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Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors. 2007
Gang Liu, and
John K Lynch, and
Jennifer Freeman, and
Bo Liu, and
Zhili Xin, and
Hongyu Zhao, and
Michael D Serby, and
Philip R Kym, and
Tom S Suhar, and
Harriet T Smith, and
Ning Cao, and
Ruojing Yang, and
Rich S Janis, and
Joel A Krauser, and
Steven P Cepa, and
David W A Beno, and
Hing L Sham, and
Christine A Collins, and
Teresa K Surowy, and
Heidi S Camp
Metabolic Disease Research, Drug Metabolism, Advanced Technology, Exploratory Pharmacokinetics, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064-6101, USA. liugx@gmail.com
Stearoyl-CoA desaturase 1 (SCD1) catalyzes the committed step in the biosynthesis of monounsaturated fatty acids from saturated, long-chain fatty acids. Studies with SCD1 knockout mice have established that these animals are lean and protected from leptin deficiency-induced and diet-induced obesity, with greater whole body insulin sensitivity than wild-type animals. In this work, we have discovered a series of potent, selective, orally bioavailable SCD1 inhibitors based on a known pyridazine carboxamide template. The representative lead inhibitor 28c also demonstrates excellent cellular activity in blocking the conversion of saturated long-chain fatty acid-CoAs (LCFA-CoAs) to monounsaturated LCFA-CoAs in HepG2 cells.
Related Publications
Gang Liu, and
John K Lynch, and
Jennifer Freeman, and
Bo Liu, and
Zhili Xin, and
Hongyu Zhao, and
Michael D Serby, and
Philip R Kym, and
Tom S Suhar, and
Harriet T Smith, and
Ning Cao, and
Ruojing Yang, and
Rich S Janis, and
Joel A Krauser, and
Steven P Cepa, and
David W A Beno, and
Hing L Sham, and
Christine A Collins, and
Teresa K Surowy, and
Heidi S Camp
August 2009,
Bioorganic & medicinal chemistry letters,
Gang Liu, and
John K Lynch, and
Jennifer Freeman, and
Bo Liu, and
Zhili Xin, and
Hongyu Zhao, and
Michael D Serby, and
Philip R Kym, and
Tom S Suhar, and
Harriet T Smith, and
Ning Cao, and
Ruojing Yang, and
Rich S Janis, and
Joel A Krauser, and
Steven P Cepa, and
David W A Beno, and
Hing L Sham, and
Christine A Collins, and
Teresa K Surowy, and
Heidi S Camp
June 2009,
Bioorganic & medicinal chemistry letters,
Gang Liu, and
John K Lynch, and
Jennifer Freeman, and
Bo Liu, and
Zhili Xin, and
Hongyu Zhao, and
Michael D Serby, and
Philip R Kym, and
Tom S Suhar, and
Harriet T Smith, and
Ning Cao, and
Ruojing Yang, and
Rich S Janis, and
Joel A Krauser, and
Steven P Cepa, and
David W A Beno, and
Hing L Sham, and
Christine A Collins, and
Teresa K Surowy, and
Heidi S Camp
December 2013,
Bioorganic & medicinal chemistry letters,
Gang Liu, and
John K Lynch, and
Jennifer Freeman, and
Bo Liu, and
Zhili Xin, and
Hongyu Zhao, and
Michael D Serby, and
Philip R Kym, and
Tom S Suhar, and
Harriet T Smith, and
Ning Cao, and
Ruojing Yang, and
Rich S Janis, and
Joel A Krauser, and
Steven P Cepa, and
David W A Beno, and
Hing L Sham, and
Christine A Collins, and
Teresa K Surowy, and
Heidi S Camp
February 2015,
Bioorganic & medicinal chemistry,
Gang Liu, and
John K Lynch, and
Jennifer Freeman, and
Bo Liu, and
Zhili Xin, and
Hongyu Zhao, and
Michael D Serby, and
Philip R Kym, and
Tom S Suhar, and
Harriet T Smith, and
Ning Cao, and
Ruojing Yang, and
Rich S Janis, and
Joel A Krauser, and
Steven P Cepa, and
David W A Beno, and
Hing L Sham, and
Christine A Collins, and
Teresa K Surowy, and
Heidi S Camp
March 2014,
Bioorganic & medicinal chemistry letters,
Gang Liu, and
John K Lynch, and
Jennifer Freeman, and
Bo Liu, and
Zhili Xin, and
Hongyu Zhao, and
Michael D Serby, and
Philip R Kym, and
Tom S Suhar, and
Harriet T Smith, and
Ning Cao, and
Ruojing Yang, and
Rich S Janis, and
Joel A Krauser, and
Steven P Cepa, and
David W A Beno, and
Hing L Sham, and
Christine A Collins, and
Teresa K Surowy, and
Heidi S Camp
April 2009,
Bioorganic & medicinal chemistry letters,
Gang Liu, and
John K Lynch, and
Jennifer Freeman, and
Bo Liu, and
Zhili Xin, and
Hongyu Zhao, and
Michael D Serby, and
Philip R Kym, and
Tom S Suhar, and
Harriet T Smith, and
Ning Cao, and
Ruojing Yang, and
Rich S Janis, and
Joel A Krauser, and
Steven P Cepa, and
David W A Beno, and
Hing L Sham, and
Christine A Collins, and
Teresa K Surowy, and
Heidi S Camp
January 2012,
Bioorganic & medicinal chemistry letters,
Gang Liu, and
John K Lynch, and
Jennifer Freeman, and
Bo Liu, and
Zhili Xin, and
Hongyu Zhao, and
Michael D Serby, and
Philip R Kym, and
Tom S Suhar, and
Harriet T Smith, and
Ning Cao, and
Ruojing Yang, and
Rich S Janis, and
Joel A Krauser, and
Steven P Cepa, and
David W A Beno, and
Hing L Sham, and
Christine A Collins, and
Teresa K Surowy, and
Heidi S Camp
August 2008,
Bioorganic & medicinal chemistry letters,
Gang Liu, and
John K Lynch, and
Jennifer Freeman, and
Bo Liu, and
Zhili Xin, and
Hongyu Zhao, and
Michael D Serby, and
Philip R Kym, and
Tom S Suhar, and
Harriet T Smith, and
Ning Cao, and
Ruojing Yang, and
Rich S Janis, and
Joel A Krauser, and
Steven P Cepa, and
David W A Beno, and
Hing L Sham, and
Christine A Collins, and
Teresa K Surowy, and
Heidi S Camp
January 2013,
Journal of medicinal chemistry,
Gang Liu, and
John K Lynch, and
Jennifer Freeman, and
Bo Liu, and
Zhili Xin, and
Hongyu Zhao, and
Michael D Serby, and
Philip R Kym, and
Tom S Suhar, and
Harriet T Smith, and
Ning Cao, and
Ruojing Yang, and
Rich S Janis, and
Joel A Krauser, and
Steven P Cepa, and
David W A Beno, and
Hing L Sham, and
Christine A Collins, and
Teresa K Surowy, and
Heidi S Camp
June 2007,
Bioorganic & medicinal chemistry letters,
