harran, P. G. A small molecule Smac mimic potentiates TRAIL- and TNFα-mediated cell death Science 2004, 305, 1471-1474
28. Sun, H.; Nikolovska-Coleska, Z.; Lu, J.; Meagher, J. L.; Yang, C.-Y.; Qiu, S.; Tomita, Y.; Ueda, Y.; Jiang, S.; Krajewski, K.; Roller, P. P.; Stuckey, J. A.; Wang, S. Design, synthesis, and characterization of a potent, nonpeptide, cell-permeable, bivalent Smac mimetic that concurrently targets both the BIR2 and BIR3 domains in XIAP J. Am. Chem. Soc. 2007, 129, 15279-15294
29. Cossu, F.; Milani, M.; Mastrangelo, E.; Vachette, P.; Servida, F.; Lecis, D.; Canevari, G.; Delia, D.; Drago, C.; Rizzo, V.; Manzoni, L.; Seneci, P.; Scolastico, C.; Bolognesi, M. Structural basis for bivalent Smac-mimetics recognition in the IAP protein family J. Mol. Biol. 2009, 392, 630-644
30. Oost, T. K.; Sun, C.; Armstrong, R. C.; Al-Assaad, A.-S.; Betz, S. F.; Deckwerth, T. L.; Ding, H.; Elmore, S. W.; Meadows, R. P.; Olejniczak, E. T.; Oleksijew, A.; Oltersdorf, T.; Rosenberg, S. H.; Shoemaker, A. R.; Tomaselli, K. J.; Zou, H.; Fesik, S. W. Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer J. Med. Chem. 2004, 47, 4417-4426
31. Laurent, A. IAP BIR domain binding compounds. Patent US20070093428, 2007.
32. Petersen, S. L.; Wang, L.; Yalcin-Chin, A.; Li, L.; Peyton, M.; Minna, J.; Harran, P.; Wang, X. Autocrine TNFα signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis Cancer Cell 2007, 12, 445-456
33. Ndubaku, C.; Varfolomeev, E.; Wang, L.; Zobel, K.; Lau, K.; Elliott, L. O.; Maurer, B.; Federova, A. V.; Dynek, J. N.; Kohler, M.; Hymowitz, S. G.; Tsui, V.; Deshayes, K.; Fairbrother, W. J.; Flygare, J. A.; Vucic, D. Antagonism of c-IAP and XIAP proteins is required for efficient induction of cell death by small-molecule IAP antagonists ACS Chem. Biol. 2009, 4, 557-566
34. Hennessy, E. J.; Saeh, J. C.; Sha, L.; MacIntyre, T.; Wang, H.; Larsen, N. A.; Aquila, B. M.; Ferguson, A. D.; Laing, N. M.; Omer, C. A. Discovery of aminopiperidine-based Smac mimetics as IAP antagonists Bioorg. Med. Chem. Lett. 2012, 22, 1690-1694
35. Sun, H.; Liu, L.; Lu, J.; Bai, L.; Li, X.; Nikolovska-Coleska, Z.; McEachern, D.; Yang, C.-Y.; Qiu, S.; Yi, H.; Sun, D.; Wang, S. Potent bivalent Smac mimetics: Effect of the linker on binding to inhibitor of apoptosis proteins (IAPs) and anticancer activity J. Med. Chem. 2011, 54, 3306-3318
36. Feltham, R.; Bettjeman, B.; Budhidarmo, R.; Mace, P. D.; Shirley, S.; Condon, S. M.; Chunduru, S. K.; McKinlay, M. A.; Vaux, D. L.; Silke, J.; Day, C. L. Smac mimetics activate the E3 ligase activity of cIAP1 protein by promoting RING domain dimerization J. Biol. Chem. 2011, 286, 17015-17028
37. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings Adv. Drug Delivery Rev. 2001, 46, 3-26
38. Kipp, R. A.; Case, M. A.; Wist, A. D.; Cresson, C. M.; Carrell, M.; Griner, E.; Wiita, A.; Albiniak, P. A.; Chai, J.; Shi, Y.; Semmelhack, M. F.; McLendon, G. L. Molecular targeting of inhibitor of apoptosis proteins based on small molecule mimics of natural binding partners Biochemistry 2002, 41, 7344-7349
39. Condon, S. M.; LaPorte, M. G.; Deng, Y.; Rippin, S. R. Dimeric IAP inhibitors. Patent WO2006091972, 2006.
40. Nikolovska-Coleska, Z.; Meagher, J. L.; Jiang, S.; Yang, C.-Y.; Qiu, S.; Roller, P. P.; Stuckey, J. A.; Wang, S. Interaction of a cyclic, bivalent Smac mimetic with the X-linked inhibitor of apoptosis protein Biochemistry 2008, 47, 9811-9824
41. Burton, P. S.; Conradi, R. A.; Hilgers, A. R. Transcellular mechanism of peptide and protein absorption: Passive aspects Adv. Drug Delivery Rev. 1991, 7, 365-386
42. Stenberg, P.; Luthman, K.; Artursson, P. Prediction of membrane permeability to peptides from calculated dynamic molecular surface dynamics Pharm. Res. 1999, 16, 205-212
43. Huang, Y.; Rich, R. L.; Myszka, D. G.; Wu, H. Requirement of both the second and third BIR domains for the relief of X-linked inhibitor of apoptosis protein (XIAP)-mediated caspase inhibition by Smac J. Biol. Chem. 2003, 278, 49517-49522
44. Copeland, R. A.; Pompliano, D. L.; Meek, T. D. Drug-target residence time and its implications for lead optimization Nat. Rev. Drug Discovery 2006, 5, 730-739
45. Cai, Q.; Sun, H.; Peng, Y.; Lu, J.; Nikolovska-Coleska, Z.; McEachern, D.; Liu, L.; Qiu, S.; Yang, C.-Y.; Miller, R.; Yi, H.; Zhang, T.; Sun, D.; Kang, S.; Guo, M.; Leopold, L.; Yang, D.; Wang, S. A potent and orally active antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in clinical development for cancer treatment J. Med. Chem. 2011, 54, 2714-2726
46. Petersen, S. L.; Peyton, M.; Minna, J. D.; Wang, X. Overcoming cancer cell resistance to Smac mimetic induced apoptosis by modulating cIAP-2 expression Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 11936-11941
47. Darding, M.; Feltham, R.; Tenev, T.; Bianchi, K.; Benetatos, C.; Silke, J.; Meier, P. Molecular determinants of Smac mimetic induced degradation of cIAP1 and cIAP2 Cell Death Differ. 2011, 18, 1376-1386
48. Bai, L.; McEachern, D.; Yang, C.-Y.; Lu, J.; Sun, H.; Wang, S. LRIG1 modulates cancer cell sensitivity to Smac mimetics by regulating TNFα expression and receptor tyrosine kinase signaling Cancer Res. 2012, 72, 1229-1238
49. Bellucci, C. M.; Bergamini, A.; Cozzi, P. G.; Papa, A.; Tagliavini, E.; Umani-Ronchi, A. Catalytic asymmetric synthesis of secondary alcohols using chiral cis -1-amino-2-hydroxy-1,2,3,4-tetrahydronapthalene as chiral ligand Tetrahedron: Asymmetry 1997, 8, 895-902
50. Winstein, S.; Boschan, R. The role of neighboring groups in replacement reactions. XVII. Complex neighboring groups. The benzamido group J. Am. Chem. Soc. 1950, 72, 4669-4677
51. Higashijima, S.; Itoh, H.; Senda, Y.; Nakano, S. cis -1-Amino-1,2,3,4- tetrahydro-2-napthalenol: Resolution and application to the catalytic enantioselective reduction of ketones Tetrahedron: Asymmetry 1997, 8, 3107-3110
52. Lakshman, M. K.; Chaturvedi, S.; Zajc, B.; Gibson, D. T.; Resnick, S. M. A general chemoenzymatic synthesis of enantiopure cis β-amino alcohols from microbially derived cis-glycols Synthesis 1998, 30, 1352-1356
53. Orsini, F.; Sello, G.; Bestetti, G. Enantiopure vic-amino alcohols and vic-diamines from (1 R,2 S)-1,2-dihydroxy-1,2-dihydronapthalene Tetrahedron: Asymmetry 2001, 12, 2961-2969
54. Shieh, W.-C.; Chen, Z.; Xue, S.; McKenna, J.; Wang, R.-M.; Prasad, K.; Repic, O. Synthesis of sterically-hindered peptidomimetics using 4-(4,6-dimethoxy-1,3,5-triazine-2-yl)-4-methyl-morpolinium chloride Tetrahedron Lett. 2008, 49, 5359-5362
55. Vu, T. C.; Brzozowksi, D. B.; Fox, R.; Godfrey, J. D.; Hanson, R. L.; Kolotuchin, S. V.; Mazzullo, J. A.; Patel, R. N.; Wang, J.; Wong, K.; Yu, J.; Zhu, J.; Magnin, D. R.; Augeri, D. J.; Hamann, L. G. Methods and compounds producing dipeptidyl peptidase IV inhibitors and intermediates thereof. Patent WO2004052850, 2004.
56. Nötzel, M. W.; Labahn, T.; Es-Sayed, M.; de Meijere, A. A new and efficient access to thiazoline-4-carboxylates and cysteine derivatives incorporating cyclopropyl groups Eur. J. Org. Chem. 2001, 3025-3030
57. Walker, B. J.; Wrobel, P. J. Stereospecific cis radical addition. Convincing evidence for a 1,3-radical transfer reaction J. Chem. Soc., Chem. Commun. 1980, 462-463