Registration is required for this free webinar
Hosted by the SOT Drug Discovery Specialty Section
Join us in hearing from the 2025 DDTSS Award Winners! This webinar will highlight our Paper of the Year, "Discovery of TRPA1 Antagonist GDC-6599: Derisking Preclinical Toxicity and Aldehyde Oxidase Metabolism with a Potential First-in-Class Therapy for Respiratory Disease," published by Satoko Kiyota et al. and presentations by four of our trainee award winners. Check out the Paper of the Year abstract and trainee titles below!
2025 Drug Discovery Paper of the Year:
Discovery of TRPA1 Antagonist GDC-6599: Derisking Preclinical Toxicity and Aldehyde Oxidase Metabolism with a Potential First-in-Class Therapy for Respiratory Disease
Satoko Kiyota, PhD, Distinguished Scientist, Genentech, Inc.
Transient receptor potential ankyrin 1 (TRPA1) is a nonselective calcium ion channel highly expressed in the primary sensory neurons, functioning as a polymodal sensor for exogenous and endogenous stimuli, and has been implicated in neuropathic pain and respiratory disease. Herein, we describe the optimization of potent, selective, and orally bioavailable TRPA1 small molecule antagonists with strong in vivo target engagement in rodent models. Several lead molecules in preclinical single- and short-term repeat-dose toxicity studies exhibited profound prolongation of coagulation parameters. Based on a thorough investigative toxicology and clinical pathology analysis, anticoagulation effects in vivo are hypothesized to be manifested by a metabolite─generated by aldehyde oxidase (AO)─possessing a similar pharmacophore to known anticoagulants (i.e., coumarins, indandiones). Further optimization to block AO-mediated metabolism yielded compounds that ameliorated coagulation effects in vivo, resulting in the discovery and advancement of clinical candidate GDC-6599, currently in Phase II clinical trials for respiratory indications.
Drug Discovery Trainee Award Winners:
Diploid Hepatocytes Resist Acetaminophen-Induced Acute Liver Injury
Sierra Wilson, PhD Candidate, University of Pittsburgh School of Medicine
Integrating Transporter Data and Machine Learning Approaches to Predict Drug Transport across the Placental Barrier
Tong Wang, PhD, Rowan University
Selective Receptor Modulation During Melatonin Renoprotection Against Vancomycin Toxicity
Christine Kim, PharmD, Rutgers University
Application of Machine Learning and Mechanistic Modeling to Predict Intravenous Pharmacokinetic Profiles in Humans
Xuelian Jia, PhD, Tulane University School of Medicine