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:C0022104 (
irritable bowel syndrome
)
8,033
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Matrix metalloproteinases (MMPs) play important roles in cancer progression and, despite their inhibitors have failed in the clinical trials, they have always been considered as suitable targets for the treatment of tumor. We have recently shown that membrane type (MT) 2-MMPs, is selectively expressed in multiple myeloma (MM) cells and mediates the metastatic characteristics of these cells. In this study, we designed efficient inhibitors against
MT2-MMP
using state-of-art molecular modeling methods. First, the 3D structure of
MT2-MMP
was predicted. Then, the proposed potent inhibitors against two regions of the catalytic domain of
MT2-MMP
(active site and MT-LOOP) were identified through molecular docking, QM-MM and molecular dynamics simulations from a set of compounds in Analyticon library,
IBS
library, Maybridge screening fragment library and drugbank library. Moreover, ADME estimation showed that pharmacokinetic properties of inhibitors are in the acceptable range for humans. Finally, our data suggested that compounds 'structures.722' (dobutamine) and 'M2' are suitable candidates to inhibit
MT2-MMP
for further examination in the laboratory.Communicated by Ramaswamy H. Sarma.
...
PMID:Designing new generation of potent inhibitors against membrane-type matrix metalloproteinase-2: a computational effort against multiple myeloma. 3155 Oct 25
