BMS-986224 / BMS - LARVOL DELTA

Identification of 6-Hydroxypyrimidin-4(1H)-one-3-carboxamides as Potent and Orally Active APJ Receptor Agonists. (PubMed, ACS Med Chem Lett) - "Recently we disclosed clinical lead BMS-986224 (1), a C3 oxadiazole pyridinone APJ receptor agonist with robust pharmacodynamic effects similar to (Pyr)apelin-13 in an acute rat pressure-volume loop model. Herein we describe the structure-activity relationship of the carboxamides as oxadiazole bioisosteres at C3 of the pyridinone core and C5 of the respective pyrimidinone core. This study led to the identification of structurally differentiated 6-hydroxypyrimidin-4(1H)-one-3-carboxamide 14a with pharmacodynamic effects comparable to those of compound 1."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

In Vitro and In Vivo Evaluation of a Small-Molecule APJ (Apelin Receptor) Agonist, BMS-986224, as a Potential Treatment for Heart Failure. (PubMed, Circ Heart Fail) - "We identify a novel, potent, and orally bioavailable nonpeptidic APJ agonist that closely recapitulates the signaling properties of (Pyr) apelin-13. We show that oral APJ agonist administration induces a sustained increase in cardiac output in the cardiac disease setting and exhibits a differentiated profile from the renin-angiotensin system inhibitor enalapril, supporting further clinical evaluation of BMS-986224 in heart failure."

Journal • Preclinical • Anesthesia • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology

A Study of BMS-986224 in Healthy Subjects and Heart Failure Patients With Reduced Ejection Fraction (clinicaltrials.gov) - P1; N=199; Terminated; Sponsor: Bristol-Myers Squibb; Completed ➔ Terminated; Business objectives have changed

Clinical • Trial termination

A Study of BMS-986224 in Healthy Subjects and Heart Failure Patients With Reduced Ejection Fraction (clinicaltrials.gov) - P1; N=199; Completed; Sponsor: Bristol-Myers Squibb; Active, not recruiting ➔ Completed; Trial completion date: Oct 2019 ➔ Apr 2019

Clinical • Trial completion • Trial completion date

A Study of BMS-986224 in Healthy Subjects and Heart Failure Patients With Reduced Ejection Fraction (clinicaltrials.gov) - P1; N=262; Active, not recruiting; Sponsor: Bristol-Myers Squibb; Trial primary completion date: Sep 2019 ➔ Apr 2019

Clinical • Trial primary completion date

An Investigational Study to Evaluate Experimental Medication BMS-986224 in Renally Impaired Participants (clinicaltrials.gov) - P1; N=50; Completed; Sponsor: Bristol-Myers Squibb; Recruiting ➔ Completed

Clinical • Trial completion

A Study of BMS-986224 in Healthy Subjects and Heart Failure Patients With Reduced Ejection Fraction (clinicaltrials.gov) - P1; N=262; Active, not recruiting; Sponsor: Bristol-Myers Squibb; Trial completion date: May 2019 ➔ Oct 2019; Trial primary completion date: May 2019 ➔ Sep 2019

Clinical • Trial completion date • Trial primary completion date