Discovery and Drug Development Progress for MTI-101, a Cyclic Beta-hairpin Peptidomimetic.
Mark McLaughlin
Senior Member, Moffitt Cancer Center
MTI-101 targets CD44, which is a cell adhesion molecule required for homing to the bone and we reasoned that MTI-101 would show its best activity against cancers that home that bone like MM (multiple myeloma). Indeed, MTI-101 causes programmed cell necrosis of MM cells in vitro, has excellent in vivo activity as a single agent and when combined with bortezomib with no overt toxicity. MTI-101 also reduces bone metastases as a single agent and eliminates bone metastases when combined with erlotinib against EGFR-driven lung cancer in vivo. MTI-101 also reduces primary lung tumors as single agent and eliminates them when combined with erlotinib in these same in vivo models. How MTI-101 was discovered, more about its target and mechanism of action, and its development to date will be presented.
Mark McLaughlin is a synthetic organic/peptide chemist that earned his Ph.D. from Georgia Tech and completed postdoctoral training at Rice University and Ohio State University. He started his career at the department of chemistry at LSU in Baton Rouge, Louisiana, where he rose through the ranks to full professor and contributed to the technology being developed by Esperance Pharmaceuticals. He later moved to Tampa, Florida as Professor of Chemistry at the University of South Florida, Senior Member of the Drug Discovery Department at the Moffitt Cancer Center, and more recently co-founded Modulation Therapeutics Incorporated where he is currently Executive Vice President and Treasurer. He designs and synthesizes peptidic and fully non-peptidic beta-sheet and alpha-helical mimics to block protein-protein interactions and that interest has led to the discovery of MTI-101, a cyclic beta-hairpin peptidomimetic that is the lead candidate for Modulation Therapeutics and that will be the focus of his presentation at the Boulder Symposium.