MOMA-341 is a chemically distinct, potent, and selective clinical stage covalent inhibitor of WRN. Leveraging MOMA's KNOWMATIC platform and the presence of cysteine 727 in an allosteric binding pocket, covalent inhibitors were designed to achieve high potency. Optimization was based on precise refinement of covalent warhead trajectory, compound rigidity, and improvement of binding affinity to drive high kinact/KI. Optimization of potency and ADME properties, guided by in silico prediction of in vivo target occupancy, led to the discovery of MOMA-341, which demonstrates tumor regression at low doses in MSI-H mouse xenograft models. MOMA-341 is currently in clinical development.

GPR61 is a brain-enriched class A orphan GPCR that may be involved in appetite and body weight modulation. Herein we describe our medicinal chemistry efforts in discovering a class of potent, selective, and brain-penetrant GPR61 inverse agonists from an HTS hit. Cryo-EM structures reveal this class of inverse agonists binds to an induced intracellular allosteric pocket and abolishes GPR61 activity by disrupting its interactions with G protein.

Oral small-molecule GLP-1 agonists with engineered signaling bias could deliver the metabolic efficacy of injectable GLP-1s with reduced side effects. Conventional approaches treat the receptor as a static cryo-EM snapshot, producing leads that bind but fail to achieve desired signaling profiles. DEEP DISCOVERY (US Patent Nos. 12,450,409 and 12,424,300) learns structure-function correlation across the GPCR superfamily—integrating structural, ligand, and functional data telescopically—then uses CAM-guided saliency to infer receptor conformations biased toward Gs-coupled signaling. From these conformations, the platform generates ligands that stabilize the desired state. We present our orally bioavailable GLP-1 lead advancing toward pre-clinical testing.

APJ is a G-protein coupled receptor (GPCR) conducting G-protein and b-arrestin dependent signals which are protective against metabolic diseases and promote muscle regeneration; GLP-1 agonist induces rapid weight loss from losing not only fat but also muscles, a common undesirable effect; co-activation of G-protein dependent signaling of APJ with GLP-1 can preserve muscles while losing weight; YJ-015 discovered by Yogar Therapeutics is a potent APJ agonist biased for activating the G protein-dependent function and demonstrates beneficial effect as an adjuvant to semaglutide on weight loss and muscle preservation in obesity mouse-model.

Economic burden of neurodegenerative diseases exceeded trillions of dollars in 2025. Recently launched biologicals provide marginal benefit. Parkinson’s and Alzheimer’s diseases (PD/AD) are driven by protein aggregation—such as a-synuclein and tau—that disrupts mitochondrial function. Damaged mitochondrial kinase PINK1 phosphorylate ubiquitin that activates parkin ligase to promote mitophagy and autophagy. A potent PINK1/Parkin molecular glue drug to remove protein aggregates and damaged mitochondria and restores mitobiogenesis will be discussed.