CAY10682

Description: (±)-Nutlin-3 blocks the interaction of p53 with its negative regulator Mdm2 (IC50 = 90 nM), inducing the expression of p53-regulated genes and blocking the growth of tumor xenografts in vivo. CAY10682 is a pyrrolo[3,4c]pyrazole derivative that inhibits the p53-Mdm2 interaction as potently as (±)-nutlin-3 (Ki = 83 nM) and also dose-dependently reduces activation of the NF-kappaB pathway. It specifically prevents phosphorylation of IkappaBalpha by the kinases IKKalpha, IKKbeta, and IKK (IC50s = 80.5, 78.2, and 57.1 µM, respectively). CAY10682 blocks the growth of cancer cells in vitro (IC50s = 2-6 µM) and inhibits the growth of A549 cell xenografts in mice without significantly reducing body weight. Target: Others. Smiles: C(CCN1C=CN=C1)N2C(C3=C(N(CC4=CC=C(F)C=C4)N=C3C5=CC=CC=C5)C2=O)C6=CC=C(Br)C=C6