ACK1 integrates signals from various receptor tyrosine kinases, e.g. EGFR, PDGFR, Insulin receptor (IR), HER-2 and FGFR. These kinases activates ACk1 in prostate and breast cancers. Further, ACK1 is amplified in 40% of lung cancers. However, no ACK1 inhibitor has so far made it to clinical trial.
Identification of the novel ACK1 inhibitor, (R)-9b
We generated a new class of small molecule ACK1 inhibitor (R)-9b, that has excellent drug-like properties. (R)-9b suppressed proliferation of various prostate, breast and lung xenograft tumor growth.
Crystal structure of (R)-9b bound to ACK1
Recently with our collaborators, we have solved the crystal structure of (R)-9b bound to ACK1 kinase domain.
Pre-IND GLP-Tox studies with (R)-9b
(R)-9b has excellent ADME properties and exhibited no toxicity in rats even at high dosage. It also has oral efficacy.
Clinical Trial of ACK1 inhibitor, (R)-9b
Efforts are underway for the clinical trials of (R)-9b in prostate and breast cancer. Dr. Nupam Mahajan (nupam@wustl.edu) can be contacted by interested parties.
