Title: “Discovery of MORF-627, an orally bioavailable, selective avb6 integrin antagonist for the treatment of fibrotic disease”
Organized by the Medicinal Chemistry Section
of the Northeastern Section, American Chemical Society (NESACS)
Thursday –September 15th, 2022
Register for the September Webinar meeting at:
Abstract: The heterodimeric transmembrane receptor, integrin αvb6 is a promising potential target for thetreatment of idiopathic pulmonary fibrosis (IPF) and other fibrotic diseases. In this talk, we will describe the discovery of MORF-627, an orally bioavailable, selective avb6 integrin antagonist with activity in preclinical models of IPF. Optimization of early non-selective hits was accomplished via our MiNT platform, which integrates broad in vitro assay profiling, high-resolution X-ray co-crystal structure determination and in silico potency prediction using Free Energy Perturbation (FEP), to deliver a candidate with potency and pharmacokinetic (P.K.) properties that support a low projected human dose.
Biography: Dr. James E. Dowling earned a B.S. in Chemistry from the University of Massachusetts at Boston under the mentorship of Prof. J.-P. Anselme and completed his Ph.D. work in heterocyclic chemistry with E.C. Taylor at Princeton. He began his medicinal chemistry career at Biogen as a member of the team that delivered Adentri, a selective Adenosine A1 receptor antagonist for the treatment of congestive heart failure. He moved to the oncology group at AstraZeneca in 2006 and worked extensively in the hit-to-lead space, applying fragment-based and encoded library approaches on a range of oncology targets, including the PIM kinase inhibitor AZD-1208 and antagonists of Wnt pathway signaling. In 2017 Jim joined Morphic to take up the challenge of developing oral integrin antagonists for the treatment of diseases with high unmet medical need.
Symposium Organizing Committee: Brian Aquila, Mark Ashwell, Scott Edmondson, Dan Elbaum, Sara Buhrlage, Paul Greenspan, Adrian Hobson, Blaise Lippa, Lisa Marcaurelle, Min Lu, Kap-Sun Yeung, Andrew Scholte, Mala Gopalsamy, Raj (S.B.) Rajur (Chair)