3-[2-((2S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramide analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes

Coumar, Mohane Selvaraj; Chang, Chung-Nien; Chen, Chiung‐Tong; Chen, Xin; Chien, Chia‐Hui; Tsai, Tsung‐Yen; Cheng, Jai-Hong; Wu, Hsin‐Yi; Han, Chia-Hung; Wu, Ssu-Hui; Huang, Yu-Wen; Hsu, Tsu; Hsu, Li-Jen; Chao, Yu‐Sheng; Hsieh, Hsing‐Pang; Jiaang, Weir‐Torn

doi:10.1016/j.bmcl.2006.12.019

Cited by 11 publications

(4 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Covalent and noncovalent inhibitors of DPP IV have been designed, developed, and evaluated in vitro, in vivo, and in clinical trials. Several synthetic routes were explored during these initial developments, − which will not be described in depth in this Perspective. We and many others have recently reviewed these initial developments. ,,, Thus, only the most relevant information, and in particular the information concerning the molecules that were evaluated in humans, will be provided here.…”

Section: Initial Development Of Dpp IV Inhibitors In Clinical Use For...mentioning

confidence: 99%

Dipeptidyl Peptidase IV and Its Inhibitors: Therapeutics for Type 2 Diabetes and What Else?

2013

View full text Add to dashboard Cite

The proline-specific dipeptidyl aminopeptidase IV (DPP IV, DPP-4, CD26), widely expressed in mammalians, releases X-Pro/Ala dipeptides from the N-terminus of peptides. DPP IV is responsible of the degradation of the incretin peptide hormones regulating blood glucose levels. Several families of DPP IV inhibitors have been synthesized and evaluated. Their positive effects on the degradation of the incretins and the control of blood glucose levels have been demonstrated in biological models and in clinical trials. Presently, several DPP IV inhibitors, the "gliptins", are approved for type 2 diabetes or are under clinical evaluation. However, the gliptins may also be of therapeutic interest for other diseases beyond the inhibition of incretin degradation. In this Perspective, the biological functions and potential substrates of DPP IV enzymes are reviewed and the characteristics of the DPP IV inhibitors are discussed in view of type 2 diabetes and further therapeutic interest.

show abstract

Section: Initial Development Of Dpp IV Inhibitors In Clinical Use For...mentioning

confidence: 99%

Dipeptidyl Peptidase IV and Its Inhibitors: Therapeutics for Type 2 Diabetes and What Else?

2013

View full text Add to dashboard Cite

show abstract

“…Vildagliptin is an anti-diabetic drug that covalently binds to the active site of DPP4 26 . The drug also inhibits other DPP4-related enzymes, such as FAP, DPP8 and DPP9 27 28 29 . We reasoned that, if the drug inhibits the peptidase activity of fly DPP10, the drug should then covalently modify the catalytic site of fly DPP10.…”

Section: Resultsmentioning

confidence: 99%

Fly DPP10 acts as a channel ancillary subunit and possesses peptidase activity

Shiina

Muto

Baihaqie

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Mammalian DPP6 (DPPX) and DPP10 (DPPY) belong to a family of dipeptidyl peptidases, but lack enzyme activity. Instead, these proteins form complexes with voltage-gated K+ channels in Kv4 family to control their gating and other properties. Here, we find that the fly DPP10 ortholog acts as an ancillary subunit of Kv4 channels and digests peptides. Similarly to mammalian DPP10, the fly ortholog tightly binds to rat Kv4.3 protein. The association causes negative shifts in voltage dependence of channel activation and steady state inactivation. It also results in faster inactivation and recovery from inactivation. In addition to its channel regulatory role, fly DPP10 exhibits significant dipeptidyl peptidase activity with Gly-Pro-MCA (glycyl-L-proline 4-methylcoumaryl-7-amide) as a substrate. Heterologously expressed Flag-tagged fly DPP10 and human DPP4 show similar Km values towards this substrate. However, fly DPP10 exhibits approximately a 6-times-lower relative kcat value normalized with anti-Flag immunoreactivity than human DPP4. These results demonstrate that fly DPP10 is a dual functional protein, controlling Kv4 channel gating and removing bioactive peptides.

show abstract

“…Three series of DPP-4 inhibitors have been synthesized using a linker for substituted anilines, benzylamines, and phenylethylamines to (2S)-cyanopyrrolidine; more than 20 compounds were thus evaluated (Coumar et al, 2007).…”

Section: E Other Compoundsmentioning

confidence: 99%

Novel Pharmacological Approaches to the Treatment of Type 2 Diabetes

Verspohl

2012

Pharmacol Rev

View full text Add to dashboard Cite

3-[2-((2S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramide analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes

Cited by 11 publications

References 20 publications

Dipeptidyl Peptidase IV and Its Inhibitors: Therapeutics for Type 2 Diabetes and What Else?

Dipeptidyl Peptidase IV and Its Inhibitors: Therapeutics for Type 2 Diabetes and What Else?

Fly DPP10 acts as a channel ancillary subunit and possesses peptidase activity

Novel Pharmacological Approaches to the Treatment of Type 2 Diabetes

Contact Info

Product

Resources

About