PLM-101 hydrochloride is a synthetic derivative of indirubin and potent, dual FLT3/RET inhibitor with IC50 of 0.565 nM and 0.849 nM for FLT3-ITD and RET kinase respectively.
PLM-101 inhibits the proliferation of Ba/F3 cells expressing FLT3-ITD-mutant kinases at the nanomolar (nM) concentration levels.
PLM-101 exhibits robust inhibitory activity against FLT3 D835Y and F691L secondary mutants.
PLM-101 exhibits anti-proliferation activities of PLM-101 against FLT3-ITD-positive AML cell lines (MV4–11, MOLM-14, and MOLM-13, IC50=3.26, 10.47 and 9.64 nM).
PLM-101 (3-100 nM) induces apoptosis and cell cycle arrest in FLT3-ITD-positive AML cell lines.
PLM-101 exerts anti-leukemic activity by inhibiting the signal transduction of the FLT3-ITD mutant protein, via inhibition of PI3K and Ras/ERK signaling pathways.
PLM-101 activates the autophagy degradation pathway, leading to degradation of both RET and FLT3, and additional inhibition of FLT3 sub-pathway activation.
PLM-101 (3-20 mg/kg, oral) demonstrates anti-leukemic effect in vivo orthotopic xenograft model.