MedKoo product information:

 AT-406

Description of AT-406 : AT-406  is an orally bioavailable inhibitor of IAP (Inhibitor of Apoptosis Protein) family of proteins with potential apoptotic inducing and antineoplastic activity. AT-406 selectively inhibits the biological activity of IAP proteins, including X chromosome-linked IAP (XIAP), the cellular IAPs 1 (c-IAP1) and 2 (c-IAP2) and melanoma inhibitor of apoptosis protein (ML-IAP). This may restore and promote the induction of apoptosis through apoptotic signaling pathways. AT-406 may work synergistically with cytotoxic drugs to overcome tumor cell resistance to apoptosis. IAPs are overexpressed by many cancer cell types, suppressing apoptosis by binding and inhibiting active caspases-3, -7 and -9 via their BIR (baculoviral lAP repeat) domains. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:   Ascenta Therapeutics, Inc.

AT-406, currently being developed by   Ascenta Therapeutics, has demonstrated strong single-agent antitumor activity in multiple xenograft models of human cancer, including breast cancer, pancreatic cancer, prostate cancer, and lung cancer. AT-406 has also been shown to work synergistically with conventional chemotherapeutic and targeted agents (such as TRAIL and tyrosine kinase inhibitors) in preclinical tumor models. (source: http://www.ascenta.com/development/index.php).

Preclinical evaluation of AT-406: According to news release by Ascenta Therapeutics, The preclinical research of AT-406 has demonstrated that AT-406 showed strong single-agent antitumor activity in multiple xenograft models of human cancer, including breast cancer, pancreatic cancer, prostate cancer, and lung cancer. AT-406 has also been shown to work synergistically with conventional chemotherapeutic and targeted agents (such as tyrosine kinase inhibitors) in preclinical tumor models.

1. Cai Q, Sun H, Peng Y, Lu J, Nikolovska-Coleska Z, McEachern D, Liu L, Qiu S, Yang CY, 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 Apr 28;54(8):2714-26.

2. Targeting cancer stem cells By Buchsbaum, Donald J.; LoBuglio, Albert F.; Zhou, Tong From PCT Int. Appl. (2011), WO 2011116344 A2 20110922.

3. Potent Bivalent Smac Mimetics: Effect of the Linker on Binding to Inhibitor of Apoptosis Proteins (IAPs) and Anticancer Activity By Sun, Haiying; Liu, Liu; Lu, Jianfeng; Bai, Longchuan; Li, Xiaoqin; Nikolovska-Coleska, Zaneta; McEachern, Donna; Yang, Chao-Yie; Qiu, Su; Yi, Han; et al From Journal of Medicinal Chemistry (2011), 54(9), 3306-3318.

4. Preparation of diazo bicyclic conformationally constrained Smac peptide mimetics as inhibitors of IAP proteins and inducers of apoptosis By Wang, Shaomeng; Peng, Yuefeng; Sun, Haiying; Cai, Qian; Nikolovska-Coleska, Zaneta; Lu, Jianfeng; Qiu, Su From PCT Int. Appl. (2008), WO 2008128171 A2 20081023.