bmx-in-1 and Prostatic-Neoplasms

BMX is a member of the TEC family of nonreceptor tyrosine kinases. We have used structure-based drug design in conjunction with kinome profiling to develop a potent, selective, and irreversible BMX kinase inhibitor, BMX-IN-1, which covalently modifies Cys496. BMX-IN-1 inhibits the proliferation of Tel-BMX-transformed Ba/F3 cells at two digit nanomolar concentrations but requires single digit micromolar concentrations to inhibit the proliferation of prostate cancer cell lines. Using a combinatorial kinase inhibitor screening strategy, we discovered that the allosteric Akt inhibitor, MK2206, is able to potentiate BMX inhibitor's antiproliferation efficacy against prostate cancer cells.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Combinatorial Chemistry Techniques; Drug Discovery; Flow Cytometry; Humans; Inhibitory Concentration 50; Male; Models, Molecular; Prostatic Neoplasms; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyridones; Sulfonamides