AT-406 (SM-406)
AT-406 (SM-406, CAS 1071992-99-8) is an orally bioavailable, small molecule antagonist targeting inhibitor of apoptosis proteins (IAPs). It selectively binds to XIAP, cIAP1, and cIAP2 with Ki values of 66.4 nM, 1.9 nM, and 5.1 nM, respectively. AT-406 treatment induces apoptosis in cancer cells, including human ovarian carcinoma cell lines (IC50: 0.05-0.5 μg/ml), sensitizing them to standard chemotherapy such as carboplatin. In animal cancer models (e.g., ovarian and breast tumors), AT-406 administration reduced tumor progression and enhanced survival. AT-406 is under investigation for its therapeutic potential in oncology research.
References:
Schimmer A D. Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice[J]. Cancer research, 2004, 64(20): 7183-7190.
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]. Journal of medicinal chemistry, 2011, 54(8): 2714-2726.
Zhang T, Li Y. et al. APhysiologically 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.
Hurwitz HI1, Smith DC, et al. Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study. Cancer ChemotherPharmacol. 2015 Apr;75(4):851-9.
- 1. Chao-Yu Yang, Chia-I Lien, et al. "Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis." Nat Commun. 2024 May 6;15(1):3791. PMID: 38710704
- 2. Lars Pache, Matthew D. Marsden, et al. "Pharmacological Activation of Non-canonical NF-κB Signaling Activates Latent HIV-1 Reservoirs In Vivo." Cell Rep Med. 2020 Jun 23;1(3):100037. PMID: 33205060
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 561.71 |
| Cas No. | 1071992-99-8 |
| Formula | C32H43N5O4 |
| Solubility | ≥27.65 mg/mL in DMSO; insoluble in H2O; ≥27 mg/mL in EtOH |
| Chemical Name | (5S,8S,10aR,Z)-N-benzhydryl-5-((Z)-((S)-1-hydroxy-2-(methylamino)propylidene)amino)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carbimidic acid |
| SDF | Download SDF |
| Canonical SMILES | CC(CC(N(C[C@@](/N=C(O)/[C@](NC)([H])C)([H])C1=O)CC[C@@](N21)([H])CC[C@@]2([H])/C(O)=N/C(C3=CC=CC=C3)C4=CC=CC=C4)=O)C |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
MDA-MB-231 breast cancer cell lines |
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Preparation method |
Soluble in DMSO > 27.65mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.1,0.3,1,3μM for 24 hours(analysis of cell death), 1.5μM for 1,3,6,12,24hours(Western blot analysis of caspase processing and cleavage of PARP (poly (ADP-ribose) polymerase)) |
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Applications |
AT-406 was a potent and orally bioavailable antagonist of multiple inhibitor of apoptosis proteins (IAPs). AT-406 effectively antagonized XIAP BIR3 (XIAP: X-linked IAP BIR3: the third BIR domain) protein, induced rapid degradation of cIAP1 (cIAP1: cellular IAP1) protein in MDA-MB-231 cell. AT-406 was effective in inhibition of cell growth in approximately 15% of more than 100 human cancer cell lines and its activity was not limited to a single tumor type. |
| Animal experiment [2]: | |
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Animal models |
SCID(severe combined immunodeficient) mice bearing human MDA-MB-231 xenograft tumor |
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Dosage form |
30 and 100mg/kg(between pH3.0 and 9.0)for oral gavage, 10mg/kg(between pH4.5 and 9.0)for intravenous administration. |
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Application |
AT-406 could lead to the cIAP1 degradation, pro-caspase 8 decrease, CL-PARP(cleaved PARP)accumulation and tumor growth inhibition in the mouse xenograft model. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. 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]. Journal of medicinal chemistry, 2011, 54(8): 2714-2726. [2]. Zhang T, Li Y. et al. APhysiologically 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. |
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Quality Control & MSDS
- View current batch:
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Purity = 98.00%
- COA (Certificate Of Analysis)
- MSDS (Material Safety Data Sheet)
Chemical structure
