A new screening method based on yeast-expressed human dipeptidyl peptidase IV and discovery of novel inhibitors.
Dipeptidyl peptidase (DPP) IV inhibitors provide a new strategy for the treatment of type 2 diabetes. Human DPP-IV gene was cloned from differentiated Caco-2 cells and expressed in Pichia pastoris. The recombinant enzyme was used in a new system for screening of DPP-IV inhibitors. By high throughput screening, a novel compound (W5188) was identified from 75,000 compounds with an IC(50) of 6.5 microM. This method is highly reproducible and reliable for discovery of DPP-IV inhibitors as shown by Z' value of 0.73 and S/N ratio of 6.89.
Hu
Chen-Xi
CX
Department of Biosynthesis of Natural Products, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100050, China. Suhappy99@sohu.com
Huang
Hui
H
Zhang
Li
L
Huang
You
Y
Shen
Zhu-Fang
ZF
Cheng
Ke-Di
KD
Du
Guan-Hua
GH
Zhu
Ping
P
D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis* / Q000235:genetics; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D010843:Pichia / Q000201:enzymology* / Q000235:genetics*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics
D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4