Navtemadlin (AMG232) is a potent, selective and orally available inhibitor of p53-MDM2 interaction (IC50: 0.6 nM). It binds to MDM2 with a Kd of 0.045 nM.

MDM2:0.045 nM (Kd), p53-MDM2:0.6 nM

METHODS: Navtemadlin (0.1, 1, 10 μM) treated B16-F10 cells to determine whether reactivation of p53 by Navtemadlin would induce tumor growth arrest.
RESULTS Navtemadlin induced significant p53-dependent growth arrest but minimal apoptosis in B16-F10 cells. [1]

METHODS: Navtemadlin (AMG232)(20 mg/kg (ip)) was used to treat C57Bl/6 mice bearing B16-F10 melanoma tumors to observe whether it inhibited tumor growth in mice.
RESULTS When Navtemadlin (AMG232) was administered daily starting from day 3, p53 tumor size was reduced by approximately 30%-50%. [1]
METHODS: Navtemadlin (AMG232) (10, 25, 75 mg/kg, once daily, orally) was used to observe whether it could inhibit the growth of mouse tumor xenografts.
RESULTS Navtemadlin (AMG232) activated p53 pathway activity in vivo and effectively inhibited the growth of mouse tumor xenografts. It also blocked DNA synthesis and induced apoptosis in vivo[2].

Cell 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 [1]. Incubation Time: 72 hours.

Animal Model: Female athymic nude mice (n=10) based cancer models. Dosage: 10, 25, 75 mg/kg. Administration: Once daily by oral gavage [1].