Human protein tyrosine phosphatase 1B inhibitors: QSAR by genetic function approximation.
Protein tyrosine phosphatase 1B (PTP 1B), a negative regulator of insulin receptor signaling system, has emerged as a highly validated, attractive target for the treatment of non-insulin dependent diabetes mellitus (NIDDM) and obesity. As a result there is a growing interest in the development of potent and specific inhibitors for this enzyme. This quantitative structure-activity relationship (QSAR) study for a series of formylchromone derivatives as PTP lB inhibitors was performed using genetic function approximation (GFA) technique. The QSAR models were developed using a training set of 29 compounds and the predictive ability of the QSAR model was evaluated against a test set of 7 compounds. The internal and external consistency of the final QSAR model was 0.766 and 0.785. The statistical quality of QSAR models was assessed by statistical parameters r2, r2 (crossvalidated r2), r2pred (predictive r2) and lack of fit (LOF) measure. The results indicate that PTP lB inhibitory activity of the formylchromone derivatives is strongly dependent on electronic, thermodynamic and shape related parameters.
Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune-411038, India.
Narsingh
N
Sachan
Shivajirao S
SS
Kadam
Vithal M
VM
Kulkarni
D002626:Chemistry, Pharmaceutical / Q000706:statistics & numerical data; D002867:Chromones / Q000737:chemistry / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008956:Models, Chemical; D008958:Models, Molecular; D009765:Obesity / Q000188:drug therapy / Q000201:enzymology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D021281:Quantitative Structure-Activity Relationship
D002867:Chromones; D004791:Enzyme Inhibitors; C502480:formylchromone; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases