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 SquibbRobert F. Kaltenbach - Bristol-Myers SquibbHao Zhang - Bristol-Myers SquibbJun Shi - Bristol-Myers SquibbShiwei Tao - Bristol-Myers SquibbJun Li - Bristol-Myers SquibbLawrence J. Kennedy - Bristol-Myers SquibbSteven J. Walker - Bristol-Myers SquibbYan Shi - Bristol-Myers SquibbYing Wang - Bristol-Myers SquibbSuresh Dhanusu - BioconRamesh 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 SquibbDaniel Smith - Bristol-Myers SquibbSubramaniam Krishnananthan - Bristol-Myers SquibbJianqing Li - Bristol-Myers SquibbTao Wang - Bristol-Myers SquibbRebekah Heiry - Bristol-Myers SquibbChi Shing Sum - Bristol-Myers SquibbStephen S. Kalinowski - Bristol-Myers SquibbChen-Pin Hung - Bristol-Myers SquibbChing-Hsuen Chu - Bristol-Myers SquibbAnthony Azzara - Bristol-Myers SquibbMilinda Ziegler - Bristol-Myers SquibbLisa Burns - Bristol-Myers SquibbBradley A. Zinker - Bristol-Myers SquibbStephanie Boehm - Bristol-Myers SquibbJoseph Taylor - Bristol-Myers SquibbJulia Sapuppo - Bristol-Myers SquibbKathy Mosure - Bristol-Myers SquibbGerry Everlof - Bristol-Myers SquibbVictor Guarino - Bristol-Myers SquibbLisa Zhang - Bristol-Myers SquibbYanou Yang - Bristol-Myers SquibbQian Ruan - Bristol-Myers SquibbCarrie Xu - Bristol-Myers SquibbAtsu Apedo - Bristol-Myers SquibbSarah C. Traeger - Bristol-Myers SquibbMary Ellen Cvijic - Bristol-Myers SquibbKimberley A. Lentz - Bristol-Myers SquibbGiridhar Tirucherai - Bristol-Myers SquibbLakshmi Sivaraman - Bristol-Myers SquibbJeffrey Robl - Bristol-Myers SquibbBruce A. Ellsworth - Bristol-Myers SquibbGlenn Rosen - Bristol-Myers SquibbDavid A. Gordon - Bristol-Myers SquibbMatthew G. Soars - Bristol-Myers SquibbMichael Gill - Bristol-Myers SquibbBrian J. Murphy - Bristol-Myers Squibb
- 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