11dec4:00 pm5:00 pmDepartment of Pharmacology Seminars: Harris Gelbard, MD, PhD Found in translation, the strange but true story of how URMC-099 came to be4:00 pm - 5:00 pm(GMT+00:00)

Event Details

Harris A. Gelbard, M.D., Ph.D., Professor and Director, Center for Neurotherapeutics Discovery, Departments of Neurology, Pediatrics, Neuroscience and Microbiology and Immunology University of Rochester Medical Center   Abstract The design and construction of small molecule kinase inhibitors for neurodegenerative disease has traditionally been met with ambivalence because of the concern for off-target effects in the central nervous system (CNS).  Mixed lineage kinase (MLK) inhibitors are serine-threonine protein kinases that regulate signaling by the c-Jun amino-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways.  I will describe our rationale for reverse-engineering the development compound in a failed Phase II trial for Parkinson’s disease to create an entirely new class of “selectively non-selective” MLK3 inhibitors.  One of these, URMC-099, is now in development, approximately halfway through IND-enabling studies for the FDA.  While we originally developed this compound to treat another neurologic entity known as HIV-1 associated neurocognitive disorders (HAND), converging lines of evidence in in vitro and in vivo models from both CNS and peripheral diseases with an inflammatory component have considerably broadened the therapeutic possibilities for this class of compounds.  In particular, I will touch upon collaborative work for an eradication strategy for persistent HIV-1 infection; post-operative cognitive dysfunction (POCD), multiple sclerosis (MS) and non-alcoholic steatohepatosis (NASH).   CONTACT: Liz Barrera Murphy 312.503.4892 liz.barrera@northwestern.edu



(Monday) 4:00 pm - 5:00 pm(GMT+00:00)