Identification

Name
Sitagliptin
Accession Number
DB01261
Description

Sitagliptin is an oral dipeptidyl peptidase-4 (DPP-4) inhibitor used in conjunction with diet and exercise to improve glycemic control in patients with type 2 diabetes mellitusLabel,4,1,2. The effect of this medication leads to glucose dependent increases in insulin and decreases in glucagon to improve control of blood sugarLabel,1. Sitagliptin was granted FDA approval on October 16, 20066.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 407.3136
Monoisotopic: 407.118079357
Chemical Formula
C16H15F6N5O
Synonyms
  • Sitagliptin
  • Sitagliptina
  • Sitagliptine
  • Sitagliptinum
External IDs
  • LEZ-763
  • LEZ763

Pharmacology

Indication

Sitagliptin is indicated for the management of glycemic control in type 2 diabetes mellitus along with diet and exerciseLabel.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Sitagliptin inhibits DPP-4 which leads to increased levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide(GIP), decreased levels of glucagon, and a stronger insulin response to glucoseLabel,4,1,2.

Mechanism of action

Inhibition of DPP-4 by sitagliptin slows DPP-4 mediated inactivation of incretins like GLP-1 and GIPLabel,2. Incretins are released throughout the day and upregulated in response to meals as part of glucose homeostasisLabel,4. Reduced inhibition of incretins increase insulin synthesis and decrease glucagon release in a manner dependant on glucose concentrationsLabel,1. These effects lead to an overall increase in blood glucose control which is demonstrated by reduced glycosylated hemoglobin (HbA1c)Label,4.

TargetActionsOrganism
ADipeptidyl peptidase 4
inhibitor
Humans
Absorption

Sitagliptin is 87% orally bioavailable and taking it with or without food does not affect its pharmacokineticsLabel,4. Sitagliptin reaches maximum plasma concentration in 2 hours4.

Volume of distribution

198LLabel,4.

Protein binding

38%Label,4.

Metabolism

Sitagliptin is mostly not metabolised, with 79% of the dose excreted in the urine as the unchanged parent compoundLabel. Minor metabolic pathways are mediated mainly by cytochrome p450(CYP)3A4 and to a lesser extent by CYP2C8Label. After 18 hours, 81% of the dose has remained unchanged, while 2% has been N-sulfated to the M1 metabolite, 6% has been oxidatively desaturated and cyclized to the M2 metabolite, <1% glucuronidated at an unknown site to the M3 metabolite, <1% has been carbamoylated and glucuronidated to the M4 metabolite, 6% has been oxidatively saturated and cyclized to the M5 metabolite, and 2% has been hydroxylated at an unknown site to the M6 metabolite5. The M2 metabolite is the cis isomer while the M5 metabolite is the trans isomer of the same metabolite5.

Hover over products below to view reaction partners

Route of elimination

Approximately 79% of sitagliptin is excreted in the urine as the unchanged parent compoundLabel. 87% of the dose is eliminated in the urine and 13% in the fecesLabel,4.

Half-life

Approximately 12.4 hoursLabel. Other studies have reported a half life of approximately 11 hours4.

Clearance

350mL/minLabel,2.

Adverse Effects
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Toxicity

Animal studies in pregnancy have shown no adverse effects on the mother or offspring at normal doses, however these results are not always applicable to humansLabel. There is currently a voluntary registry of fetal exposureLabel,7. Animal studies at 100 times the maximum recommended human dose resulted in an increase in rib malformationsLabel. Sitagliptin is excreted in the milk of rats but it is not known if it would also be expressed in human breast milkLabel. Because many drugs are expressed in human breast milk, the risk and benefit of prescribing the medication must be consideredLabel. There is currently a lack of safety and effectiveness data in pediatric patientsLabel. No differences in safety and efficacy were observed in geriatric patients compared to younger patients, however caution should be used in this population as they are more likely to have reduced renal functionLabel. Sitagliptin has also been associated with a 34% relative risk increase for all cause infection4. There was no significant difference in patient response across sex, age, race, ethnicity, and BMI3.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Sitagliptin which could result in a higher serum level.
AbametapirThe serum concentration of Sitagliptin can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Sitagliptin can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Sitagliptin.
AbirateroneThe metabolism of Sitagliptin can be decreased when combined with Abiraterone.
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Sitagliptin.
AcebutololThe therapeutic efficacy of Sitagliptin can be increased when used in combination with Acebutolol.
AceclofenacAceclofenac may decrease the excretion rate of Sitagliptin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Sitagliptin which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Sitagliptin which could result in a higher serum level.
Additional Data Available
  • Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
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    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with or without food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Sitagliptin phosphateTS63EW8X6F654671-77-9GQPYTJVDPQTBQC-KLQYNRQASA-N
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
JanumetTablet, film coatedOralMerck Sharp & Dohme B.V.2008-07-16Not applicableEU flag
JanumetTablet, film coatedOralMerck Sharp & Dohme B.V.2008-07-16Not applicableEU flag
JanumetTablet, film coatedOralMerck Sharp & Dohme B.V.2008-07-16Not applicableEU flag
JanumetTablet, film coatedOralMerck Sharp & Dohme B.V.2008-07-16Not applicableEU flag
JanumetTablet, film coatedOralMerck Sharp & Dohme B.V.2008-07-16Not applicableEU flag
JanumetTablet, film coatedOralMerck Sharp & Dohme B.V.2008-07-16Not applicableEU flag
JanumetTablet, film coatedOralMerck Sharp & Dohme B.V.2008-07-16Not applicableEU flag
JanumetTablet, film coatedOralMerck Sharp & Dohme B.V.2008-07-16Not applicableEU flag
JanumetTablet, film coatedOralMerck Sharp & Dohme B.V.2008-07-16Not applicableEU flag
JanumetTablet, film coatedOralMerck Sharp & Dohme B.V.2008-07-16Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
JanumetSitagliptin phosphate (50 mg/1) + Metformin hydrochloride (1000 mg/1)Tablet, film coatedOralMed-Health Pharma, LLC2011-07-012012-07-18US flag
JanumetSitagliptin (50 mg) + Metformin hydrochloride (1000 mg)TabletOralMerck Ltd.2009-10-08Not applicableCanada flag
JanumetSitagliptin phosphate (50 mg/1) + Metformin hydrochloride (500 mg/1)Tablet, film coatedOralLake Erie Medical & Surgical Supply DBA Quality Care Products LLC2012-03-092014-12-31US flag00006 0575 61 nlmimage10 19160ce0
JanumetSitagliptin phosphate (50 mg/1) + Metformin hydrochloride (1000 mg/1)Tablet, film coatedOralMerck Sharp & Dohme Corp.2007-03-30Not applicableUS flag00006 0577 61 nlmimage10 1c160e30
JanumetSitagliptin phosphate (50 mg/1) + Metformin hydrochloride (1000 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2008-06-172013-06-30US flag
JanumetSitagliptin phosphate (50 mg/1) + Metformin hydrochloride (500 mg/1)Tablet, film coatedOralREMEDYREPACK INC.2013-02-212015-12-15US flag
JanumetSitagliptin phosphate (50 mg/1) + Metformin hydrochloride (500 mg/1)Tablet, film coatedOralMed-Health Pharma, LLC2011-07-012012-07-18US flag
JanumetSitagliptin (50 mg) + Metformin hydrochloride (850 mg)TabletOralMerck Ltd.2009-10-08Not applicableCanada flag
JanumetSitagliptin phosphate (50 mg/1) + Metformin hydrochloride (500 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2008-12-172012-06-30US flag
JanumetSitagliptin phosphate (50 mg/1) + Metformin hydrochloride (500 mg/1)Tablet, film coatedOralMerck Sharp & Dohme Corp.2007-03-30Not applicableUS flag0006 057520180810 16125 1fdkp22

Categories

ATC Codes
A10BH51 — Sitagliptin and simvastatinA10BD24 — Sitagliptin and ertugliflozinA10BD07 — Metformin and sitagliptinA10BH01 — SitagliptinA10BD12 — Pioglitazone and sitagliptin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as beta amino acids and derivatives. These are amino acids having a (-NH2) group attached to the beta carbon atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Beta amino acids and derivatives
Alternative Parents
Amphetamines and derivatives / Triazolopyrazines / Aralkylamines / Fluorobenzenes / Pyrazines / Aryl fluorides / Triazoles / Tertiary carboxylic acid amides / Heteroaromatic compounds / Azacyclic compounds
show 7 more
Substituents
1,2,4-triazole / Alkyl fluoride / Alkyl halide / Amine / Amphetamine or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
trifluorobenzene, triazolopyrazine (CHEBI:40237)

Chemical Identifiers

UNII
QFP0P1DV7Z
CAS number
486460-32-6
InChI Key
MFFMDFFZMYYVKS-SECBINFHSA-N
InChI
InChI=1S/C16H15F6N5O/c17-10-6-12(19)11(18)4-8(10)3-9(23)5-14(28)26-1-2-27-13(7-26)24-25-15(27)16(20,21)22/h4,6,9H,1-3,5,7,23H2/t9-/m1/s1
IUPAC Name
(3R)-3-amino-1-[3-(trifluoromethyl)-5H,6H,7H,8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one
SMILES
N[[email protected]@H](CC(=O)N1CCN2C(C1)=NN=C2C(F)(F)F)CC1=CC(F)=C(F)C=C1F

References

Synthesis Reference

Nurit Perlman, Marina Etinger, Valerie Niddam-Hildesheim, Mili Abramov, "Preparation of sitagliptin intermediate." U.S. Patent US20090192326, issued July 30, 2009.

US20090192326
General References
  1. Herman GA, Stevens C, Van Dyck K, Bergman A, Yi B, De Smet M, Snyder K, Hilliard D, Tanen M, Tanaka W, Wang AQ, Zeng W, Musson D, Winchell G, Davies MJ, Ramael S, Gottesdiener KM, Wagner JA: Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther. 2005 Dec;78(6):675-88. [PubMed:16338283]
  2. Herman GA, Bergman A, Liu F, Stevens C, Wang AQ, Zeng W, Chen L, Snyder K, Hilliard D, Tanen M, Tanaka W, Meehan AG, Lasseter K, Dilzer S, Blum R, Wagner JA: Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol. 2006 Aug;46(8):876-86. [PubMed:16855072]
  3. Karasik A, Aschner P, Katzeff H, Davies MJ, Stein PP: Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials. Curr Med Res Opin. 2008 Feb;24(2):489-96. doi: 10.1185/030079908X261069 . [PubMed:18182122]
  4. Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch C: Emerging role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes. Vasc Health Risk Manag. 2008;4(4):753-68. [PubMed:19065993]
  5. Vincent SH, Reed JR, Bergman AJ, Elmore CS, Zhu B, Xu S, Ebel D, Larson P, Zeng W, Chen L, Dilzer S, Lasseter K, Gottesdiener K, Wagner JA, Herman GA: Metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [14C]sitagliptin in humans. Drug Metab Dispos. 2007 Apr;35(4):533-8. doi: 10.1124/dmd.106.013136. Epub 2007 Jan 12. [PubMed:17220239]
  6. FDA Drug Approval Package: Sitagliptin [Link]
  7. Merck Pregnancy Registry: Sitagliptin [Link]
Human Metabolome Database
HMDB0015390
KEGG Drug
D08516
PubChem Compound
4369359
PubChem Substance
46505822
ChemSpider
3571948
BindingDB
11162
RxNav
593411
ChEBI
40237
ChEMBL
CHEMBL1422
ZINC
ZINC000001489478
Therapeutic Targets Database
DAP000639
PharmGKB
PA164748978
PDBe Ligand
715
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sitagliptin
AHFS Codes
  • 68:20.05 — Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
PDB Entries
1x70 / 4ffw
FDA label
Download (405 KB)
MSDS
Download (22.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionPosttransplant Diabetes Mellitus1
4Active Not RecruitingTreatmentType 2 Diabetes Mellitus2
4Active Not RecruitingTreatmentType II Diabetes in Subjects BMI 27 to 321
4CompletedNot AvailableHealthy Volunteers1
4CompletedBasic ScienceAtherosclerosis / Diabetes1
4CompletedBasic ScienceHealthy Volunteers1
4CompletedBasic ScienceHealthy Volunteers / Type 2 Diabetes Mellitus1
4CompletedBasic ScienceHigh Blood Pressure (Hypertension) / Metabolic Syndromes1
4CompletedBasic ScienceType 2 Diabetes Mellitus5
4CompletedOtherBMI >30 kg/m21

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Lake Erie Medical and Surgical Supply
  • Merck & Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Physicians Total Care Inc.
  • Resource Optimization and Innovation LLC
Dosage Forms
FormRouteStrength
Tablet, coatedOral5 mg
Tablet, coatedOral7.5 mg
TabletOral
Tablet, coatedOral1 g
Tablet, coatedOral500 mg
Tablet, coatedOral850 mg
Tablet, film coatedOral
Tablet, film coatedOral500 mg
Tablet, extended releaseOral
Tablet, film coated, extended releaseOral
Tablet, film coated, extended releaseOral1000 mg
Tablet, extended releaseOral50 mg
TabletOral100 mg
TabletOral25 mg
TabletOral50 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral100 mg
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral25 mg
Tablet, film coatedOral50 mg
Tablet, film coatedOral50 mg/1
Tablet, coatedOral100 mg
Tablet, film coated
Tablet, film coatedOral15 MG
Tablet, film coatedOral5 MG
Tablet, coatedOral25 MG
Tablet, coatedOral50 MG
Tablet, film coatedOral
Prices
Unit descriptionCostUnit
Januvia 90 25 mg tablet Bottle686.36USD bottle
Januvia 30 100 mg tablet Bottle228.81USD bottle
Januvia 50 mg tablet7.48USD tablet
Januvia 100 mg tablet7.33USD tablet
Januvia 25 mg tablet7.33USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2536251No2009-08-042024-08-27Canada flag
CA2450740No2006-02-142022-07-05Canada flag
US7326708No2008-02-052026-04-11US flag
US6699871No2004-03-022022-07-26US flag
US7125873No2006-10-242022-07-26US flag
US8414921No2013-04-092028-07-21US flag
US6340475No2002-01-222016-09-19US flag
US6635280No2003-10-212016-09-19US flag
US6303661No2001-10-162017-04-24US flag
US6890898No2005-05-102019-02-02US flag
US7078381No2006-07-182019-02-02US flag
US7459428No2008-12-022019-02-02US flag
US8168637No2012-05-012022-06-26US flag
US8080580No2011-12-202030-07-13US flag
US9439901No2016-09-132030-10-21US flag
US9308204No2016-04-122030-10-21US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP1.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.034 mg/mLALOGPS
logP1.95ALOGPS
logP1.26ChemAxon
logS-4.1ALOGPS
pKa (Strongest Basic)8.78ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area77.04 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity87.49 m3·mol-1ChemAxon
Polarizability32.66 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9438
Caco-2 permeable-0.6415
P-glycoprotein substrateSubstrate0.6509
P-glycoprotein inhibitor IInhibitor0.7141
P-glycoprotein inhibitor IIInhibitor0.5248
Renal organic cation transporterInhibitor0.592
CYP450 2C9 substrateNon-substrate0.9277
CYP450 2D6 substrateNon-substrate0.7228
CYP450 3A4 substrateSubstrate0.6412
CYP450 1A2 substrateNon-inhibitor0.7178
CYP450 2C9 inhibitorInhibitor0.6111
CYP450 2D6 inhibitorNon-inhibitor0.538
CYP450 2C19 inhibitorInhibitor0.7048
CYP450 3A4 inhibitorInhibitor0.5358
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8336
Ames testNon AMES toxic0.5487
CarcinogenicityNon-carcinogens0.7973
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8093 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7076
hERG inhibition (predictor II)Inhibitor0.6936
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0000900000-ce9211ae5927c697618c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-052r-0690500000-c28779e719a0e517d106
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0076-0930000000-1337dd7fb10ab92722b5
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00dl-0900000000-91485eb0052ad2f3637a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0900000000-7d92431093315efaed86
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0390000000-c8853d370b51f01b194b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000900000-2895dd4a879799635ae6
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-007c-0970100000-17431cd80097dff5c35f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00dl-0910000000-29041ebd42cb7f6026df
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-0900000000-dc60c3b1e5f0ba0e5e23
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0umi-0900000000-b1e1f886377c8d9b2a5d
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0900000000-d9e2b332d0ff3c6e283b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000900000-3403c0e74f19a7d0832a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-007c-0970000000-6aa1fc14d171d0102a2c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00dl-0910000000-62ba59074d19e0d89306
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-0900000000-91600010aa7e80c0e67c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0fmi-0900000000-d38f8b74df088a3b8232
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0900000000-08cf9f4ac284f2cd9057
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0390000000-b6e5cd73f4ff7abd2747

Targets

Details
1. Dipeptidyl peptidase 4
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Virus receptor activity
Specific Function
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by bindi...
Gene Name
DPP4
Uniprot ID
P27487
Uniprot Name
Dipeptidyl peptidase 4
Molecular Weight
88277.935 Da
References
  1. Herman GA, Stevens C, Van Dyck K, Bergman A, Yi B, De Smet M, Snyder K, Hilliard D, Tanen M, Tanaka W, Wang AQ, Zeng W, Musson D, Winchell G, Davies MJ, Ramael S, Gottesdiener KM, Wagner JA: Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther. 2005 Dec;78(6):675-88. [PubMed:16338283]
  2. Bergman AJ, Stevens C, Zhou Y, Yi B, Laethem M, De Smet M, Snyder K, Hilliard D, Tanaka W, Zeng W, Tanen M, Wang AQ, Chen L, Winchell G, Davies MJ, Ramael S, Wagner JA, Herman GA: Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers. Clin Ther. 2006 Jan;28(1):55-72. [PubMed:16490580]
  3. Gallwitz B: Therapies for the treatment of type 2 diabetes mellitus based on incretin action. Minerva Endocrinol. 2006 Jun;31(2):133-47. [PubMed:16682937]
  4. Herman GA, Bergman A, Liu F, Stevens C, Wang AQ, Zeng W, Chen L, Snyder K, Hilliard D, Tanen M, Tanaka W, Meehan AG, Lasseter K, Dilzer S, Blum R, Wagner JA: Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol. 2006 Aug;46(8):876-86. [PubMed:16855072]
  5. Miller S, St Onge EL: Sitagliptin: a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Ann Pharmacother. 2006 Jul-Aug;40(7-8):1336-43. [PubMed:16868220]
  6. Karasik A, Aschner P, Katzeff H, Davies MJ, Stein PP: Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials. Curr Med Res Opin. 2008 Feb;24(2):489-96. doi: 10.1185/030079908X261069 . [PubMed:18182122]
  7. Pratley RE, Salsali A: Inhibition of DPP-4: a new therapeutic approach for the treatment of type 2 diabetes. Curr Med Res Opin. 2007 Apr;23(4):919-31. [PubMed:17407649]
  8. Lyseng-Williamson KA: Sitagliptin. Drugs. 2007;67(4):587-97. [PubMed:17352516]
  9. Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab. 2007 Sep;9(5):733-45. Epub 2007 Jun 26. [PubMed:17593236]
  10. Gallwitz B: Sitagliptin: Profile of a novel DPP-4 inhibitor for the treatment of type 2 diabetes. Drugs Today (Barc). 2007 Jan;43(1):13-25. [PubMed:17315049]
  11. Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch C: Emerging role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes. Vasc Health Risk Manag. 2008;4(4):753-68. [PubMed:19065993]
  12. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Scheen AJ: Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58. doi: 10.1111/j.1463-1326.2010.01212.x. [PubMed:20590741]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Scheen AJ: Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58. doi: 10.1111/j.1463-1326.2010.01212.x. [PubMed:20590741]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Scheen AJ: Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58. doi: 10.1111/j.1463-1326.2010.01212.x. [PubMed:20590741]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Substrate profile was demonstrated in vitro using human OAT3 expressed on CHO-K1 cells.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [PubMed:19953504]

Drug created on May 16, 2007 11:36 / Updated on November 25, 2020 08:53

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