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Discovery of novel high potent and cellular active ADC type PTP1B inhibitors with selectivity over TC-PTP via modification interacting with C site
- Source :
- European Journal of Medicinal Chemistry. 144:692-700
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- PTP1B serving as a key negative regulator of insulin signaling is a novel target for type 2 diabetes and obesity. Modification at ring B of N-{4-[(3-Phenyl-ureido)-methyl]-phenyl}-methane-sulfonamide template to interact with residues Arg47 and Lys41 in the C site of PTP1B by molecular docking aided design resulted in the discovery of a series of novel high potent and selective inhibitors of PTP1B. The structure activity relationship interacting with the C site of PTP1B was well illustrated. Compounds 8 and 18 were shown to be the high potent and most promising PTP1B inhibitors with cellular activity and great selectivity over the highly homologous TCPTP and other PTPs.
- Subjects :
- 0301 basic medicine
Cellular activity
Stereochemistry
Negative regulator
Structure-Activity Relationship
03 medical and health sciences
0302 clinical medicine
Drug Discovery
Humans
Structure–activity relationship
Enzyme Inhibitors
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Pharmacology
Protein Tyrosine Phosphatase, Non-Receptor Type 2
Dose-Response Relationship, Drug
Molecular Structure
biology
Chemistry
Organic Chemistry
General Medicine
Molecular Docking Simulation
Insulin receptor
030104 developmental biology
030220 oncology & carcinogenesis
biology.protein
Selectivity
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 02235234
- Volume :
- 144
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....c9435ae18335470097c7ce103e1edf9a