生物活性

• 描述Classified basing on their distinctive domain structure and the unique KW(I/L)A(I/L)ES sequence in their catalytic domain, Tyro3, Axl, and Mer, compose the TAM subfamily of receptor tyrosine kinases (RTK). This subfamily of RTKs transduce signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. These RTKs regulate many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells. LDC1267 is a highly selective kinase inhibitor binding to the TAM receptor tyrosine kinases. As determined by tracer-based binding assays, the IC50s of LDC1267 for Tyro3, Axl and Mer were <5 nM, 8 nM and 29 nM, respectively. In a quantitative chemical proteomics approach performed to test the cellular selectivity of LDC1267, elution with up to 10 μM LDC1267 identified Axl and Met as the two high affinity protein targets, while Tyro3 was not expressed in that experiment system. Additionally, the IC50 value of LDC1267 for cellular inhibition of Axl phosphorylation was about 10 nM. In cell proliferation assays, 72h treatment of LDC1267 moderately affected proliferation of 11 cell lines with the best IC50 value at about 5 μM. The average IC50 value for those 11 cell lines was about 15 μM. In animal studies of the breast cancer 4T1 metastases experiment, mice were treated with LDC1267 using daily oral gavage at the dose of 100 mg/kg, The results were that LDC1267 significantly reduced 4T1 liver micro-metastases.

• 动物研究
  剂量	Mice: 20 mg/kg[1] (i.p.); 100 mg/kg[1] (p.o.)
  给药途径	i.p., p.o.