AMG 232 是一种有效,选择性,可口服的 p53-MDM2 相互作用抑制剂,IC50 值为 0.6 nM,与 MDM2 结合的 Kd 为 0.045 nM。
Description | AMG 232 is a potent, selective and orally available inhibitor of p53-MDM2 interaction, with an IC50 of 0.6 nM. AMG 232 binds to MDM2 with a Kd of 0.045 nM. | ||||||||||||||||
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IC50 & Target | |||||||||||||||||
In Vitro | AMG 232 (10 μM) induces p53 signaling and inhibits tumor cell proliferation in three p53 wild-type tumor cell lines (SJSA-1, HCT116, and ACHN)[1]. AMG 232 significantly inhibits the human MDM2-p53 interaction in the biochemical HTRF-based assay (IC50=0.6 nM). AMG 232 potently inhibits proliferation of non-MDM2-amplified HCT116 colorectal cells in the BrdU assay (IC50=10 nM)[3]. | ||||||||||||||||
In Vivo | AMG 232 (10, 25, 75 mg/kg, p.o.) activates p53 pathway activity in vivo. AMG 232 (100 mg/kg, p.o.) results in 86% TGI compared with control, and the ED50 is 31 mg/kg in the HCT116 colorectal cancer model (KRAS mutant), and results in 97% TGI, with an ED50 of 18 mg/kg in an A375sq2 BRAF-mutant melanoma model[1]. AMG 232 exhibits low clearance (<0.25 × Qh) and moderate to high oral bioavailability in mice, rats and monkeys (>42%), but high clearance (0.74 × Qh) and low oral exposure in dogs (18%)[2]. AMG 232 displays robust tumor growth inhibition compared to the vehicle, with an ED50 of 9.1 mg/kg q.d. AMG 232 causes a dose-dependent tumor growth inhibition with an ED50 of 16 mg/kg[3]. | ||||||||||||||||
Clinical Trial | | ||||||||||||||||
Solvent & Solubility | In Vitro: DMSO : ≥ 50 mg/mL (87.94 mM) H2O : < 0.1 mg/mL (insoluble) * "≥" means soluble, but saturation unknown. Preparing Stock Solutions
* Please refer to the solubility information to select the appropriate solvent. In Vivo:
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References | |
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