AMG 232

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AMG 232 是一种有效的、选择性的、口服生物可利用的 MDM2-p53 抑制剂，Kd 为 0.045 nM。

AMG 232 is a potent, selective, orally bioavailable MDM2-p53 inhibitor with Kd of 0.045 nM, inhibits SJSA-1 cell proliferation with IC50 of 9.1 nM; robustly induces p53 activity, leading to cell-cycle arrest and inhibition of tumor cell proliferation; significantly inhibits tumor growth in SJSA-1 osteosarcoma xenograft model with ED50 of 9.1 mg/kg, also showsignificantly superior antitumor efficacy chombined with chemotherapies in vivo, enhances radiosensitivity via inhibition of damage repair signaling.Skin Cancer Phase 2 Clinical.

Navtemadlin (AMG 232) (10 μM) induces p53 signaling and inhibits tumor cell proliferation in three p53 wild-type tumor cell lines. Navtemadlin potently inhibits proliferation of non-MDM2-amplified HCT116 colorectal cells (IC50=10 nM).Cell Viability AssayCell Line:SJSA-1, HCT116, ACHN, NCI-H460, MOLM-13, RKO, MCF7, 22RV1, HT-29, PC-3, NCI-H82, NCI-SNU1, MG-63, NCI-H2452, SW982, C32, SK-HEP-1, A375, RT4, RPMI2650, MDA-MB-134-VI, NCI-H2347 and A427 cells.Concentration:0-10 μM.Incubation Time:72 hours.Result:Induced p53 signaling and inhibits tumor cell proliferation in three p53 wild-type tumor cell lines (SJSA-1, HCT116, and ACHN).Caused robust p21 mRNA induction between 9.76 and 34.9 fold with IC50 values ranging from 12.8 to 46.8 nM.

Navtemadlin (AMG 232) (10, 25, 75 mg/kg, once daily, p.o.) activates p53 pathway activity in vivo.Navtemadlin (10, 25, 75 mg/kg, once daily, p.o.) potently inhibits growth of tumor xenografts in mice.Navtemadlin (10, 25, 75 mg/kg, once daily, p.o.) blocks DNA synthesis and induces apoptosis in vivo.Navtemadlin causes a dose-dependent tumor growth inhibition with an ED50 of 16 mg/kg. Animal Model:Female athymic nude mice (n=10/group) based cancer models.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.

AMG232 | AMG-232

Apoptosis

MDM2-p53

MDM2-p53

Cancer

Skin Cancer

1352066-68-2

568.5522

C28H35Cl2NO5S

>98% (HPLC)

10 mM in DMSO

CC(C)S(C[C@H](C(C)C)N(C1=O)[C@@H]([C@H](C[C@@]1(CC(O)=O)C)C2=CC=CC(Cl)=C2)C3=CC=C(C=C3)Cl)(=O)=O

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)-

(-20℃)

With Ice Pack

≥ 2 years