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[1].

Research Areas >> Cancer

Signaling Pathways >> Apoptosis >> IAP

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FLT3

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 1μM[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]. Cell Viability Assay[1] Cell Line: FLT3-ITD-Ba/F3 cells and mutant FLT3-expressing cells, A627T-FLT3-Ba/F3, F691IFLT3-Ba/F3, and N676D-FLT3-Ba/F3 cells Concentration: 0.001, 0.01, 0.1 μM Incubation Time: 3 days Result: Inhibited a panel of PKC412-sensitive or PKC412-resistant, mutant FLT3-expressing Ba/F3 lines The IC50 values ranged from 0.5 to >1 μM .

LBW242 (50 mg/kg; p.o.; daily for 10 days) reduces tumor burden[1]. Animal Model: NCR nude mice were inoculated with FLT3-ITD-Ba/F3 cells[1] Dosage: 50 mg/kg Administration: Oral gavage; daily for 10 days Result: Effective in reducing tumor burden.

[1]. Weisberg E, et al. Potentiation of antileukemic therapies by Smac mimetic, LBW242: effects on mutant FLT3-expressing cells. Mol Cancer Ther. 2007 Jul;6(7):1951-61.