AXL and MERTK are members of TAM (TYRO3, AXL and MERTK) receptor tyrosine kinases. Both AXL and MERTK play important roles in tumor progression, metastasis, drug resistance and immune evasion. This invention describes the discovery and development of BPR5K230, a potent, orally bioavailable AXL and MERTK dual kinase inhibitor with anti-tumor efficacy and immunomodulatory activities.

We have identified a potent AXL and MERTK dual kinase inhibitor BPR5K230 from our proprietary small molecule kinase inhibitors compound library and optimized through structure-based drug design by protein crystallography approach. BPR5K230 produced greater anti-tumor efficacy than either AXL or MERTK mono-targeted agent used alone, verifying BPR5K230’s dual AXL and MERTK inhibitory activities.

Novel AXL and MERTK dual kinase inhibitors use one single chemical entity with dual functions to simultaneously inhibit AXL and MERTK signaling in the tumor and tumor immune suppressive microenvironment, thereby enhancing anti-tumor efficacy and boosting anti-tumor immune responses. Novel AXL and MERTK dual kinase inhibitors can be positioned in kinase inhibitors markets, targeted cancer therapy market and immuno-oncology market.