Abel Suárez – Castroa, Luis Chacón – Garcíaa, Andreas Bender and Claudia Araceli Contreras-Celedón
Molecular Design Laboratory, Institute of Chemical Biology, University City, Morelia, Michoacan, Mexico
Introduction: The kinase PDK1 plays a key role in the saignaling phatways of the insulin1 in where this kinae could be studied as a target on the design of novel compounds against diabetes mellitus2, the main goal in this research was to find new compounds as modulators of PDK1 different from the known ones.
Methods: The Zinc database with around 2 million of compounds was used filtering by PAINs. The virtual screening was carry out with molecular docking and pharmacophore structure based approaches using the 3HRF PDB code. The results were validated using Bayes theorem and ROC curves with decoys. A clustering analysis by K-means was done using extended connectivity fingerprints with the compound hits, then their activities were predicted with a QSAR study using compounds with known activity3 toward the PDK1.
Results: Two compunds were obtained with codes ZINC1908976 and ZINC3848332, their predicted activities (pAC50) toward PDK1 were 7.6 and 6.4 respectively compared with the reference compound 7Z that it has a pAC50 of 5.5, they showed best predicted activity.
Conclusions: Two low molecular weight compounds were found with better activity than the known activators of PDK1 as establishing new candidates proposed for the treatment of diabetes mellitus.
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