DeBio-1143 (AT-406)
DeBio-1143, also known as AT-406, ARRY-334543and SM-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.
1: Hurwitz HI, Smith DC, Pitot HC, Brill JM, Chugh R, Rouits E, Rubin J, Strickler J, Vuagniaux G, Sorensen JM, Zanna C. Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study. Cancer Chemother Pharmacol. 2015 Apr;75(4):851-9. doi: 10.1007/s00280-015-2709-8. Epub 2015 Feb 27. PubMed PMID: 25716544; PubMed Central PMCID: PMC4365270.
2: Lu J, Qin Q, Zhan LL, Liu J, Zhu HC, Yang X, Zhang C, Xu LP, Liu ZM, Wang D, Cui HQ, Meng CC, Cai J, Cheng HY, Sun XC. AT-406, an IAP inhibitor, activates apoptosis and induces radiosensitization of normoxic and hypoxic cervical cancer cells. J Pharmacol Sci. 2014;126(1):56-65. Epub 2014 Aug 27. PubMed PMID: 25168470.
3: Zhang T, Li Y, Zou P, Yu JY, McEachern D, Wang S, Sun D. Physiologically based pharmacokinetic and pharmacodynamic modeling of an antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in a mouse xenograft model of human breast cancer. Biopharm Drug Dispos. 2013 Sep;34(6):348-59. doi: 10.1002/bdd.1850. Epub 2013 Aug 2. PubMed PMID: 23813446.
4: Brunckhorst MK, Lerner D, Wang S, Yu Q. AT-406, an orally active antagonist of multiple inhibitor of apoptosis proteins, inhibits progression of human ovarian cancer. Cancer Biol Ther. 2012 Jul;13(9):804-11. Epub 2012 Jun 6. PubMed PMID: 22669575; PubMed Central PMCID: PMC3679100.
5: 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. doi: 10.1021/jm101505d. Epub 2011 Mar 28. PubMed PMID: 21443232; PubMed Central PMCID: PMC3520070.
6: Björn LO. Photoinactivation of catalases from mammal liver, plant leaves and bacteria. Comparison of inactivation cross sections and quantum yields at 406 nm. Photochem Photobiol. 1969 Aug;10(2):125-9. PubMed PMID: 5803017.
2: Lu J, Qin Q, Zhan LL, Liu J, Zhu HC, Yang X, Zhang C, Xu LP, Liu ZM, Wang D, Cui HQ, Meng CC, Cai J, Cheng HY, Sun XC. AT-406, an IAP inhibitor, activates apoptosis and induces radiosensitization of normoxic and hypoxic cervical cancer cells. J Pharmacol Sci. 2014;126(1):56-65. Epub 2014 Aug 27. PubMed PMID: 25168470.
3: Zhang T, Li Y, Zou P, Yu JY, McEachern D, Wang S, Sun D. Physiologically based pharmacokinetic and pharmacodynamic modeling of an antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in a mouse xenograft model of human breast cancer. Biopharm Drug Dispos. 2013 Sep;34(6):348-59. doi: 10.1002/bdd.1850. Epub 2013 Aug 2. PubMed PMID: 23813446.
4: Brunckhorst MK, Lerner D, Wang S, Yu Q. AT-406, an orally active antagonist of multiple inhibitor of apoptosis proteins, inhibits progression of human ovarian cancer. Cancer Biol Ther. 2012 Jul;13(9):804-11. Epub 2012 Jun 6. PubMed PMID: 22669575; PubMed Central PMCID: PMC3679100.
5: 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. doi: 10.1021/jm101505d. Epub 2011 Mar 28. PubMed PMID: 21443232; PubMed Central PMCID: PMC3520070.
6: Björn LO. Photoinactivation of catalases from mammal liver, plant leaves and bacteria. Comparison of inactivation cross sections and quantum yields at 406 nm. Photochem Photobiol. 1969 Aug;10(2):125-9. PubMed PMID: 5803017.
| Chemical | |
|---|---|
| CAS Num | 1071992-99-8 |
| Chemical Formula | C32H43N5O4 |
| Molecular Weight | 561.727 |
| IUPAC Chemical Name | (5S,8S,10aR)-N-benzhydryl-5-((S)-2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide |
| Exact Mass | 561.3315 |
| Elemental Analysis | C, 68.42; H, 7.72; N, 12.47; O, 11.39 |
| Synonym | DeBio-1143; DeBio1143; DeBio 1143; AT-406; AT406; AT 406; SM 406; SM406; ARRY-334543; ARRY334543; ARRY 334543. |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | O=C([C@@H]1CC[C@@](CCN(C(CC(C)C)=O)C[C@@H]2NC([C@@H](NC)C)=O)([H])N1C2=O)NC(C3=CC=CC=C3)C4=CC=CC=C4 |
| Biological | |
| Targets and Effects | Apoptosis Protein inhibitor |
| Pathways | Apoptosis |
| Physical | |
| Appearance | White to off-white solid powder |
| Purity | >98% (or refer to the Certificate of Analysis) |
| Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
| Storage Condition | Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Shelf Life | >2 years if stored properly |
Mailing Address
Anba Pharma Company
3-H Gill Street, Suite 300
Woburn, MA 01801
United State
Our Contact Info.
Tel: 1+610-883-0668
Email: sales@AnbaPharma.com