| Identification | Back Directory | [Name]
AMG 232 | [CAS]
1352066-68-2 | [Synonyms]
AMG 232
CS-1300
AMG-232; AMG 232
2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-[(2S)-3-methyl-1-propan-2-ylsulfonylbutan-2-yl]-2-oxopiperidin-3-yl]acetic acid(AMG232)
3-Piperidineacetic acid, 5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-[(1S)-2-methyl-1-[[(1-methylethyl)sulfonyl]methyl]propyl]-2-oxo-, (3R,5R,6S)- | [Molecular Formula]
C28H35Cl2NO5S | [MOL File]
1352066-68-2.mol | [Molecular Weight]
568.55 |
| Chemical Properties | Back Directory | [Melting point ]
160-164oC | [Boiling point ]
732.7±60.0 °C(Predicted) | [density ]
1.254±0.06 g/cm3(Predicted) | [storage temp. ]
-20°C Freezer | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
4.29±0.10(Predicted) | [color ]
White to Off-White |
| Hazard Information | Back Directory | [Uses]
AMG-232 is a potent MDM2-P53 inhibitor for use as an anti-tumor agent. | [Biological Activity]
amg-232 is a novel inhibitor of p53-mdm2 with ic50 value of 9.2 nm [1].tumor protein p53 (p53) is a very unstable protein with a half-life ranging from 5 to 30 min and participates in a variety of anticancer processes, such as inducing cell apoptosis and inhibiting angiogenesis. mouse double minute 2 homolog (mdm2), also named as e3 ubiquitin-protein ligase mdm2, involves in mediating p53 tumor suppressor. it has been conclusively demonstrated p53 is under-expressed in tumor cells [2].amg-232 is a potent p53-mdm2 interaction inhibitor and is regarded as a promising drug in clinic. when tested with sjsa-1 tumor cell line, amg-232 treatment resulted in cell-cycle arrest and inhibition of tumor cell proliferation via binding to mdm2 protein and robustly inducing p53 activity. it was shown that p53-mdm2 bond rang from a kd of 60 to 700 nm depending on the length of p53 peptide [3].in mouse model with sjsa-1 tumor cells subcutaneous xenograft, co-administration of amg-232 and chemotherapies induced dna damage and p53 activity which resulted in significantly superior antitumor efficacy and regression through arresting cell growth and inducting apoptosis [3]. | [in vivo]
Navtemadlin (AMG 232) (10, 25, 75 mg/kg, once daily, p.o.) activates p53 pathway activity in vivo[1].
Navtemadlin (10, 25, 75 mg/kg, once daily, p.o.) potently inhibits growth of tumor xenografts in mice[1].
Navtemadlin (10, 25, 75 mg/kg, once daily, p.o.) blocks DNA synthesis and induces apoptosis in vivo[1].
Navtemadlin causes a dose-dependent tumor growth inhibition with an ED50 of 16 mg/kg[2]. | Animal Model: | Female athymic nude mice (n=10/group) based cancer models[1]. | | Dosage: | 10, 25, 75 mg/kg. | | Administration: | Once daily by oral gavage. | | Result: | Resulted in significant tumor growth inhibition across all models. SJSA-1, an MDM2 amplified osteosarcoma model, was the most sensitive to AMG 232 treatment with an ED50 of 9.1 mg/kg. In the highest dose group of 75 mg/kg, 10/10 tumors completely regressed and were undetectable after 10 days of treatment. |
| [target]
MDM2?p53 interaction | [storage]
Store at -20°C,unstable in solution, ready to use. | [References]
[1]. rew, y., et al., discovery of am-7209, a potent and selective 4-amidobenzoic acid inhibitor of the mdm2-p53 interaction. j med chem, 2014. 57(24): p. 10499-511.
[2]. moll, u.m. and o. petrenko, the mdm2-p53 interaction. mol cancer res, 2003. 1(14): p. 1001-8.
[3]. canon, j., et al., the mdm2 inhibitor amg 232 demonstrates robust antitumor efficacy and potentiates the activity of p53-inducing cytotoxic agents. mol cancer ther, 2015. 14(3): p. 649-58. |
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BOC Sciences
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1-631-485-4226; 16314854226 |
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https://www.bocsci.com |
| Company Name: |
SPIRO PHARMA
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| Tel: |
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| Website: |
www.spiropharma.com.cn |
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