NDLI: Potency and pharmacokinetics of broad spectrum and isoform-specific p110Î³ and Î´ inhibitors in cancers.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Setti, Aravind Kumar, M. J. Vijay Babu, K. Ravi Rasagna, A. Prasanna, M. G. R. Devi Devi, T. A. Phazna Pawar, Smita C.
Description	Country affiliation: India Author Affiliation: Setti A ( a Department of Genetics & Biotechnology , Osmania University , Hyderabad , Andhra Pradesh , India .); Kumar MJ ( b Param Bioinformatics , Hyderabad , Andhra Pradesh , India .); Babu KR ( c VAC Biotechnologies , Hyderabad , Andhra Pradesh , India .); Rasagna A ( a Department of Genetics & Biotechnology , Osmania University , Hyderabad , Andhra Pradesh , India .); Prasanna MG ( c VAC Biotechnologies , Hyderabad , Andhra Pradesh , India .); Devi TA ( d Department of Biochemistry , Indian Institute of Science , Bangalore , Karnataka , India , and.); Pawar SC ( a Department of Genetics & Biotechnology , Osmania University , Hyderabad , Andhra Pradesh , India .)
Abstract	Emerging data on cancer suggesting that target-based therapy is promising strategy in cancer treatment. PI3K-AKT pathway is extensively studied in many cancers; several inhibitors target this pathway in different levels. Recent finding on this pathway uncovered the therapeutic applications of PI3K-specific inhibitors; PI3K, AKT, and mTORC broad spectrum inhibitors. Noticeably, class I PI3K isoforms, p110Î³ and p110Î´ catalytic subunits have rational therapeutic application than other isoforms. Therefore, three classes of inhibitors: isoform-specific, dual-specific and broad spectrum were selected for molecular docking and dynamics. First, p110Î´ structure was modelled; active site was analyzed. Then, molecular docking of each class of inhibitors were studied; the docked complexes were further used in 1.2 ns molecular dynamics simulation to report the potency of each class of inhibitor. Remarkably, both the studies retained the similar kind of protein ligand interactions. GDC-0941, XL-147 (broad spectrum); TG100-115 (dual-specific); and AS-252424, PIK-294 (isoform-specific) were found to be potential inhibitors of p110Î³ and p110Î´, respectively. In addition to that pharmacokinetic properties are within recommended ranges. Finally, molecular phylogeny revealed that p110Î³ and p110Î´ are evolutionarily divergent; they probably need separate strategies for drug development.
File Format	HTM / HTML
ISSN	10799893
Issue Number	1
Volume Number	36
e-ISSN	15324281
Journal	Journal of Receptors and Signal Transduction
Language	English
Publisher	Taylor & Francis
Publisher Date	2016-01-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Cell Biology Discipline Physiology Discipline Biochemistry Neoplasms Drug Therapy Phosphatidylinositol 3-kinases Antagonists & Inhibitors Protein Kinase Inhibitors Pharmacology Pharmacokinetics Amino Acid Sequence Humans Molecular Docking Simulation Molecular Sequence Data Enzymology Protein Isoforms Chemistry Protein Subunits Sequence Homology, Amino Acid Signal Transduction Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in