Detailansicht
Design, Synthesis and Evaluation of Small Molecules as ALK5 Inhibitors
ISBN/EAN: 9783659479922
Umbreit-Nr.: 6061723
Sprache:
Englisch
Umfang: 52 S.
Format in cm: 0.4 x 22 x 15
Einband:
kartoniertes Buch
Erschienen am 04.12.2018
Auflage: 1/2018
- Zusatztext
- A new series of imidazo[2,1-b][1,3,4]thiadiazoles were synthesized as transforming growth factor- (TGF- ) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF- -induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. One of the compound from this series displayed prominent ALK5 inhibition (IC50 = 0.0012 µM) and elective inhibition (91%) against the P38 kinase at 10 µM. The binding mode of this compound by XP docking studies showed that it ts well into the active site cavity of ALK5 by forming broad and tight interactions. Lipinskis rule and in silico ADME pharmacokinetic parameters are within the acceptable range defined for human use, thereby indicating their potential as a drug-like molecules.
- Autorenportrait
- Dr. R. Karpoormath is professor at the faculty in the Dis. of Pharmaceutical Sciences, University of KwaZulu-Natal, Durban, South Africa. His research interests are: target based drug design (HIV, Cancer and TB), Methodology development and development of electroanalytical method to trace biological, organic species with modified electrodes.