[CAS NO. 1071992-57-8] Xevinapanthydrochloride
PRODUCTS SPECIFICATIONS [1071992-57-8]
DESCRIPTION [1071992-57-8]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 598.18 |
| Molecular Formula | C32H44ClN5O4 |
| 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.[H]Cl |
3 Publications Citing Use of MCE
Summary
Xevinapant (AT-406) hydrochloride is a potent and orally bioavailable Smac mimetic and an antagonist of the inhibitor of apoptosis proteins (IAPs) . Xevinapant hydrochloride binds to XIAP , cIAP1 , and cIAP2 proteins with K i s of 66.4, 1.9, and 5.1 nM, respectively. Xevinapant hydrochloride effectively antagonizes XIAP BIR3 protein in a cell-free functional assay, induces rapid degradation of cellular cIAP1 protein, and inhibits cancer cell growth in various human cancer cell lines. Xevinapant hydrochloride is highly effective in induction of apoptosis in xenograft tumors [1] [2] .
IC50 & Target
|
cIAP1 1.9 nM (Ki) |
cIAP2 5.1 nM (Ki) |
XIAP 66.4 nM (Ki) |
In Vitro
Xevinapant (AT-406) hydrochloride potently inhibits cell growth in the MDA-MB-231 breast and SK-OV-3 ovarian cancer cell lines with IC 50 =144 nM and 142 nM, respectively. Xevinapant (0-3 μM; 0-48 horus) hydrochloride effectively induces cell death in a time- and dose-dependent manner [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Xevinapant (AT-406) hydrochloride is very effective in inhibition of tumor growth in the MDA-MB-231 xenograft model, and has minimal toxicity to animals
[1]
.
Xevinapant hydrochloride evaluated for its pharmacokinetic (PK) properties in mice, rats, non-human primates and dogs
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | SCID mice bearing MDA-MB-231 xenograft tumors [1] |
| Dosage: | 30 and 100 mg/kg |
| Administration: | p.o.; 5 days a week for 2 weeks |
| Result: | Strongly inhibits tumor growth at 30 and 100 mg/kg and completely inhibits tumor growth during the treatment with 100 mg/kg. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT01930292 | Debiopharm International SA |
Solid Tumors
|
April 2013 | Phase 1 |
| NCT03871959 | Centre Leon Berard|Merck Sharp & Dohme LLC|Debiopharm International SA |
Adenocarcinoma of the Pancreas|Adenocarcinoma of the Colon|Adenocarcinoma of the Rectum
|
September 15, 2019 | Phase 1 |
| NCT02022098 | Debiopharm International SA |
Squamous Cell Carcinoma of the Head and Neck
|
October 2013 | Not Applicable |
| NCT03270176 | Debiopharm International SA |
Carcinoma, Non-Small-Cell Lung|Neoplasms
|
October 10, 2017 | Phase 1 |
| NCT01265199 | Ascenta Therapeutics|The Leukemia and Lymphoma Society |
Acute Myelogenous Leukemia (AML)
|
February 2011 | Phase 1 |
| NCT05519540 | Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany|Merck KGaA, Darmstadt, Germany |
Healthy
|
September 26, 2022 | Phase 1 |
| NCT04459715 | EMD Serono Research & Development Institute, Inc.|GORTEC (Head and Neck Oncology and Radiotherapy Group)|Merck KGaA, Darmstadt, Germany|EMD Serono |
Squamous Cell Carcinoma of the Head and Neck
|
August 7, 2020 | Phase 3 |
| NCT04122625 | Debiopharm International SA |
Solid Tumor
|
April 8, 2019 | Phase 1|Phase 2 |
| NCT01078649 | Debiopharm International SA |
Cancer|Solid Tumors|Lymphoma|Malignancy
|
March 29, 2010 | Phase 1 |
| NCT04962724 | Debiopharm International SA |
Healthy Volunteers
|
August 2, 2021 | Phase 1 |
| NCT05386550 | EMD Serono Research & Development Institute, Inc.|Merck KGaA, Darmstadt, Germany|EMD Serono |
Head and Neck Cancer
|
October 6, 2022 | Phase 3 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Solvent & Solubility
DMSO : 175 mg/mL ( 292.55 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.6717 mL | 8.3587 mL | 16.7174 mL |
| 5 mM | 0.3343 mL | 1.6717 mL | 3.3435 mL |
| 10 mM | 0.1672 mL | 0.8359 mL | 1.6717 mL |
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 Med Chem. 2011;54(8):2714-2726.
- [2] Brunckhorst MK, et al. AT-406, an orally active antagonist of multiple inhibitor of apoptosis proteins, inhibits progression of human ovarian cancer. Cancer Biol Ther. 2012;13(9):804-811.