title: Discovery of AZD2716: A Novel Secreted Phospholipase A2(sPLA2) Inhibitor for the Treatment of Coronary Artery Disease.
abstract: Expedited structure-based optimization of the initial fragment hit1led to the design of (R)-7(AZD2716) a novel, potent secreted phospholipase A2(sPLA2) inhibitor with excellent preclinical pharmacokinetic properties across species, clearin vivoefficacy, and minimized safety risk. Based on accumulated profiling data, (R)-7was selected as a clinical candidate for the treatment of coronary artery disease.
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Fabrizio
authors: F
authors: Giordanetto
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Daniel
authors: D
authors: Pettersen
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Ingemar
authors: I
authors: Starke
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Peter
authors: P
authors: Nordberg
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Mikael
authors: M
authors: Dahlström
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Laurent
authors: L
authors: Knerr
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Nidhal
authors: N
authors: Selmi
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Birgitta
authors: B
authors: Rosengren
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Lars-Olof
authors: LO
authors: Larsson
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Jenny
authors: J
authors: Sandmark
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Marie
authors: M
authors: Castaldo
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Niek
authors: N
authors: Dekker
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Ulla
authors: U
authors: Karlsson
authors: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit Departments of Medicinal Chemistry, Bioscience, DMPK, Discovery Sciences Departments of Structure & Biophysics, Reagents and Assay Development, and Screening Sciences and Sample Management, Astrazeneca, Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors: Eva
authors: E
authors: Hurt-Camejo
keywords: Secreted phospholipase A2; atherosclerosis; coronary artery disease; fragment screening; fragment-based drug discovery; inhibitor; sPLA2