LDC1267

• CAT Number: I001392
• CAS Number: 1361030-48-9
• Molecular Formula: C30H26F2N4O5
• Molecular Weight: 560.558
• Purity: ≥95%
• Synonyms: N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluoro-2-methylphenyl)-1H-pyrazole-3-carboxamide
• Target: Axl
• Solubility: DMSO: ≥ 42 mg/mL
• Storage: Store at -20°C
• IC50: <5 nM/8 nM/29 nM(Tyro3/Axl/Mer) [1]
• IUPAC Name: N-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-4-ethoxy-1-(4-fluoro-2-methylphenyl)pyrazole-3-carboxamide
• InChI: InChI=1S/C30H26F2N4O5/c1-5-40-28-16-36(23-8-6-18(31)12-17(23)2)35-29(28)30(37)34-19-7-9-25(21(32)13-19)41-24-10-11-33-22-15-27(39-4)26(38-3)14-20(22)24/h6-16H,5H2,1-4H3,(H,34,37)
• InChIKey: ISPBCAXOSOLFME-UHFFFAOYSA-N
• SMILES: CCOC1=CN(N=C1C(=O)NC2=CC(=C(C=C2)OC3=C4C=C(C(=CC4=NC=C3)OC)OC)F)C5=C(C=C(C=C5)F)C

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.

Reference

[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.