Details of the Drug

General Information of Drug (ID: DMYN59P)

Drug Name
Vildagliptin
Synonyms
Equa; Galvu; Galvus; Jalra; Xiliarx; Galvus (TN); Vidagliptin (see Vildagliptin); Vildagliptin (JAN/USAN/INN); (2S)-(((3-hydroxyadamantan-1-yl)amino)acetyl)pyrrolidine-2-carbonitrile; (2S)-1-[2-[(3-hydroxy-1-adamantyl)amino]acetyl]pyrrolidine-2-carbonitrile; 1-[2-[(3-hydroxy-1-adamantyl)amino]acetyl]pyrrolidine-2-carbonitrile; 2-Pyrrolidinecarbonitrile, 1-[[(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)amino]acetyl]-, (2S)-(9CI)
Indication
Disease Entry ICD 11 Status REF
Type-2 diabetes 5A11 Approved [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 303.4
Topological Polar Surface Area (xlogp) 0.9
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2-3 h [3]
Bioavailability
The bioavailability of drug is 60%-70% [3]
Clearance
The renal clearance of drug is 13 L/h [4]
Elimination
Following oral administration, approximately 85% of the radiolabelled vildagliptin dose was excreted in urine and about 15% of the dose was recovered in feces [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 3 hours [4]
Unbound Fraction
The unbound fraction of drug in plasma is 0.885123618% [5]
Vd
The volume of distribution (Vd) of drug is 71 L [4]
Chemical Identifiers
Formula
C17H25N3O2
IUPAC Name
(2S)-1-[2-[(3-hydroxy-1-adamantyl)amino]acetyl]pyrrolidine-2-carbonitrile
Canonical SMILES
C1C[C@H](N(C1)C(=O)CNC23CC4CC(C2)CC(C4)(C3)O)C#N
InChI
InChI=1S/C17H25N3O2/c18-9-14-2-1-3-20(14)15(21)10-19-16-5-12-4-13(6-16)8-17(22,7-12)11-16/h12-14,19,22H,1-8,10-11H2/t12?,13?,14-,16?,17?/m0/s1
InChIKey
SYOKIDBDQMKNDQ-XWTIBIIYSA-N
Cross-matching ID
PubChem CID
6918537
ChEBI ID
CHEBI:135285
CAS Number
274901-16-5
DrugBank ID
DB04876
TTD ID
D0L3DK
VARIDT ID
DR01409

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Dipeptidyl peptidase 4 (DPP-4) TTDIGC1 DPP4_HUMAN Inhibitor [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Type-2 diabetes
ICD Disease Classification 5A11
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Dipeptidyl peptidase 4 (DPP-4) DTT DPP4 9.54E-01 -0.27 -1.85
P-glycoprotein 1 (ABCB1) DTP P-GP 2.30E-01 3.06E-01 7.43E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6310).
2 Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes. Curr Drug Targets. 2009 Jan;10(1):71-87.
3 Cubeddu LX, Fuenmayor N, Caplan N, Ferry D: Clinical pharmacology of doxazosin in patients with essential hypertension. Clin Pharmacol Ther. 1987 Apr;41(4):439-49. doi: 10.1038/clpt.1987.54.
4 Summary of Product Characteristics: Galvus (vildagliptin) oral tablets
5 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6 Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58.
7 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
8 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
9 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
10 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
11 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
12 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
13 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
14 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
15 Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol Ther. 2009 Oct;124(1):113-38.
16 Clinical pipeline report, company report or official report of Takeda (2009).
17 Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
18 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
19 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1612).
20 Diabetes Treatment. Diabetes Care. 2009 March; 32(3): e25-e30.
21 Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for type 2 diabetes. Cardiol Rev. 2010 Jul-Aug;18(4):213-7.
22 Clinical pipeline report, company report or official report of ShangHai APIs Chemical.
23 Dutogliptin, a selective DPP4 inhibitor, improves glycaemic control in patients with type 2 diabetes: a 12-week, double-blind, randomized, placebo-controlled, multicentre trial. Diabetes Obes Metab. 2010 Apr;12(4):348-55.