Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0220723 (
PCA
)
4,687
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Owing to its negative regulatory role in insulin signaling, protein tyrosine phosphatase of leukocyte antigen-related protein (PTP-LAR) was widely thought as a potential drug target for diabetes. Now, it was urgent to search for potential
LAR
inhibitors targeting diabetes. Initially, the pharmacophore models of
LAR
inhibitors were established with the application of the HypoGen module. The cost analysis, test set validation, as well as Fischer's test was used to verify the efficiency of pharmacophore model. Then, the best pharmacophore model (Hypo-1-LAR) was applied for the virtual screening of the ZINC database. And 30 compounds met the Lipinski's rule of five. Among them, 10 compounds with better binding affinity than the known
LAR
inhibitor (BDBM50296375) were discovered by docking studies. Finally, molecular dynamics simulations and post-analysis experiments (RMSD, RMSF,
PCA
, DCCM and RIN) were conducted to explore the effect of ligands (ZINC97018474 and Compound
1
) on
LAR
and preliminary understand why ZINC97018474 had better inhibitory activity than Compound
1
(BDBM50296375). Communicated by Ramaswamy H. Sarma.
...
PMID:Identification of potential leukocyte antigen-related protein (PTP-LAR) inhibitors through 3D QSAR pharmacophore-based virtual screening and molecular dynamics simulation. 3158 70
