Cancer

In vitro, cell culture and mouse studies identified two benzenesulfonamide-based AXL inhibitors that could help treat breast cancer. Chemical synthesis and in vitro enzymatic activity assays of benzenesulfonamide analogs yielded two compounds that inhibited AXL with IC₅₀ values of 27 and 28 nM. In a human triple-negative breast cancer (TNBC) cell line, the compounds inhibited cell migration with IC₅₀ values of 3.3 and 2.5 μM. In a xenograft mouse model of breast cancer, the first compound decreased tumor size and increased survival compared with vehicle. In an orthotopic mouse model of metastatic TNBC, the second compound decreased the number of lung metastases and tumor cell infiltration into regional lymph nodes compared with paclitaxel. Next steps could include testing the compounds in additional models of breast cancer.

Rigel Pharmaceuticals Inc., BerGenBio ASA and Merck & Co. Inc. have bemcentinib (BGB324), a small molecule AXL inhibitor, in Phase II testing for adenocarcinoma of the lung and metastatic TNBC. Rigel and BerGenBio have the compound in Phase II testing for acute myelogenous leukemia (AML) and Phase I/II testing for melanoma, myelodysplastic syndrome (MDS) and non-small cell lung cancer (NSCLC)...