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Activity Type | Activity Value -log(M) | Mechanism of Action | Activity Reference | Publications (PubMed IDs) |
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SKU | Size | Availability | Price | Qty |
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X409188-1ml | 1ml | Available within 4-8 weeks(?) Items will be manufactured post-order and can take 4-8 weeks. Thank you for your patience! | $451.90 |
XIAP Selective Inhibitors | Antagonists
Specifications & Purity | Moligand™, 10mM in DMSO |
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Biochemical and Physiological Mechanisms | Xevinapant (AT406, ARRY-334543, Debio1143, SM-406) is a potent Smac mimetic and an antagonist of IAP (inhibitor of apoptosis protein via E3 ubiquitin ligase), binding to XIAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 66.4 nM, 1.9 nM, and 5.1 n |
Storage Temp | Store at -80°C |
Shipped In | Ice chest + Ice pads |
Grade | Moligand™ |
Action Type | ANTAGONIST |
Mechanism of action | Antagonist of baculoviral IAP repeat containing 2;Antagonist of baculoviral IAP repeat containing 3;Antagonist of X-linked inhibitor of apoptosis |
Product Description | Information Xevinapant (AT406, ARRY-334543, Debio1143, SM-406) is a potent Smac mimetic and an antagonist ofIAP(inhibitor of apoptosis protein via E3 ubiquitin ligase), binding to XIAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 withKiof 66.4 nM, 1.9 nM, and 5.1 nM, 50- to 100-f AT-406 is a Smac mimetic and appears to mimic closely the AVPI peptide in both hydrogen bonding and hydrophobic interactions with XIAP, with additional hydrophobic contacts with W323 of XIAP. AT-406 is more sensitive to these IAPs than Smac AVPI peptide with 50-100 fold binding affinities. AT-406 (at 1 μM) completely restores the activity of caspase-9, which is suppressed by 500 nM XIAP BIR3 in a cell-free system. In MDA-MB-231 cell, AT-406 induces rapid cellular cIAP1 degradation and also pulls down the cellular XIAP protein. AT-406 effectively inhibits lots of human cancer cell lines and shows IC50 of 144 and 142 nM in MDA-MB-231 cell and SK-OV-3 ovarian cell, with low toxicity against normal-like human breast epithelial MCF-12F cells and primary human normal prostate epithelial cells. AT-406 induces apoptosis in MDA-MB-231 cell by inducing activation of caspase-3 and cleavage of PARP. In vivo AT-406 has good pharmacokinetic (PK) properties and oral bioavailability in mice, rats, non-human primates, and dogs. In the MDA-MB-231 xenograft, AT-406 effectively induces cIAP1 degradation and processing of procaspase-8, cleavage of PARP in tumor tissues at 100 mg/kg with well toleration even at 200 mg/kg. AT-406 induces significant tumor growth inhibition with p of 0.0012 at 100 mg/kg. cell lines:SW620, LoVo, V3-YAC and V3 cells Concentrations:~ 1 μM Incubation Time:4 days Powder Purity:≥99% |
Ki Data | XIAP-BIR3, Ki: 66.4 nM |
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Activity Type | Activity Value -log(M) | Mechanism of Action | Activity Reference | Publications (PubMed IDs) |
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Activity Type | Activity Value -log(M) | Mechanism of Action | Activity Reference | Publications (PubMed IDs) |
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Canonical SMILES | CNC(C)C(=O)NC1CN(CCC2CCC(N2C1=O)C(=O)NC(C3=CC=CC=C3)C4=CC=CC=C4)C(=O)CC(C)C |
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Molecular Weight | 561.71 |
Solubility | Solubility (25°C) In vitro DMSO: 64 mg/mL (200.08 mM); Ethanol: 64 mg/mL (200.08 mM); Water: Insoluble; |
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