1. Apoptosis
  2. IAP
  3. Xevinapant

Xevinapant (Synonyms: AT-406; Debio 1143; SM-406)

Cat. No.: HY-15454 Purity: 98.80%
Handling Instructions

Xevinapant (AT-406) is a potent and orally bioavailable Smac mimetic and an antagonist of IAPs, and it binds to XIAP, cIAP1, and cIAP2 proteins with Ki of 66.4, 1.9, and 5.1 nM, respectively.

For research use only. We do not sell to patients.

Xevinapant Chemical Structure

Xevinapant Chemical Structure

CAS No. : 1071992-99-8

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 161 In-stock
Estimated Time of Arrival: December 31
5 mg USD 130 In-stock
Estimated Time of Arrival: December 31
10 mg USD 200 In-stock
Estimated Time of Arrival: December 31
25 mg USD 400 In-stock
Estimated Time of Arrival: December 31
50 mg USD 620 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Based on 2 publication(s) in Google Scholar

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Description

Xevinapant (AT-406) is a potent and orally bioavailable Smac mimetic and an antagonist of IAPs, and it binds to XIAP, cIAP1, and cIAP2 proteins with Ki of 66.4, 1.9, and 5.1 nM, respectively.

IC50 & Target

Ki: 66.4 nM (XIAP), 1.9 nM (cIAP1), 5.1 nM (cIAP2)

In Vitro

Xevinapant mimic closely the AVPI peptide in both hydrogen bonding and hydrophobic interactions with XIAP, with additional hydrophobic contacts with W323 of XIAP. Xevinapant is more sensitive to these IAPs than Smac AVPI peptide with 50-100 fold binding affinities. Xevinapant (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, Xevinapant induces rapid cellular cIAP1 degradation and also pulls down the cellular XIAP protein. Xevinapant 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. Xevinapant induces apoptosis in MDA-MB-231 cell by inducing activation of caspase-3 and cleavage of PARP[1]. Xevinapant displays single agent activity in ovarian cancer cell lines. The IC50 values of AT-406 in these ovarian cancer cells range from 0.05-0.5 µg/mL. Xevinapant exhibits anti-ovarian cancer efficacy both as a single agent and in combination with carboplatin. Xevinapant (30 μg/mL) induced degradation of XIAP in the drug sensitive ovarian cancer cell lines[2].

In Vivo

Xevinapant has good pharmacokinetic properties and oral bioavailability in mice, rats, non-human primates, and dogs. In the MDA-MB-231 xenograft, Xevinapant 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. Xevinapant induces significant tumor growth inhibition with p of 0.0012 at 100 mg/kg[2]. Xevinapant (30, 100 mg/kg, p.o.) decreases the plasma and tumor in tumor-bearing mice[3].

Clinical Trial
Molecular Weight

561.71

Formula

C₃₂H₄₃N₅O₄

CAS No.

1071992-99-8

SMILES

O=C([[email protected]@H]1CC[[email protected]@](CCN(C(CC(C)C)=O)C[[email protected]@H]2NC([[email protected]@H](NC)C)=O)([H])N1C2=O)NC(C3=CC=CC=C3)C4=CC=CC=C4

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : ≥ 100 mg/mL (178.03 mM)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 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
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (4.45 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.5 mg/mL (4.45 mM); Clear solution

  • 3.

    Add each solvent one by one:  10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (4.45 mM); Clear solution

*All of the co-solvents are provided by MCE.
References
Cell Assay
[1]

Cells are seeded in 96-well flat bottom cell culture plates at a density of 3-4×103 cells/well with Xevinapant and incubated for 4 days. The rate of cell growth inhibition after treatment with different concentrations of Xevinapant is determined by assaying with WST-8. WST-8 is added to each well to a final concentration of 10%, and then the plates are incubated at 37°C for 2-3 hours. The absorbance of the samples is measured at 450 nm using a TECAN ULTRA reader. Concentration of AT-406 that inhibits cell growth by 50% (IC50) is calculated by comparing absorbance in the untreated cells and the cells treated with Xevinapant.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

SCID mice (8-10 per group) bearing MDA-MB-231 xenograft tumors are treated with different doses of compound 2, or 7.5 mg/kg of Taxotere or vehicle control daily, 5 days a week for 2 weeks. Tumor sizes and animal weights are measured 3 times a week during the treatment and twice a week after the treatment. Data are presented as mean tumor volumes±SEM. Statistical analyses are performed by two-way ANOVA and unpaired two-tailed t test, using Prism. P < 0.05 is considered statistically significant.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
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Keywords:

XevinapantAT-406Debio 1143SM-406AT406AT 406Debio1143Debio-1143SM406SM 406IAPInhibitorinhibitorinhibit

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