Bemcentinib Tyrosine-protein kinase receptor UFO (Axl) inhibitor Treatment of cancer

摘要

Increased expression of Axl has been reported in various cancers including colon, esophageal, thyroid, breast, lung, liver and astrocytoma-glioblastoma. Cancer resistance to tyrosine kinase inhibitors and other chemotherapeutics has been correlated with aberrant expression of Axl. These findings support the development of Axl inhibitors in combination with targeted agents to tackle acquired resistance and high Axl levels. Bemcentinib (BGB-324, R-428) is an oral, potent and selective small-molecule inhibitor of Axl kinase in vitro with IC50 values in the low nanomolar range. In preclinical studies, bemcentinib demonstrated efficacy across multiple cancer models. It has also shown a favorable safety profile in clinical studies in cancer patients, and encouraging activity in acute myeloid leukemia (AML) and non-small cell lung cancer (NSCLC). Currently, there are phase II studies with bemcentinib ongoing in advanced NSCLC, triple-negative breast cancer, AML and myelodysplastic syndromes, and metastatic melanoma. Orphan drug designation was granted by the U.S. Food and Drug Administration for the treatment of AML.