Acetyl-CoA carboxylase (ACC) as a therapeutic target for metabolic syndrome and recent developments in ACC1/2 inhibitors

PS-109-Partial inhibition of de novo lipogenesis with the acetyl-CoA carboxylase inhibitor PF-05221304 does not increase circulating triglycerides in humans and is sufficient to lower steatosis in rats

(2019) William Esler et al.   JOURNAL OF HEPATOLOGY

Human sebum requires de novo lipogenesis, which is increased in acne vulgaris and suppressed by acetyl-CoA carboxylase inhibition

(2019) William P. Esler et al.   Science Translational Medicine

Discovery of a novel olefin derivative as a highly potent and selective acetyl-CoA carboxylase 2 inhibitor with in vivo efficacy

(2018) Yuji Nishiura et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Cancer, obesity and immunometabolism – Connecting the dots

(2018) Lydia Dyck et al.   CANCER LETTERS

Acetyl-CoA Carboxylase Inhibitor GS-0976 for 12 Weeks Reduces Hepatic De Novo Lipogenesis and Steatosis in Patients With Nonalcoholic Steatohepatitis

(2018) Eric J. Lawitz et al.   Clinical Gastroenterology and Hepatology

Su1521 - Preliminary Efficacy and Safety of Acetyl-Coa Carboxylase (ACC) Inhibitor GS-0976 in Patents with Compensated Cirrhosis due to NASH

(2018) Stephen A. Harrison et al.   GASTROENTEROLOGY

Characterization of changes in lipoprotein profiles of patients with nonalcoholic steatohepatitis treated with the acetyl-CoA carboxylase inhibitor GS-0976

(2018) P. Mantry et al.   JOURNAL OF HEPATOLOGY

Safety, tolerability, pharmacokinetics and pharmacodynamics of a liver-targeting ACC inhibitor (PF-05221304) following single and multiple oral doses

(2018) A. Bergman et al.   JOURNAL OF HEPATOLOGY

Discovery of Novel Selective Acetyl-CoA Carboxylase (ACC) 1 Inhibitors

(2018) Ryo Mizojiri et al.   JOURNAL OF MEDICINAL CHEMISTRY

Pathogenesis of Nonalcoholic Steatohepatitis and Hormone-Based Therapeutic Approaches

(2018) Kook Hwan Kim et al.   Frontiers in Endocrinology

Anti-acne drugs in phase 1 and 2 clinical trials

(2017) Christos C. Zouboulis et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Acetyl-coenzyme A carboxylase inhibition reduces de novo lipogenesis in overweight male subjects: A randomized, double-blind, crossover study

(2017) Kathryn Stiede et al.   HEPATOLOGY

Inhibition of Sebum Production with the Acetyl Coenzyme A Carboxylase Inhibitor Olumacostat Glasaretil

(2017) David W. Hunt et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Olumacostat Glasaretil, a Promising Topical Sebum-Suppressing Agent that Affects All Major Pathogenic Factors of Acne Vulgaris

(2017) Bodo C. Melnik   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Olumacostat glasaretil, a novel topical sebum inhibitor, in the treatment of acne vulgaris: A phase IIa, multicenter, randomized, vehicle-controlled study

(2017) Robert Bissonnette et al.   JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

Obesity and hypertension

(2017) Gino Seravalle et al.   PHARMACOLOGICAL RESEARCH

Inhibition of Acetyl-CoA Carboxylase 1 (ACC1) and 2 (ACC2) Reduces Proliferation and De Novo Lipogenesis of EGFRvIII Human Glioblastoma Cells

(2017) Jessica E. C. Jones et al.   PLoS One

Discovery of N -(1-(3-(4-phenoxyphenyl)-1,2,4-oxadiazol-5-yl)ethyl)acetamides as novel acetyl-CoA carboxylase 2 (ACC2) inhibitors with peroxisome proliferator-activated receptor α/δ (PPARα/δ) dual agonistic activity

(2016) Shogo Okazaki et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Molecular modeling study for the design of novel acetyl-CoA carboxylase inhibitors using 3D QSAR, molecular docking and dynamic simulations

(2016) Vivek K. Vyas et al.   JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS

Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats

(2016) Geraldine Harriman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Acetyl-CoA carboxylase inhibitors attenuate WNT and Hedgehog signaling and suppress pancreatic tumor growth

(2016) Elissaveta Petrova et al.   Oncotarget

Nonalcoholic Fatty Liver Disease

(2015) Mary E. Rinella   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Paleo-soraphens: chemical total syntheses and biological studies

(2015) Hai-Hua Lu et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Chemical inhibition of acetyl-CoA carboxylase suppresses self-renewal growth of cancer stem cells

(2015) Bruna Corominas-Faja et al.   Oncotarget

Activation of farnesoid X receptor (FXR) protects against fructose-induced liver steatosis via inflammatory inhibition and ADRP reduction

(2014) Xijun Liu et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Decreasing the Rate of Metabolic Ketone Reduction in the Discovery of a Clinical Acetyl-CoA Carboxylase Inhibitor for the Treatment of Diabetes

(2014) David A. Griffith et al.   JOURNAL OF MEDICINAL CHEMISTRY

Recent Advances in the Development of Acetyl-CoA Carboxylase (ACC) Inhibitors for the Treatment of Metabolic Disease

(2014) Matthew P. Bourbeau et al.   JOURNAL OF MEDICINAL CHEMISTRY

Synthesis and Biological Evaluation of Paleo-Soraphens

(2013) Hai-Hua Lu et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Cellular Fatty Acid Metabolism and Cancer

(2013) Erin Currie et al.   Cell Metabolism

Piperazine Oxadiazole Inhibitors of Acetyl-CoA Carboxylase

(2013) Matthew P. Bourbeau et al.   JOURNAL OF MEDICINAL CHEMISTRY

Spirolactam-Based Acetyl-CoA Carboxylase Inhibitors: Toward Improved Metabolic Stability of a Chromanone Lead Structure

(2013) David A. Griffith et al.   JOURNAL OF MEDICINAL CHEMISTRY

Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: a pooled analysis of 97 prospective cohorts with 1·8 million participants

(2013)   LANCET

Synthesis of C11-Desmethoxy Soraphen A1α: A Natural Product Analogue That Inhibits Acetyl-CoA Carboxylase

(2013) Daniel P. Canterbury et al.   ACS Medicinal Chemistry Letters

Design, synthesis, and structure–activity relationships of novel spiro-piperidines as acetyl-CoA carboxylase inhibitors

(2012) Makoto Kamata et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Symmetrical approach of spiro-pyrazolidinediones as acetyl-CoA carboxylase inhibitors

(2012) Makoto Kamata et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Synthesis of 7-Oxo-dihydrospiro[indazole-5,4′-piperidine] Acetyl-CoA Carboxylase Inhibitors

(2012) Scott W. Bagley et al.   JOURNAL OF ORGANIC CHEMISTRY

Synthesis of Spiropiperidine Lactam Acetyl-CoA Carboxylase Inhibitors

(2012) Kim Huard et al.   JOURNAL OF ORGANIC CHEMISTRY

Design of small molecule inhibitors of acetyl-CoA carboxylase 1 and 2 showing reduction of hepatic malonyl-CoA levels in vivo in obese Zucker rats

(2011) Christoffer Bengtsson et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Discovery of novel (4-piperidinyl)-piperazines as potent and orally active acetyl-CoA carboxylase 1/2 non-selective inhibitors: F-Boc and triF-Boc groups are acid-stable bioisosteres for the Boc group

(2011) Tomomichi Chonan et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Design, synthesis, and structure–activity relationships of spirolactones bearing 2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors

(2011) Tohru Yamashita et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Stimulation of Fat Oxidation, but no Sustained Reduction of Hepatic Lipids by Prolonged Pharmacological Inhibition of Acetyl CoA Carboxylase

(2011) M. Glien et al.   HORMONE AND METABOLIC RESEARCH

Maximizing Lipophilic Efficiency: The Use of Free-Wilson Analysis in the Design of Inhibitors of Acetyl-CoA Carboxylase

(2011) Kevin D. Freeman-Cook et al.   JOURNAL OF MEDICINAL CHEMISTRY

Soraphen A, an inhibitor of acetyl CoA carboxylase activity, interferes with fatty acid elongation

(2010) Donald B. Jump et al.   BIOCHEMICAL PHARMACOLOGY

Design and synthesis of disubstituted (4-piperidinyl)-piperazine derivatives as potent acetyl-CoA carboxylase inhibitors

(2010) Tomomichi Chonan et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

De novo Lipogenesis Protects Cancer Cells from Free Radicals and Chemotherapeutics by Promoting Membrane Lipid Saturation

(2010) E. Rysman et al.   CANCER RESEARCH

Identification and Synthesis of Novel Inhibitors of Acetyl-CoA Carboxylase with in Vitro and in Vivo Efficacy on Fat Oxidation

(2010) Stefanie Keil et al.   JOURNAL OF MEDICINAL CHEMISTRY

Mechanism for the inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase by pinoxaden

(2010) L. P. C. Yu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Asymmetric Total Synthesis of Soraphen A: A Flexible Alkyne Strategy

(2009) Barry M. Trost et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK

(2009) Yong Soon Cho et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Characterization of recombinant human acetyl-CoA carboxylase-2 steady-state kinetics

(2009) Virendar K. Kaushik et al.   BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS

(4-Piperidinyl)-piperazine: A new platform for acetyl-CoA carboxylase inhibitors

(2009) Tomomichi Chonan et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of small molecule isozyme non-specific inhibitors of mammalian acetyl-CoA carboxylase 1 and 2

(2009) Jeffrey W. Corbett et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The farnesoid X receptor (FXR) as a new target in non-alcoholic steatohepatitis

(2009) B. Cariou   DIABETES & METABOLISM

Soraphen, an inhibitor of the acetyl-CoA carboxylase system, improves peripheral insulin sensitivity in mice fed a high-fat diet

(2009) M. Schreurs et al.   DIABETES OBESITY & METABOLISM

aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues

(2009) J. Mao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A different mechanism for the inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase by tepraloxydim

(2009) S. Xiang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Malonyl-CoA, a Key Signaling Molecule in Mammalian Cells

(2008) David Saggerson   Annual Review of Nutrition

Control of Cell Growth and Survival by Enzymes of the Fatty Acid Synthesis Pathway in HCT-116 Colon Cancer Cells

(2008) Y. Zhan et al.   CLINICAL CANCER RESEARCH

Chronic Suppression of Acetyl-CoA Carboxylase 1 in β-Cells Impairs Insulin Secretion via Inhibition of Glucose Rather Than Lipid Metabolism

(2008) Sarah M. Ronnebaum et al.   JOURNAL OF BIOLOGICAL CHEMISTRY