Journal article
Discovery of an Oxycyclohexyl Acid Lysophosphatidic Acid Receptor 1 (LPA1) Antagonist BMS-986278 for the Treatment of Pulmonary Fibrotic Diseases
Journal of medicinal chemistry, v 64(21), pp 15549-15581
11 Nov 2021
PMID: 34709814
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The oxycyclohexyl acid BMS-986278 (33) is a potent lysophosphatidic acid receptor 1 (LPA1) antagonist, with a human LPA1 Kb of 6.9 nM. The structure-activity relationship (SAR) studies starting from the LPA1 antagonist clinical compound BMS-986020 (1), which culminated in the discovery of 33, are discussed. The detailed in vitro and in vivo preclinical pharmacology profiles of 33, as well as its pharmacokinetics/metabolism profile, are described. On the basis of its in vivo efficacy in rodent chronic lung fibrosis models and excellent overall ADME (absorption, distribution, metabolism, excretion) properties in multiple preclinical species, 33 was advanced into clinical trials, including an ongoing Phase 2 clinical trial in patients with lung fibrosis (NCT04308681).
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Details
- Title
- Discovery of an Oxycyclohexyl Acid Lysophosphatidic Acid Receptor 1 (LPA1) Antagonist BMS-986278 for the Treatment of Pulmonary Fibrotic Diseases
- Creators
- Peter T. W. Cheng - Bristol-Myers Squibb (United States)Robert F. Kaltenbach - Bristol-Myers Squibb (United States)Hao Zhang - Bristol-Myers Squibb (India)Jun Shi - Bristol-Myers Squibb (United States)Shiwei Tao - Bristol-Myers Squibb (United States)Jun Li - Bristol-Myers Squibb (United States)Lawrence J. Kennedy - Bristol-Myers Squibb (United States)Steven J. Walker - Bristol-Myers Squibb (United States)Yan Shi - Bristol-Myers Squibb (United States)Ying Wang - Bristol-Myers Squibb (United States)Suresh Dhanusu - Biocon (India)Ramesh Reddigunta - Biocon Bristol Myers Squibb Res & Dev Ctr, Bangalore 560099, Karnataka, IndiaSelvakumar Kumaravel - Biocon Bristol Myers Squibb Res & Dev Ctr, Bangalore 560099, Karnataka, IndiaSutjano Jusuf - Bristol-Myers Squibb (United States)Daniel Smith - Bristol-Myers Squibb (United States)Subramaniam Krishnananthan - Bristol-Myers Squibb (United States)Jianqing Li - Bristol-Myers Squibb (United States)Tao Wang - Bristol-Myers Squibb (United States)Rebekah Heiry - Bristol-Myers Squibb (United States)Chi Shing Sum - Bristol-Myers Squibb (United States)Stephen S. Kalinowski - Bristol-Myers Squibb (United States)Chen-Pin Hung - Bristol-Myers Squibb (United States)Ching-Hsuen Chu - Bristol-Myers Squibb (United States)Anthony Azzara - Bristol-Myers Squibb (United States)Milinda Ziegler - Bristol-Myers Squibb (United States)Lisa Burns - Bristol-Myers Squibb (United States)Bradley A. Zinker - Bristol-Myers Squibb (United States)Stephanie Boehm - Bristol-Myers Squibb (United States)Joseph Taylor - Bristol-Myers Squibb (United States)Julia Sapuppo - Bristol-Myers Squibb (United States)Kathy Mosure - Bristol-Myers Squibb (United States)Gerry Everlof - Bristol-Myers Squibb (United States)Victor Guarino - Bristol-Myers Squibb (United States)Lisa Zhang - Bristol-Myers Squibb (United States)Yanou Yang - Bristol-Myers Squibb (United States)Qian Ruan - Bristol-Myers Squibb (United States)Carrie Xu - Bristol-Myers Squibb (United States)Atsu Apedo - Bristol-Myers Squibb (United States)Sarah C. Traeger - Bristol-Myers Squibb (United States)Mary Ellen Cvijic - Bristol-Myers Squibb (United States)Kimberley A. Lentz - Bristol-Myers Squibb (United States)Giridhar Tirucherai - Bristol-Myers Squibb (United States)Lakshmi Sivaraman - Bristol-Myers Squibb (United States)Jeffrey Robl - Bristol-Myers Squibb (United States)Bruce A. Ellsworth - Bristol-Myers Squibb (United States)Glenn Rosen - Bristol-Myers Squibb (United States)David A. Gordon - Bristol-Myers Squibb (United States)Matthew G. Soars - Bristol-Myers Squibb (United States)Michael Gill - Bristol-Myers Squibb (United States)Brian J. Murphy - Bristol-Myers Squibb (United States)
- Publication Details
- Journal of medicinal chemistry, v 64(21), pp 15549-15581
- Publisher
- Amer Chemical Soc
- Number of pages
- 33
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000718382200004
- Scopus ID
- 2-s2.0-85118879366
- Other Identifier
- 991021902525604721
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- Collaboration types
- International collaboration
- Web of Science research areas
- Chemistry, Medicinal