LBW242

LBW242, a 3-mer and Smac mimetic, is a potent and orally active proapoptotic IAP inhibitor. LBW242 shows effects on mutant FLT3-expressing cells. LBW242 has activity against multiple myeloma, and potentiates TRAIL- and anticancer drug-mediated cell death of ovarian cancer cells^[1][2]. In Vitro: LBW242 is a 3-mer and Smac mimetic, based on the ability of the NH2-terminal seven amino acids of Smac to neutralize the BIR3 domain of X-chromosome-linked IAP (XIAP). LBW242 partially inhibits the growth of mutant FLT3-expressing lines, MV4;11 at 1 μM^[1].
LBW242 kills cells in a manner strictly dependent on caspases, and death is accompanied by PARP cleavage, Annexin positivity, and accumulation of cells in sub-G1^[1]. LBW242 (0-0.1 μM; 3 days) inhibits a panel of PKC412-sensitive or PKC412-resistant, mutant FLT3-expressing Ba/F3 lines The IC₅₀ values ranged from 0.5 to >1 μM^[1]. In Vivo: LBW242 (50 mg/kg; p.o.; daily for 10 days) reduces tumor burden^[1].