Small molecule inhibitor of apoptosis proteins antagonists: a patent review

Bibliography

• Kerr JFR, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics. Br J Cancer 1972;26:239-57
   PubMed Web of Science ®Google Scholar
• Carson DA, Ribiero JM. Apoptosis and disease. Lancet 1993;341:1251-4
   PubMed Web of Science ®Google Scholar
• Solary E, Dubrez L, Eymin B. The role of apoptosis in the pathogenesis and treatment of disease. Eur Respir J 1996;9:1293-305
   Google Scholar
• Salvesen GS, Duckett CS. IAP proteins: blocking the road to death’s door. Nat Rev Mol Cell Biol 2002;3:401-10
   PubMed Web of Science ®Google Scholar
• Gyrd-Hansen M, Meier P. IAPs: From caspase inhibitors to modulators of NF-κB, inflammation, and cancer. Nat Rev Cancer 2010;10:561-74
   PubMed Web of Science ®Google Scholar
• Dubrez L, Berthelet J, Glorian V. IAP proteins as targets for drug development in oncology. Onco Targets Ther 2013;6:1285-304
   Web of Science ®Google Scholar
• Holcik M, Gibson H, Korneluk RG. XIAP: apoptotic brake and promising therapeutic target. Apoptosis 2001;6:253-61
   PubMed Web of Science ®Google Scholar
• Tamm I, Kornblau SM, Segall H, et al. Expression and prognostic significance of IAPfamily genes in human cancers and myeloid leukemias. Clin Cancer Res 2000;6:1796-803
   PubMed Web of Science ®Google Scholar
• Yang L, Cao Z, Yan H, Wood WC. Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: Implication for cancer specific therapy. Cancer Res 2003;63:6815-24
   PubMed Web of Science ®Google Scholar
• Vucic D, Fairbrother WJ. The inhibitor of apoptosis proteins as therapeutic targets in cancer. Clin Cancer Res 2007;13:5995-6000
   PubMed Web of Science ®Google Scholar
• Chai J, Du C, Wu JW, et al. Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature 2000;406:855-62
   PubMed Web of Science ®Google Scholar
• Liu Z, Sun C, Olejniczak ET, et al. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature 2000;408:1004-8
   PubMed Web of Science ®Google Scholar
• Wu G, Chai J, Suber TL, et al. Structural basis of IAP recognition by Smac/DIABLO. Nature 2000;408:1008-12
   PubMed Web of Science ®Google Scholar
• Sharma SK, Straub C, Zawel L. Development of peptidomimetics targeting IAPs. Int J Pept Res Ther 2006;12:21-32
   PubMed Web of Science ®Google Scholar
• Bai L, Smith DC, Wang S. Small-molecule Smac mimetics as new cancer therapeutics. Pharmacol Ther 2014;144:82-95
   PubMed Web of Science ®Google Scholar
• Cossu F, Milani M, Mastrangelo E, et al. Structural basis for bivalent Smac-mimetics recognition in the IAP protein family. J Mol Biol 2009;392:630-44
   Google Scholar
• Sun H, Nikolovska-Coleska Z, Lu J, et al. 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;129:15279-94
   PubMed Web of Science ®Google Scholar
• Cossu F, Milani M, Vachette P, et al. Structural insight into inhibitor of apoptosis proteins recognition by a potent divalent smac-mimetic. PLoS One 2012;7:e49527
   Google Scholar
• Wu H, Tschopp J, Lin SC. Smac mimetics and TNFalpha: a dangerous liaison? Cell 2007;131:655-8
   PubMed Web of Science ®Google Scholar
• Ndubaku C, Varfolomeev E, Wang L, et al. Antagonism of c-IAP and XIAP proteins is required for efficient induction of cell death by small-molecule IAP antagonists. ACS Chem Biol 2009;4:557-66
   Google Scholar
• Varfolomeev E, Blankenship JW, Wayson SM, et al. IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell 2007;131:669-81
   PubMed Web of Science ®Google Scholar
• Erickson RI, Tarrant J, Cain G, et al. Toxicity profile of small-molecule IAP antagonist GDC-0152 is linked to TNF-alpha pharmacology. Toxicol Sci 2013;131:247-58
   Google Scholar
• Obexer P, Ausserlechner MJ. X-linked inhibitor of apoptosis protein – a critical death resistance regulator and therapeutic target for personalized cancer therapy. Front Oncol 2014;4:197
   PubMedGoogle Scholar
• Ardecky RJ, Welsh K, Finlay D, et al. Design, synthesis and evaluation of inhibitor of apoptosis protein (IAP) antagonists that are highly selective for the BIR2 domain of XIAP. Bioorg Med Chem Lett 2013;23:4253-7
   Google Scholar
• Kester RF, Donnell AF, Lou Y, et al. Optimization of benzodiazepinones as selective inhibitors of the X-linked inhibitor of apoptosis protein (XIAP) second baculovirus IAP repeat (BIR2) domain. J Med Chem 2013;56:7788-803
   Google Scholar
• Donnell AF, Michoud C, Rupert KC, et al. Benzazepinones and Benzoxazepinones as Antagonists of Inhibitor of Apoptosis Proteins (IAPs) Selective for the Second Baculovirus IAP Repeat (BIR2) Domain. J Med Chem 2013;56:7772-87
   Google Scholar
• Du C, Fang M, Li Y, et al. Smac, a mitochondrial protein that promotes cytochrome c dependent caspase activation by eliminating IAP inhibition. Cell 2000;102:33-42
   PubMed Web of Science ®Google Scholar
• Verhagen AM, Ekert PG, Pakusch M, et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 2000;102:43-53
   PubMed Web of Science ®Google Scholar
• Results were obtained by a search in SciFinder™, Available from: http://scifinder.cas.org, for the terms “IAP”, “inhibitors of apoptosis protein” and “smac”. Searches for unrelated topics were then removed from the results (“IAPP” (islet amyloid polypeptide), “inhibitor affinity purification”, “amyloid”, (index of) “atmospheric purity”, (institute of) “atmospheric physics”. SciFinder is a registered trademark of the American Chemical Society
   Google Scholar
• Condon SM. The discovery and development of Smac mimetics-small-molecule antagonists of the inhibitor of apoptosis proteins Annu Rep Med Chem. 2011;46:211-26
   Google Scholar
• Jaquith JB. Targeting the inhibitor of apoptosis protein BIR3 binding domains. Pharm Pat Anal 2014;3:297-312
   Google Scholar
• Flygare JA, Fairbrother WJ. Small-molecule pan-IAP antagonists: a patent review. Expert Opin Ther Pat 2010;20:251-67
   Web of Science ®Google Scholar
• SciFinder is a registered trademark of the American Chemical Society. Available from: http://scifinder.cas.org
   Google Scholar
• Note: additional searches of “livin” or “survivin” only yielded one patent application between 2010-2014 that exemplified small molecule inhibitors of survivin dimerization. See; The Trustees of the University of Pennsylvania. Method of treating cancer using a survivin inhibitor. WO083505; 2010
   Google Scholar
• Aegera Therapeutics, Inc. IAP BIR domain binding compounds. WO098904; 2011
   Google Scholar
• Pukac L, Kanakaraj P, Humphreys R, et al. HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death in multiple tumor types in vitro and in vivo. Br J Cancer 2005;25:1430-41
   Google Scholar
• Chessari G, Maria A, Buck I, et al. AT-IAP, a dual cIAP1 and XIAP antagonist with oral antitumor activity in melanoma model. Cancer Res 2013;73(8 Suppl):2944
   Google Scholar
• Astex Therapeutics. Bicyclic heterocycle compounds and their uses in therapy. WO060767; 2014
   Google Scholar
• Astex Therapeutics. Bicyclic heterocycle compounds and their uses in therapy. WO060768; 2014
   Google Scholar
• Astex Therapeutics. Bicyclic heterocycle compounds and their uses in therapy. WO060770; 2014
   Google Scholar
• Avila Therapeutics. Ligand-directed covalent modification of protein. WO082285; 2011
   Google Scholar
• Boehringer Ingelheim International GmbH. 5-alkynyl pyridine. US0225567; 2013
   Google Scholar
• Genentech, Inc. Inhibitors of IAP. US0172264; 2013
   Google Scholar
• Genentech, Inc. Inhibitors of IAP. WO017035; 2010
   Google Scholar
• Genentech, Inc. Azaindole inhibitors of IAP. WO021934; 2010
   Google Scholar
• Jin H, Yang R, Ross J, et al. Cooperation of the agonistic DR5 antibody apomab with chemotherapy to inhibit orthotopic lung tumor growth and improve survival. Clin Cancer Res 2008;14:7733-40
   PubMed Web of Science ®Google Scholar
• Hanmi Holdings Co. Imidazopyrazinone derivatives with apoptosis inducing activity on cells. WO090317; 2011
   Google Scholar
• Hoffman-La Roche. Substituted hetero-azepinones. WO023708; 2014
   Google Scholar
• Hoffman-La Roche. Azaheterocycles as BIR2 and/or BIR3 inhibitors. WO026882; 2014
   Google Scholar
• Hoffman-La Roche. Azaindolines. WO056871; 2014
   Google Scholar
• Sanford-Burnham Medical Research Institute. Inhibitor of apoptosis protein (IAP) antagonists. WO085489; 2014
   Google Scholar
• Takeda Pharmaceutical Co. Ltd. Alanine derivatives as inhibitors of apoptosis proteins. WO016576; 2011
   Google Scholar
• Takeda Pharmaceutical Co. Ltd. Heterocyclic compounds, pharmaceuticals containing them, method for antagonizing inhibitors of apoptosis proteins by the compounds, and prevention or treatment of cancer using them. JP106958; 2012
   Google Scholar
• Takeda Pharmaceutical Co. Ltd. Heterocyclic compounds as IAP (inhibitors of apoptosis protein) antagonists and pharmaceuticals containing them. JP176934; 2012
   Google Scholar
• Tetralogic Pharmaceuticals Corp. IAP inhibitors. WO033531; 2010
   Google Scholar
• Tetralogic Pharmaceuticals Corp. IAP inhibitors. WO138496; 2010
   Google Scholar
• Tetralogic Pharmaceuticals Corp. IAP inhibitors. WO138666; 2010
   Google Scholar
• Tetralogic Pharmaceuticals Corp. IAP inhibitors. WO068926; 2011
   Google Scholar
• Aegera Therapeutics, Inc. IAP BIR domain binding compounds. WO031171; 2010
   Google Scholar
• Aegera Therapeutics, Inc. IAP BIR domain binding compounds. US0141496; 2012
   Google Scholar
• Aegera Therapeutics, Inc. Functionalized pyrrolidines and use thereof as IAP inhibitors. WO015090; 2010
   Google Scholar
• Bristol-Myers Squibb Co. and Ensemble Therapeutics Corp. Macrocyclic compounds for inhibition of inhibitors of apoptosis. WO074658; 2014
   Google Scholar
• Bristol-Myers Squibb Co. and Ensemble Therapeutics Corp. Macrocyclic compounds for inhibition of inhibitors of apoptosis. WO074665; 2014
   Google Scholar
• Bristol-Myers Squibb Co. IAP antagonists. US0338081; 2013
   Google Scholar
• Bristol-Myers Squibb Co. IAP antagonists. WO055461; 2014
   Google Scholar
• Bristol-Myers Squibb Co. IAP antagonists. WO047024; 2014
   Google Scholar
• Bristol-Myers Squibb Co. IAP antagonists. WO011712; 2014
   Google Scholar
• Bristol-Myers Squibb Co. IAP antagonists. WO025759; 2014
   Google Scholar
• AstraZeneca AB. 2,3-Dihydro-1H-indene compounds and their use to treat cancer. WO142994; 2010
   Google Scholar
• Hennessy EJ, Adam A, Aquila BM, et al. Discovery of a Novel Class of Dimeric Smac Mimetics as Potent IAP Antagonists Resulting in a Clinical Candidate for the Treatment of Cancer (AZD5582). J Med Chem 2013;56:9897-919
   Google Scholar
• Joyant Pharmaceuticals. Dimeric Smac mimetics. WO059763; 2011
   Google Scholar
• Chen KF, Lin JP, Shiau CW, et al. Inhibition of Bcl-2 improves effect of LCL161, a SMAC mimetic, in hepatocellular carcinoma cells. Biochem Pharmacol 2012;84:268-77
   Web of Science ®Google Scholar
• Novartis AG. Dimeric IAP inhibitors. WO080271; 2012
   Google Scholar
• Novartis AG. Dimeric IAP inhibitors. WO080260; 2012
   Google Scholar
• Novartis AG. Dimeric IAP inhibitors. WO104266; 2011
   Google Scholar
• Hoffman-La Roche. Dimeric compounds. WO090709; 2014
   Google Scholar
• The regents of the University of Michigan. Bivalent diazo bicyclic Smac mimetics and the uses thereof. WO050068; 2011
   Google Scholar
• The regents of the University of Michigan. Bivalent inhibitors of IAP proteins and therapeutic methods using the same. WO031487; 2014
   Google Scholar
• Cai Q, Sun H, Peng Y, et al. 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;54:2714-26
   PubMed Web of Science ®Google Scholar
• Hanmi Holdings Co. Quinoline or quinazoline derivatives with apoptosis inducing activity on cells. WO030160; 2012
   Google Scholar
• Hennequin LF, Stokes Elaine SE, Thomas A, et al. Novel 4-Anilinoquinazolines with C-7 Basic Side Chains: Design and Structure Activity Relationship of a Series of Potent, Orally Active, VEGF Receptor Tyrosine Kinase Inhibitors. J Med Chem 2002;45:1300-12
   PubMed Web of Science ®Google Scholar
• Bean J, Riely GJ, Balak M, et al. Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novelT854A mutation in a patient with EGFRMutant lung adenocarcinoma. Clin Cancer Res 2008;14:7519-25
   PubMed Web of Science ®Google Scholar
• Barker AJ, Gibson KH, Grundy W, et al. Studies leading to the identification of ZD1839 (iressa): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer. Bioorg Med Chem Lett 2001;11:1911-14
   PubMed Web of Science ®Google Scholar
• Rusnak DW, Lackey K, Affleck K, et al. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther 2001;1:85-94
   PubMed Web of Science ®Google Scholar
• The Rockefeller University. Mitochondrial targeted stimulators of apopotosis. US0244325; 2013
   Google Scholar
• Pieczykolan JS, Kubiński K, Maslyk M, et al. AD-O53.2 – a novel recombinant fusion protein combining the activities of TRAIL/Apo2L and Smac/Diablo, overcomes resistance of human cancer cells to TRAIL/Apo2L Invest. New Drugs 2014;32:1155-66
   Google Scholar
• During the preparation of this manuscript, additional data for Debio 1143 has appeared Tourneau CL, Ray-coquard I, Isambert N, et al. Debio 1143 in combination with carboplatin and paclitaxel in patients with non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC) and platinum-refractory epithelial ovarian cancer (EOC) [abstract number 444]. Preliminary results of a Phase I dose-escalation study. Presented at the 26th Annual EORTC-NCI-AACR Meeting; 18 – 21 November 2014; Barcelona, Spain. Poster Available from https://www.debiopharm.com/images/stories/files/publications/2014-Debio_1143_in_combination_with_carboplatin.pdf
   Google Scholar
• Wong H, Gould SE, Budha N, et al. Learning and confirming with preclinical studies: modeling and simulation in the discovery of GDC-0917, an inhibitor of apoptosis proteins antagonist. Drug Metab Dispos 2013;41:2104-13
   PubMed Web of Science ®Google Scholar
• Allensworth JL, Sauer SJ, Lyerly HK, et al. Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-α-independent mechanism. Breast Cancer Res Treat 2013;137:359-71
   Google Scholar
• During the preparation of this manuscript, additional data for Birinapant has appeared in two abstracts Borthakur G, Foran JM, Wang E, et al. A Phase 1b/2a Study of Birinapant in Combination with 5-Azacitadine in Patients with Myelodysplastic Syndrome Who Are Naïve, Refractory to or Have Relapsed on 5-Azacitadine: a Preliminary Analysis [abstract 3263]. Presented at the 56th Annual American Society of Hematology Annual Meeting and Exposition; 6 – 9 December 2014; San Francisco, California. Available from: https://ash.confex.com/ash/2014/webprogram/Paper68257.html
   Google Scholar
• Frey N, Luger S, Mangan J, et al. A Phase I Study Using Single Agent Birinapant in Patients with Relapsed Myelodysplastic Syndrome and Acute Myelogenous Leukemia [abstract 3758]. Presented at the 56th Annual American Society of Hematology Annual Meeting and Exposition; 6 – 9 December 2014; San Francisco, California. Available from: https://ash.confex.com/ash/2014/webprogram/Paper75637.html
   Google Scholar
• Information around the status of clinical trial information was obtained from a search performed in September 2014 using the following tool: Trialtrove®, 2014. Citeline, an Informa UK business
   Google Scholar
• Sikic B, Eckhardt S, Gallant G, et al. Safety, pharmacokinetics (PK), and pharmacodynamics (PD) of HGS1029, an inhibitor of apoptosis protein (IAP) inhibitor, in patients (Pts) with advanced solid tumors: Results of a phase I study. J Clin Oncol 2012;29(Suppl):3008
   Google Scholar
• Hurwitz H, Pitot H, Smith D, et al. First-in-human, pharmacokinetic (PK), and pharmacodynamics (PD) phase I study of Debio1143 (AT-406) in patients with advanced cancer: final results. J Clin Oncol 2014;32(5s Suppl):abstract 2532
   Google Scholar
• Wong H, Gould S, Budha N, et al. Learning and confirming with preclinical studies: modeling and simulation in the discovery of GDC-0917, an inhibitor of apoptosis proteins antagonist. Drug Metab Dispos 2013;41:2104-13
   PubMed Web of Science ®Google Scholar
• Tolcher A, Papadopoulos K, Patnaik A, et al. Phase I study of safety and pharmacokinetics (PK) of GDC-0917, an antagonist of inhibitor of apoptosis (IAP) proteins in patients (Pts) with refractory solid tumors or lymphoma. J Clin Oncol 2013;31(Suppl):abstract 2503
   Google Scholar
• Infante J, Dees E, Olszanski A, et al. Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. J Clin Oncol 2014;32:3103-10
   PubMed Web of Science ®Google Scholar
• Dienstmann R, Adamo B, Vidal L, et al. Phase Ib study of LCL161, an oral antagonist of inhibitor of apoptosis proteins, in combination with weekly paclitaxel in patients with advanced solid tumors: Safety and efficacy results, including breast cancer cohort [abstract number: PD5-7]. Presented at the 36th Annual San Antonio Breast Cancer Symposium; 10 – 14 December 2013; San Antonio, TX. Available from: http://www.abstracts2view.com/sabcs13/view.php?nu=SABCS13L_1038
   Google Scholar
• Amaravadi R, Schilder R, Dy G, et al. Phase 1 study of the Smac mimetic TL32711 in adult subjects with advanced solid tumors and lymphoma to evaluate safety, pharmacokinetics, pharmacodynamics and antitumor activity [abstract LB-406]. Available from Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2 – 6 Apr 2011; Orlando, Florida
   Google Scholar
• Senzer N, LoRusso P, Martin L, et al. Phase II clinical activity and tolerability of the Smac-mimetic birinapant (TL32711) plus irinotecan in irinotecan-relapsed/refractory metastatic colorectal cancer. J Clin Oncol 2013;31(Suppl):abstract 3621
   Google Scholar
• MOE is the Molecular Operating Environment from the Chemical Computing Group. Available from: www.chemcomp.com
   Google Scholar