[CAS NO. 1071992-99-8] Xevinapant (AT406)
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PRODUCTS SPECIFICATIONS [1071992-99-8]
Catelog
SLK-S2754
Brand
Selleck
CAS
1071992-99-8
DESCRIPTION [1071992-99-8]
Overview
| MDL | MFCD22124467 |
|---|---|
| Molecular Weight | 561.71 |
| Molecular Formula | C32H43N5O4 |
| SMILES | 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 |
For research use only.
Storage
3 years,-20°C,powder
1 years,-80°C,in solvent
1 years,-80°C,in solvent
Shipping
Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)
Preparing Stock Solutions
| 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7803 mL | 8.9014 mL | 17.8028 mL |
| 5 mM | 0.3561 mL | 1.7803 mL | 3.5606 mL |
| 10 mM | 0.1780 mL | 0.8901 mL | 1.7803 mL |
| 50 mM | 0.0356 mL | 0.1780 mL | 0.3561 mL |
Description
Xevinapant (AT406, ARRY-334543, Debio1143, SM-406) is a potent Smac mimetic and an antagonist of (inhibitor of apoptosis protein via E3 ubiquitin ligase), binding to XIAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with of 66.4 nM, 1.9 nM, and 5.1 nM, 50- to 100-fold higher affinities than the Smac AVPI peptide. Phase 1.
Targets
In vitro
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.
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