Vildagliptin (LAF-237)

Names

[ Name ]:
Vildagliptin (LAF-237)

[Synonym ]:
2-Pyrrolidinecarbonitrile, 1-[2-[(3-hydroxytricyclo[3.3.1.1]dec-1-yl)amino]acetyl]-, (2S)-
Galvus
(-)-(2S)-1-[[(3-Hydroxytricyclo[3.3.1.1[3,7]]dec-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile
Vildagliptin
Laf 237
(2S)-1-[N-(3-Hydroxyadamantan-1-yl)glycyl]pyrrolidine-2-carbonitrile
(2S)-1-[N-(3-hydroxytricyclo[3.3.1.1]dec-1-yl)glycyl]pyrrolidine-2-carbonitrile
Unii-I6B4B2U96p
(2S)-1-[N-(3-Hydroxyadamantan-1-yl)glycyl]-2-pyrrolidinecarbonitrile

Biological Activity

[Description]:

Vildagliptin (LAF-237; NVP-LAF 237) inhibits DPP-4 with IC50 of 2.3 nM.IC50 Value: 2.3 nM[1]Target: DPP-4in vitro: Vildagliptin is an N-substituted glycyl-2-cyanopyrrolidine (figure 2). It is a potent competitive and reversible inhibitor of human and rodent DPP-4 in vitro, with a median inhibitory concentration (IC50) ~2-3 nmol/L. Importantly, vildagliptin inhibits DPP-4 with high specificity relative to other similar peptidases where its IC50 exceeds 200 mol/L [1].in vivo: Compared to age-, gender-, BMI-matched subjects with normal renal function, the mean AUC of vildagliptin after 14 days in patients with mild, moderate, and severe RI increased by 40%, 71%, and 100%, respectively [2]. The treatment was effective in modulating stress in pancreatic tissue, both by reducing levels of stress markers as well as by increasing activity of SOD and catalase. After analyzing the pancreatic histology, we found that vildagliptin was also able to preserve islets and pancreatic β-cells, especially at the concentration of 5 mg/kg [3].Clinical trial: FDA approved drug.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Dipeptidyl Peptidase

Research Areas >> Metabolic Disease

[References]

[1]. Villhauer EB, Brinkman JA, Naderi GB et al. 1-[[(3-hydroxy-1-adamantyl) amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem 2003;46:2774-89.

[2]. He YL, Kulmatycki K, Zhang Y, Pharmacokinetics of vildagliptin in patients with varying degrees of renal impairment. Int J Clin Pharmacol Ther. 2013 Jun 19.

[3]. Avila Dde L, Araújo GR, Silva M, Vildagliptin ameliorates oxidative stress and pancreatic beta cell destruction in type 1 diabetic rats. Arch Med Res. 2013 Apr;44(3):194-202.

[4]. Qin CJ, et al. Inhibition of dipeptidyl peptidase IV prevents high fat diet-induced liver cancer angiogenesis by downregulating chemokine ligand 2. Cancer Lett. 2018 Jan 31;420:26-37.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.27 g/cm3

[ Boiling Point ]:
531.3ºC at 760 mmHg

[ Melting Point ]:
153-155?C

[ Molecular Formula ]:
C₁₇H₂₅N₃O₂

[ Molecular Weight ]:
303.39900

[ Flash Point ]:
275.1ºC

[ Exact Mass ]:
303.19500

[ PSA ]:
76.36000

[ LogP ]:
1.50308

[ Storage condition ]:
-20°C Freezer

Safety Information

[ Hazard Codes ]:
Xi

[ HS Code ]:
2933990090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%