nateglinide   

GtoPdb Ligand ID: 6833

Synonyms: AY-4166 | SDZ-DJN-608 | Starlix®
nateglinide is an approved drug (FDA (2000), EMA (2001))
Compound class: Synthetic organic
Comment: A sulfonylurea receptor 1, Kir6.2 blocker, but belonging to the metiglinides drug family. Note that the PubChem CID listed here is a slightly different isomer to the ChEMBL ligand and the INN structure.
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2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 66.4
Molecular weight 317.2
XLogP 4.56
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES CC(C1CCC(CC1)C(=O)NC(C(=O)O)Cc1ccccc1)C
Isomeric SMILES CC([C@@H]1CC[C@H](CC1)C(=O)N[C@@H](C(=O)O)Cc1ccccc1)C
InChI InChI=1S/C19H27NO3/c1-13(2)15-8-10-16(11-9-15)18(21)20-17(19(22)23)12-14-6-4-3-5-7-14/h3-7,13,15-17H,8-12H2,1-2H3,(H,20,21)(H,22,23)/t15-,16-,17-/m1/s1
InChI Key OELFLUMRDSZNSF-BRWVUGGUSA-N
References
1. Anderson CM, Jevons M, Thangaraju M, Edwards N, Conlon NJ, Woods S, Ganapathy V, Thwaites DT. (2010)
Transport of the photodynamic therapy agent 5-aminolevulinic acid by distinct H+-coupled nutrient carriers coexpressed in the small intestine.
J. Pharmacol. Exp. Ther., 332 (1): 220-8. [PMID:19789362]
2. Balimane P, Sinko P. (2000)
Effect of ionization on the variable uptake of valacyclovir via the human intestinal peptide transporter (hPepT1) in CHO cells.
Biopharm Drug Dispos, 21 (5): 165-74. [PMID:11180195]
3. Balimane PV, Tamai I, Guo A, Nakanishi T, Kitada H, Leibach FH, Tsuji A, Sinko PJ. (1998)
Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir.
Biochem. Biophys. Res. Commun., 250 (2): 246-51. [PMID:9753615]
4. Bhardwaj RK, Herrera-Ruiz D, Sinko PJ, Gudmundsson OS, Knipp G. (2005)
Delineation of human peptide transporter 1 (hPepT1)-mediated uptake and transport of substrates with varying transporter affinities utilizing stably transfected hPepT1/Madin-Darby canine kidney clones and Caco-2 cells.
J. Pharmacol. Exp. Ther., 314 (3): 1093-100. [PMID:15901802]
5. Darcel NP, Liou AP, Tomé D, Raybould HE. (2005)
Activation of vagal afferents in the rat duodenum by protein digests requires PepT1.
J. Nutr., 135 (6): 1491-5. [PMID:15930458]
6. Döring F, Walter J, Will J, Föcking M, Boll M, Amasheh S, Clauss W, Daniel H. (1998)
Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications.
J. Clin. Invest., 101 (12): 2761-7. [PMID:9637710]
7. Ganapathy ME, Brandsch M, Prasad PD, Ganapathy V, Leibach FH. (1995)
Differential recognition of beta -lactam antibiotics by intestinal and renal peptide transporters, PEPT 1 and PEPT 2.
J. Biol. Chem., 270 (43): 25672-7. [PMID:7592745]
8. Guo A, Hu P, Balimane PV, Leibach FH, Sinko PJ. (1999)
Interactions of a nonpeptidic drug, valacyclovir, with the human intestinal peptide transporter (hPEPT1) expressed in a mammalian cell line.
J. Pharmacol. Exp. Ther., 289 (1): 448-54. [PMID:10087037]
9. Herrera-Ruiz D, Faria TN, Bhardwaj RK, Timoszyk J, Gudmundsson OS, Moench P, Wall DA, Smith RL, Knipp GT. (2004)
A novel hPepT1 stably transfected cell line: establishing a correlation between expression and function.
Mol. Pharm., 1 (2): 136-44. [PMID:15832510]
10. Irie M, Terada T, Sawada K, Saito H, Inui K. (2001)
Recognition and transport characteristics of nonpeptidic compounds by basolateral peptide transporter in Caco-2 cells.
J. Pharmacol. Exp. Ther., 298 (2): 711-7. [PMID:11454935]
11. Knütter I, Hartrodt B, Theis S, Foltz M, Rastetter M, Daniel H, Neubert K, Brandsch M. (2004)
Analysis of the transport properties of side chain modified dipeptides at the mammalian peptide transporter PEPT1.
Eur J Pharm Sci, 21 (1): 61-7. [PMID:14706812]
12. Knütter I, Theis S, Hartrodt B, Born I, Brandsch M, Daniel H, Neubert K. (2001)
A novel inhibitor of the mammalian peptide transporter PEPT1.
Biochemistry, 40 (14): 4454-8. [PMID:11284702]
13. Meredith D, Boyd CA, Bronk JR, Bailey PD, Morgan KM, Collier ID, Temple CS. (1998)
4-aminomethylbenzoic acid is a non-translocated competitive inhibitor of the epithelial peptide transporter PepT1.
J. Physiol. (Lond.), 512 ( Pt 3): 629-34. [PMID:9882198]
14. Neumann J, Brandsch M. (2003)
Delta-aminolevulinic acid transport in cancer cells of the human extrahepatic biliary duct.
J. Pharmacol. Exp. Ther., 305 (1): 219-24. [PMID:12649372]
15. Ocheltree SM, Shen H, Hu Y, Xiang J, Keep RF, Smith DE. (2004)
Mechanisms of cefadroxil uptake in the choroid plexus: studies in wild-type and PEPT2 knockout mice.
J. Pharmacol. Exp. Ther., 308 (2): 462-7. [PMID:14600253]
16. Rodriguez L, Batlle A, Di Venosa G, MacRobert AJ, Battah S, Daniel H, Casas A. (2006)
Study of the mechanisms of uptake of 5-aminolevulinic acid derivatives by PEPT1 and PEPT2 transporters as a tool to improve photodynamic therapy of tumours.
Int. J. Biochem. Cell Biol., 38 (9): 1530-9. [PMID:16632403]
17. Sawada K, Terada T, Saito H, Hashimoto Y, Inui K. (1999)
Effects of glibenclamide on glycylsarcosine transport by the rat peptide transporters PEPT1 and PEPT2.
Br. J. Pharmacol., 128 (6): 1159-64. [PMID:10578127]
18. Terada T, Sawada K, Saito H, Hashimoto Y, Inui K. (2000)
Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2.
Eur. J. Pharmacol., 392 (1-2): 11-7. [PMID:10748266]
19. Theis S, Hartrodt B, Kottra G, Neubert K, Daniel H. (2002)
Defining minimal structural features in substrates of the H(+)/peptide cotransporter PEPT2 using novel amino acid and dipeptide derivatives.
Mol. Pharmacol., 61 (1): 214-21. [PMID:11752223]
20. Wenzel U, Gebert I, Weintraut H, Weber WM, Clauss W, Daniel H. (1996)
Transport characteristics of differently charged cephalosporin antibiotics in oocytes expressing the cloned intestinal peptide transporter PepT1 and in human intestinal Caco-2 cells.
J. Pharmacol. Exp. Ther., 277 (2): 831-9. [PMID:8627565]
21. Xiang J, Hu Y, Smith DE, Keep RF. (2006)
PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes.
Brain Res., 1122 (1): 18-23. [PMID:17034769]