AXL and MERTK are members of TAM (TYRO3, AXL and MERTK) receptor t
yrosine kinases and play important roles in tumor progression, metastasis,
drug resistance and immune evasion. Thus, dual inhibition of AXL and ME
RTK in the tumor and tumor immune microenvironment would enhance a
nti-tumor efficacy and boost anti-tumor immune responses. Utilizing our
proprietary small molecule tyrosine kinase inhibitors compound library an
d structure-based drug design by protein crystallography approach, we h
ave identified an orally bioavailable AXL and MERTK dual kinase inhibitor
BPR5K230 with potent AXL and MERTK inhibitory activities and selectivity
over TYRO3. BPR5K230 demonstrated in vivo anti-tumor efficacy and imm
unomodulatory activities; the anti-tumor effect of BPR5K230 was more efficacious than that of the current Phase II clinical trial agent Ono-7475. The
current invention is intended to use in late stage triple negative breast can
cer, lung cancer and liver cancer.