Related Experiment Video
Updated: Jul 10, 2026

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
Published on: February 28, 2019
MCH-R1 antagonists: what is keeping most research programs away from the clinic?
José L Méndez-Andino1, John A Wos
1Procter & Gamble Pharmaceuticals, New Technology Development, 8700 Mason-Montgomery Road, Mason, OH 45039, USA. mendezandino.jl@pg.com
Abstract:
Despite the high number of drug-discovery programs dedicated to finding small-molecule MCH-R1 antagonists for the treatment of obesity and/or mood disorders, a very limited number of these have progressed into the clinic. Beyond the common challenges in drug design related to ADME and safety profiles, cardiovascular risk involving hERG binding and the potential for subsequent drug-induced QTc prolongation has been a major hurdle for a significant number of MCH-R1 research programs. Many of these programs have evolved, and effectively designed MCH antagonists having decreased hERG-binding affinity have emerged. Currently, however, only a selected few candidates have progressed to clinical development. Drug-design strategies, in vivo efficacy, ADME, and cardiovascular safety profiles for a selection of MCH-R1 antagonist research programs are discussed ahead.
Related Concept Videos
Direct-Acting Cholinergic Agonists: Therapeutic Uses
Drugs Acting on Autonomic Ganglia: Blockers
Cholinergic Antagonists: Chemistry and Structure-Activity Relationship
Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally, α1-blockers effectively address urinary obstruction...
Antiasthma Drugs: Muscarinic Receptor Antagonists
Antimuscarinic agents compete with ACh for the same binding site on the muscarinic receptors. By binding to these receptors, they inhibit the downstream effects of ACh and block the parasympathetic...
Preclinical Development: Overview