Serdemetan (JNJ-26854165)

MDM2

328, 41

CB17SC scid-/- female mice.

JNJ 26854165 is currently being evaluated in Phase I clinical trials in patients with Neoplasms.

<=20 mg/kg

JNJ 26854165 is a novel tryptamine derivative which activates p53 and acts as a HDM2 ubiquitin ligase antagonist. JNJ 26854165 inhibits cell growth and induces apoptosis in leukemia cell lines with IC50 values of 0.24, 0.33, 0.32 and 0.44 uM at 72 hours for OCI-AML-3, MOLM-13, NALM-6 and REH cells, respectively. In addition, JNJ 26854165 accelerates, proteasome-mediated degradation of p21 and antagonizes the transcriptional induction of p21 by p53. It also induces S-phase delay and upregulates E2F1 expression in p53 mutant cells, resulting in preferential apoptosis, of S-phase cells. [1] JNJ 26854165 is an oral Mdm2 inhibitor which can inhibit the interaction of Mdm2-p53 complex with the proteasome and increase p53 levels by binding to RING domain of Mdm2. [2] A recent study shows that JNJ 26854165 inhibits clonogenic survival in four human cancer cell lines: H460, A549, p53-WT-HCT116, and p53-null-HCT116. [3]

72 hours

DMSO 66 mg/mL, Water <1 mg/mL, Ethanol 2 mg/mL

N1-(2-(1H-indol-3-yl)ethyl)-N4-(pyridin-4-yl)benzene-1, 4-diamine