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Suppressor of Cytokine Signalling‐3 as a Drug Target for Type 2 Diabetes Mellitus: A Structure‐Guided Approach
Author(s) -
Dumpati Ramakrishna,
Dulapalli Ramasree,
Kondagari Bhargavi,
Ramatenki Vishwanath,
Vellanki Santhiprada,
Vadija Rajender,
Vuruputuri Uma
Publication year - 2016
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201600640
Subject(s) - drug discovery , docking (animal) , in silico , drug , lipinski's rule of five , pharmacology , small molecule , computational biology , type 2 diabetes mellitus , chemistry , biology , diabetes mellitus , medicine , biochemistry , endocrinology , gene , nursing
The present study treats Suppressor of cytokine signalling 3 (SOCS‐3) as a novel target for type 2 diabetes mellitus (T2DM) drug discovery. An in silico 3D structural evaluation and validation of the SOCS‐3 and its cognate receptor, Insulin Receptor Beta (IR−B) was carried out. The active site of SOCS‐3 was identified using computational tools and Protein‐Protein docking with IR−B. The docking study with T2DM drugs and corroborating with the results of virtual screening using small molecules, ratify the residues of the catalytic site of SOCS‐3, i. e. Arg‐71 along with Asp‐72, Ser‐73, Ser‐74, and Asp‐92, to facilitate the binding. The T2DM drugs which belong to Sulfonylureas class show partial affinity towards SOCS‐3. The ligands show acceptable pharmacokinetic properties in terms of Lipinski's rule of 5, Jorgensen's rule of 3, brain/blood partition coefficient, binding to human serum albumin and skin permeability. The identified ligands show good predicted IC 50 values and hence can act as SOCS‐3 antagonists. The structural data of SOCS‐3 active site and the identified ligands are useful in development of new T2DM therapeutics.