Proteoform Thursday: Jeff Agar presents “Intact Mass Assay Enables Animal Studies of Covalent Drug-Target Binding and Determination of PK/PD Parameters”
March 20, 2025 11:00 AM in Eastern Time (US and Canada)
Until recently, Pharma avoided rational covalent drug development due to safety concerns and the lack of suitable bioanalytical methods. During this time, enough covalent drugs were discovered serendipitously by phenotypic assays and traditional medicine that covalent drugs still comprise 30% of the market. A class of important targets, termed undruggable targets, may only be accessible to covalent drugs, resulting in major recent covalent drug discovery efforts. Here we present bioanalytical methods to quantify drug-target engagement from in vivo samples, and develop the mathematical framework “iPK/PD” for assigning adsorption, distribution, metabolism, and excretion (ADME) parameters.