LDC1267

LDC1267 is a highly selective TAM(Tyro3, Axl and Mer) kinase inhibitor with IC50 of <5 nM/8 nM/29 nM for Tyro3,Axl and Mer respectively.IC50 value: <5 nM/8 nM/29 nM(Tyro3/Axl/Mer) [1]Target: TAM kinase inhibitorin vitro: LDC1267 preferentially inhibits Tyro3,Axl andMer at lownanomolarity, as determined by tracer-based binding assays. Treatment of NKG2D activated NK cells with LDC1267 indeed abolished the inhibitory effects of Gas6 stimulation;LDC1267 had no apparent additional effect in Cbl-b-deficient NK cells. in vivo: wild-type mice treated with LDC1267 showed enhanced cytotoxicity towardsRMAcells overexpressing the NKG2D ligand Rae-1 (RMA-Rae1) to the same extent as C373AKI/KI mice, but had no effect on the already enhanced NK cytotoxicity in Cbl-b-mutant mice. Challenged mice with B16F10 melanoma followedby intraperitoneal LDC1267 treatment. LDC1267 markedly reduced metastatic spreading ofmelanomas; NK1.1 depletion abolished the therapeutic benefits of LDC1267.

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> TAM Receptor

Research Areas >> Inflammation/Immunology

[1]. Paolino M, et al. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature. 2014 Mar 27;507(7493):508-12.

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