TY - JOUR T1 - Pharmacophore Based Virtual Screening Approach to Identify Selective PDE4B Inhibitors. AU - Gaurav,Anand, AU - Gautam,Vertika, PY - 2017/12/5/entrez PY - 2017/12/5/pubmed PY - 2017/12/5/medline KW - HypoGen KW - Pharmacophore KW - Phosphodiesterase 4 KW - Virtual screening KW - Zinc database KW - docking SP - 910 EP - 923 JF - Iranian journal of pharmaceutical research : IJPR JO - Iran J Pharm Res VL - 16 IS - 3 N2 - Phosphodiesterase 4 (PDE4) has been established as a promising target in asthma and chronic obstructive pulmonary disease. PDE4B subtype selective inhibitors are known to reduce the dose limiting adverse effect associated with non-selective PDE4B inhibitors. This makes the development of PDE4B subtype selective inhibitors a desirable research goal. To achieve this goal, ligand based pharmacophore modeling approach is employed. Separate pharmacophore hypotheses for PDE4B and PDE4D inhibitors were generated using HypoGen algorithm and 106 PDE4 inhibitors from literature having thiopyrano [3,2-d] Pyrimidines, 2-arylpyrimidines, and triazines skeleton. Suitable training and test sets were created using the molecules as per the guidelines available for HypoGen program. Training set was used for hypothesis development while test set was used for validation purpose. Fisher validation was also used to test the significance of the developed hypothesis. The validated pharmacophore hypotheses for PDE4B and PDE4D inhibitors were used in sequential virtual screening of zinc database of drug like molecules to identify selective PDE4B inhibitors. The hits were screened for their estimated activity and fit value. The top hit was subjected to docking into the active sites of PDE4B and PDE4D to confirm its selectivity for PDE4B. The hits are proposed to be evaluated further using in-vitro assays. SN - 1735-0328 UR - https://www.unboundmedicine.com/medline/citation/29201082/Pharmacophore_Based_Virtual_Screening_Approach_to_Identify_Selective_PDE4B_Inhibitors_ DB - PRIME DP - Unbound Medicine ER -