BMS Lecture, Presented by Prof. Steven Townsend, Vanderbilt University
New Strategies to Prevent Premature Birth and Break Strong Bonds
Presented by Prof. Steven Townsend
Hosted by Prof. Makeda Tekle-Smith
Abstract:
Carbohydrates are the most abundant organic molecules on earth and are critical to a myriad of biological processes. The Vanderbilt Laboratory for Glycoscience uses a blend of synthetic organic chemistry and microbiology to elucidate the biological roles of carbohydrates, with a foci on advances in chemical synthesis and learning new mechanistic concepts. Our discussion will be divided into two categories: (1) the synthesis of structurally and biologically compelling complex carbohydrates, and (2) application of the host defense properties of human milk.
Discovery of afimetoran, a first-in-class small molecule dual antagonist of TLR7/8 for the treatment of lupus
Presented by Dr. Trevor Sherwood
Bio:
Trevor grew up in New Hampshire and earned his B.S. in chemistry at Rensselaer Polytechnic Institute in upstate New York in 2008 working with Prof. Robert J. Linhardt on the synthesis of carbohydrates. He then traveled south to New York City where he earned his Ph.D. in 2013 in the laboratory of Prof. Scott A. Snyder at Columbia University, where he completed multiple total syntheses of alkaloid and polyphenolic natural products. In 2013, Trevor joined the Bristol Myers Squibb Discovery Chemistry Immunology group in Princeton, NJ, where he has performed research on a variety of different target classes for the treatment of autoimmune disorders and currently leads multiple drug discovery programs. Trevor also researches applications for photoredox catalysis in medicinal chemistry with a particular focus on cross-coupling chemistry. He is passionate about LGBTQ representation in chemistry and recently organized a session at the 2024 ACS National Meeting featuring presentations from LGBTQ medicinal chemists.
Abstract:
The innate immune system employs toll-like receptors (TLRs) to identify signs of cellular stress and infection through the recognition of damage-associated and pathogen-associated molecular patterns, resulting in upregulation of immune pathways. Autoimmunity can result from the recognition of self-motifs as foreign by the TLRs, with TLR7 and TLR8 being associated with human autoimmune diseases such as lupus, psoriasis, and arthritis. Our program to develop selective dual antagonists of TLR7/8 started with an indole scaffold identified through a high-throughput screening campaign. Elaboration of this indole chemical series aided by structure-based design led to selective dual antagonists of TLR7/8 with progressible properties. One of the analogs discovered in our program, afimetoran, was selected as a development candidate and is currently in clinical trials for lupus. This presentation will detail the explored SAR of the indole substituents, synthetic strategies employed during our campaign, and in vivo performance for afimetoran.