A novel Lipoprotein lipase (LPL) agonist rescues the enzyme from inhibition by angiopoietin-like 4 (ANGPTL4).
Lipoprotein lipase (LPL) is a key physiological regulator of triglycerides and atherosclerosis risk. Random screening identified a compound designated C10, showing greater LPL agonist activity than NO-1886, a known LPL agonist. Structure-activity relationship (SAR) exploration of C10 led to the identification of C10d exhibiting at least two fold greater LPL activation than NO-1886. Unlike NO-1886, novel LPL agonists C10 and C10d reversed the LPL inhibition by angiopoietin-like 4 (ANGPTL4), a physiological inhibitor of LPL.
Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, USA.
Werner J
WJ
Geldenhuys
Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, USA.
Danielle
D
Aring
Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272, USA. Electronic address: psadana@neomed.edu.
Prabodh
P
Sadana
D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism*; D001549:Benzamides / Q000494:pharmacology; D055808:Drug Discovery; D004789:Enzyme Activation / Q000187:drug effects*; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D062105:Molecular Docking Simulation; D009943:Organophosphorus Compounds / Q000494:pharmacology
C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D001549:Benzamides; D009943:Organophosphorus Compounds; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D008071:Lipoprotein Lipase
ANGPTL4; Atherosclerosis; High-throughput screen; Homology model; Ibrolipim; LPL; NO-1886