Identification

Name
Saxagliptin
Accession Number
DB06335
Type
Small Molecule
Groups
Approved
Description

Saxagliptin (rINN) is an orally active hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. FDA approved on July 31, 2009.

Structure
Thumb
Synonyms
  • (1S,3S,5S)-2-((2S)-Amino(3-hydroxytricyclo(3.3.1.13,7)dec-1-yl)acetyl)-2-azabicyclo(3.1.0)hexane-3-carbonitrile
  • Saxagliptin
  • Saxagliptin anhydrous
  • Saxagliptina
External IDs
BMS 477118 / BMS-477118
Product Ingredients
IngredientUNIICASInChI Key
Saxagliptin hydrochlorideZ8J84YIX6L709031-78-7TUAZNHHHYVBVBR-NHKADLRUSA-N
Saxagliptin monohydrate9GB927LAJW945667-22-1AFNTWHMDBNQQPX-NHKADLRUSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
OnglyzaTablet5 mgOralAstra Zeneca2009-10-29Not applicableCanada
OnglyzaTablet, film coated2.5 mgOralAstra Zeneca Ab2009-10-01Not applicableEu
OnglyzaTablet, film coated5 mg/1OralE.R. Squibb & Sons, L.L.C.2009-07-312017-04-30Us00003 4215 11 nlmimage10 c33ce1e7
OnglyzaTablet, film coated5 mgOralAstra Zeneca Ab2009-10-01Not applicableEu
OnglyzaTablet, film coated5 mgOralAstra Zeneca Ab2009-10-01Not applicableEu
OnglyzaTablet, film coated2.5 mgOralAstra Zeneca Ab2009-10-01Not applicableEu
OnglyzaTablet, film coated5 mg/1OralCardinal Health2009-07-312017-04-30Us55154 061120180907 15195 1oaui6w
OnglyzaTablet, film coated5 mgOralAstra Zeneca Ab2009-10-01Not applicableEu
OnglyzaTablet, film coated2.5 mgOralAstra Zeneca Ab2009-10-01Not applicableEu
OnglyzaTablet, film coated5 mg/1OralAstra Zeneca Lp2014-11-20Not applicableUs0310 610520180913 8702 13a6565
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Kombiglyze XRSaxagliptin hydrochloride (5 mg/1) + Metformin Hydrochloride (500 mg/1)Tablet, film coated, extended releaseOralAstraZeneca Pharmaceuticals LP2014-12-04Not applicableUs
Kombiglyze XRSaxagliptin hydrochloride (5 mg/1) + Metformin Hydrochloride (1000 mg/1)Tablet, film coated, extended releaseOralE.R. Squibb & Sons, L.L.C.2010-11-052017-03-31Us
Kombiglyze XRSaxagliptin hydrochloride (5 mg/1) + Metformin Hydrochloride (500 mg/1)Tablet, film coated, extended releaseOralE.R. Squibb & Sons, L.L.C.2010-11-052017-04-30Us
Kombiglyze XRSaxagliptin hydrochloride (5 mg/1) + Metformin Hydrochloride (1000 mg/1)Tablet, film coated, extended releaseOralAstraZeneca Pharmaceuticals LP2014-12-04Not applicableUs
Kombiglyze XRSaxagliptin hydrochloride (2.5 mg/1) + Metformin Hydrochloride (1000 mg/1)Tablet, film coated, extended releaseOralE.R. Squibb & Sons, L.L.C.2010-11-052017-05-31Us00003 4222 16 nlmimage10 f215f93f
Kombiglyze XRSaxagliptin hydrochloride (2.5 mg/1) + Metformin Hydrochloride (1000 mg/1)Tablet, film coated, extended releaseOralAstraZeneca Pharmaceuticals LP2014-12-04Not applicableUs00310 6125 60 nlmimage10 d049e84f
KomboglyzeSaxagliptin (2.5 mg) + Metformin Hydrochloride (500 mg)TabletOralAstra Zeneca2013-04-26Not applicableCanada
KomboglyzeSaxagliptin (2.5 mg) + Metformin (1000 mg)Tablet, film coatedOralAstra Zeneca Ab2011-11-24Not applicableEu
KomboglyzeSaxagliptin (2.5 mg) + Metformin (850 mg)Tablet, film coatedOralAstra Zeneca Ab2011-11-24Not applicableEu
KomboglyzeSaxagliptin (2.5 mg) + Metformin Hydrochloride (1000 mg)TabletOralAstra Zeneca2013-04-26Not applicableCanada
Categories
UNII
8I7IO46IVQ
CAS number
361442-04-8
Weight
Average: 315.41
Monoisotopic: 315.194677059
Chemical Formula
C18H25N3O2
InChI Key
QGJUIPDUBHWZPV-SGTAVMJGSA-N
InChI
InChI=1S/C18H25N3O2/c19-8-13-2-12-3-14(12)21(13)16(22)15(20)17-4-10-1-11(5-17)7-18(23,6-10)9-17/h10-15,23H,1-7,9,20H2/t10?,11?,12-,13+,14+,15-,17?,18?/m1/s1
IUPAC Name
(1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile
SMILES
N[C@H](C(=O)N1[C@H]2C[C@H]2C[C@H]1C#N)C12CC3CC(CC(O)(C3)C1)C2

Pharmacology

Indication

Treatment of type 2 diabetes mellitus to improve glycemic control in combination with other agents or as monotherapy.

Associated Conditions
Pharmacodynamics

Post-administration of saxagliptin, GLP-1 and GIP levels rise up to 2- to 3- fold. Because it is very selective of DPP-4 inhibition, there are fewer systemic side effects. Saxagliptin inhibits DPP-4 enzyme activity for a 24-hour period. It also decreased glucagon concentrations and increased glucose-dependent insulin secretion from pancreatic beta cells. The half maximal inhibitory concentration (IC50) is 0.5 nmol/L. Saxagliptin did not prolong the QTc interval to a clinically significant degree.

Mechanism of action

Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor antidiabetic for the treatment of type 2 diabetes. DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver. [Bristol-Myers Squibb Press Release] DPP-4 is a membrane associated peptidase which is found in many tissues, lymphocytes and plasma. DPP-4 has two main mechanisms of action, an enzymatic function and another mechanism where DPP-4 binds adenosine deaminase, which conveys intracellular signals via dimerization when activated. Saxagliptin forms a reversible, histidine-assisted covalent bond between its nitrile group and the S630 hydroxyl oxygen on DPP-4. The inhibition of DPP-4 increases levels active of glucagon like peptide 1 (GLP-1), which inhibits glucagon production from pancreatic alpha cells and increases production of insulin from pancreatic beta cells.

TargetActionsOrganism
ADipeptidyl peptidase 4
inhibitor
Human
Absorption

Following a 5 mg single oral dose of saxagliptin to healthy subjects, the mean plasma AUC values for saxagliptin and its active metabolite were 78 ng•h/mL and 214 ng•h/mL, respectively. The corresponding plasma Cmax values were 24 ng/mL and 47 ng/mL, respectively. Saxagliptin did not accumulate following repeated doses. The median time to maximum concentration (Tmax) following the 5 mg once daily dose was 2 hours for saxagliptin and 4 hours for its active metabolite. Bioavailability, 2.5 - 50 mg dose = 67%

Volume of distribution

151 L

Protein binding

The in vitro protein binding of saxagliptin and its active metabolite in human serum is negligible (<10%).

Metabolism

The metabolism of saxagliptin is primarily mediated by cytochrome P450 3A4/5 (CYP3A4/5). 50% of the absorbed dose will undergo hepatic metabolism. The major metabolite of saxagliptin, 5-hydroxy saxagliptin, is also a DPP4 inhibitor, which is one-half as potent as saxagliptin.

Route of elimination

Saxagliptin is eliminated by both renal and hepatic pathways. Following a single 50 mg dose of 14C-saxagliptin, 24%, 36%, and 75% of the dose was excreted in the urine as saxagliptin, its active metabolite, and total radioactivity, respectively. A total of 22% of the administered radioactivity was recovered in feces representing the fraction of the saxagliptin dose excreted in bile and/or unabsorbed drug from the gastrointestinal tract.

Half life

Saxagliptin = 2.5 hours; 5-hydroxy saxagliptin = 3.1 hours;

Clearance

Renal clearance, single 50 mg dose = 14 L/h

Toxicity

Adverse reactions reported in ≥5% of patients treated with saxagliptin and more commonly than in patients treated with placebo are: upper respiratory tract infection, urinary tract infection, and headache.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Saxagliptin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Saxagliptin.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Saxagliptin is combined with 2,4-thiazolidinedione.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Saxagliptin.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Saxagliptin.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Saxagliptin can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
5-androstenedioneThe metabolism of Saxagliptin can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Saxagliptin can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Saxagliptin.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Saxagliptin.
Food Interactions
  • Administration with a high-fat meal resulted in an increase in Tmax of saxagliptin by approximately 20 minutes as compared to fasted conditions. There was a 27% increase in the AUC of saxagliptin when given with a meal as compared to fasted conditions.

References

Synthesis Reference

Jack Z. Gougoutas, Mary F. Malley, John D. DiMarco, Xiaotian S. Yin, Chenkou Wei, Jurong Yu, Truc Chi Vu, Gregory Scott Jones, Scott A. Savage, "CRYSTAL FORMS OF SAXAGLIPTIN AND PROCESSES FOR PREPARING SAME." U.S. Patent US20090054303, issued February 26, 2009.

US20090054303
General References
  1. Rosenstock J, Sankoh S, List JF: Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab. 2008 May;10(5):376-86. doi: 10.1111/j.1463-1326.2008.00876.x. Epub 2008 Mar 18. [PubMed:18355324]
  2. Metzler WJ, Yanchunas J, Weigelt C, Kish K, Klei HE, Xie D, Zhang Y, Corbett M, Tamura JK, He B, Hamann LG, Kirby MS, Marcinkeviciene J: Involvement of DPP-IV catalytic residues in enzyme-saxagliptin complex formation. Protein Sci. 2008 Feb;17(2):240-50. doi: 10.1110/ps.073253208. [PubMed:18227430]
  3. Crepaldi G, Carruba M, Comaschi M, Del Prato S, Frajese G, Paolisso G: Dipeptidyl peptidase 4 (DPP-4) inhibitors and their role in Type 2 diabetes management. J Endocrinol Invest. 2007 Jul-Aug;30(7):610-4. [PubMed:17848846]
  4. Barnett A: DPP-4 inhibitors and their potential role in the management of type 2 diabetes. Int J Clin Pract. 2006 Nov;60(11):1454-70. [PubMed:17073841]
  5. Kulasa K, Edelman S: Saxagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus. Core Evid. 2010 Oct 21;5:23-37. [PubMed:21042540]
  6. Russell S: Incretin-based therapies for type 2 diabetes mellitus: a review of direct comparisons of efficacy, safety and patient satisfaction. Int J Clin Pharm. 2013 Apr;35(2):159-72. doi: 10.1007/s11096-012-9729-9. Epub 2012 Dec 22. [PubMed:23263796]
  7. Ali S, Fonseca V: Saxagliptin overview: special focus on safety and adverse effects. Expert Opin Drug Saf. 2013 Jan;12(1):103-9. doi: 10.1517/14740338.2013.741584. Epub 2012 Nov 9. [PubMed:23137182]
  8. Golightly LK, Drayna CC, McDermott MT: Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet. 2012 Aug 1;51(8):501-14. doi: 10.2165/11632930-000000000-00000. [PubMed:22686547]
External Links
Human Metabolome Database
HMDB0015634
KEGG Drug
D08996
PubChem Compound
11243969
PubChem Substance
99443245
ChemSpider
9419005
BindingDB
11542
ChEBI
71272
ChEMBL
CHEMBL385517
PharmGKB
PA165958362
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Saxagliptin
ATC Codes
A10BH03 — SaxagliptinA10BD10 — Metformin and saxagliptinA10BD21 — Saxagliptin and dapagliflozin
AHFS Codes
  • 68:20.05 — Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
FDA label
Download (492 KB)
MSDS
Download (479 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentType 2 Diabetes Mellitus1
1CompletedNot AvailableDiabetes Mellitus (DM)3
1CompletedNot AvailableType 2 Diabetes Mellitus8
1CompletedBasic ScienceBioequivalence, Log-transformed AUCss and Cmax,ss Values for Saxagliptin and Metformin1
1CompletedBasic ScienceType 2 Diabetes Mellitus3
1CompletedTreatmentType 2 Diabetes Mellitus2
1TerminatedNot AvailableType 2 Diabetes Mellitus1
1WithdrawnNot AvailableType 2 Diabetes Mellitus1
2Active Not RecruitingTreatmentInsulin Resistance / Type 2 Diabetes Mellitus1
2CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
2CompletedTreatmentImpaired Glucose Tolerance (IGT)1
2CompletedTreatmentType 2 Diabetes Mellitus2
2RecruitingTreatmentGlucose, Low Blood1
2, 3CompletedTreatmentType 2 Diabetes Mellitus, CKD and Albuminuria / Type 2 Diabetes Mellitus, CKD3 and Albuminuria1
3Active Not RecruitingTreatmentDiabetes Mellitus (DM)1
3CompletedOtherDiabetes Mellitus (DM)1
3CompletedPreventionDiabetes, Diabetes Mellitus Type 1 / Hypoglycemia1
3CompletedTreatmentDiabetes Mellitus (DM)3
3CompletedTreatmentDisorder of Glucose Regulation / Polycystic Ovaries Syndrome1
3CompletedTreatmentInadequate Glycaemic Control / Type 2 Diabetes Mellitus / Type2 Diabetes Mellitus1
3CompletedTreatmentType 2 Diabetes Mellitus28
3Not Yet RecruitingTreatmentType 2 Diabetes Mellitus2
3RecruitingTreatmentType 2 Diabetes Mellitus1
4Active Not RecruitingNot AvailableType 2 Diabetes Mellitus1
4Active Not RecruitingTreatmentType 2 Diabetes Mellitus2
4CompletedBasic ScienceType 2 Diabetes Mellitus1
4CompletedTreatmentBMI >30 kg/m2 / Pre-Diabetic1
4CompletedTreatmentCoronary Artery Disease / Type 2 Diabetes Mellitus1
4CompletedTreatmentDiabetes Mellitus, Non-Insulin-Dependent1
4CompletedTreatmentInadequate Glycaemic Control / Type 2 Diabetes Mellitus / Type2 Diabetes Mellitus1
4CompletedTreatmentType 2 Diabetes Mellitus7
4CompletedTreatmentType2 Diabetes Mellitus1
4Enrolling by InvitationBasic ScienceHypertriglyceridemias / Type 2 Diabetes Mellitus1
4Enrolling by InvitationTreatmentMicroalbuminuria / Microalbuminuria /Creatinine Ratios ACR1
4Not Yet RecruitingTreatmentBMI >30 kg/m2 / Type 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentCardiovascular Disease (CVD) / Type 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentType 2 Diabetes Mellitus2
4RecruitingTreatmentDiabetes Mellitus (DM)1
4RecruitingTreatmentDiabetes Mellitus, Non-Insulin-Dependent / Heart Failure, Unspecified1
4RecruitingTreatmentDiabetes, Diabetes Mellitus Type 12
4RecruitingTreatmentDiabetic Foot Ulcers (DFU)1
4RecruitingTreatmentHeart Failure, Unspecified / Type 2 Diabetes Mellitus1
4RecruitingTreatmentType 2 Diabetes Mellitus2
4TerminatedNot AvailableCardiovascular Disease (CVD) / Type 2 Diabetes Mellitus1
4TerminatedTreatmentImpaired Glucose Tolerance (IGT)1
4Unknown StatusNot AvailableType 2 Diabetes Mellitus1
4Unknown StatusTreatmentPre-Diabetic1
4Unknown StatusTreatmentSevere Hyperglycemia - Blood Glucose Level >300mg/dl / Type 2 Diabetes Mellitus1
4Unknown StatusTreatmentType 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus5
Not AvailableRecruitingPreventionIncretinomimetics / Pancreas / Type 2 Diabetes Mellitus1
Not AvailableRecruitingTreatmentImpaired Fasting Glucose (IFG) / Impaired Glucose Tolerance (IGT) / Type 2 Diabetes Mellitus1
Not AvailableRecruitingTreatmentType 2 Diabetes Mellitus2
Not AvailableUnknown StatusSupportive CareCystic Fibrosis (CF)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coated, extended releaseOral
TabletOral
Tablet, film coatedOral
TabletOral2.5 mg
TabletOral5 mg
Tablet, film coatedOral2.5 mg/1
Tablet, film coatedOral2.5 mg
Tablet, film coatedOral5 mg
Tablet, film coatedOral5 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6395767No2002-05-282021-02-16Us
USRE44186No2013-04-302023-07-31Us
US7951400No2011-05-312028-11-30Us
US8628799No2014-01-142025-07-13Us
US8501698No2013-08-062027-06-20Us
US6414126No2002-07-022020-10-04Us
US6515117No2003-02-042020-10-04Us
US6936590No2005-08-302020-10-04Us
US9198925No2015-12-012020-10-04Us
US7919598No2011-04-052029-12-16Us
US8361972No2013-01-292028-03-21Us
US8716251No2014-05-062028-03-21Us
US8221786No2012-07-172028-03-21Us
US9339472No2016-05-172025-07-13Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySparingly solubleFDA label
Predicted Properties
PropertyValueSource
Water Solubility2.26 mg/mLALOGPS
logP0.88ALOGPS
logP-0.08ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)14.74ChemAxon
pKa (Strongest Basic)7.9ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area90.35 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity83.99 m3·mol-1ChemAxon
Polarizability34.22 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9894
Blood Brain Barrier+0.8823
Caco-2 permeable-0.5446
P-glycoprotein substrateSubstrate0.5909
P-glycoprotein inhibitor INon-inhibitor0.696
P-glycoprotein inhibitor IINon-inhibitor0.7875
Renal organic cation transporterNon-inhibitor0.7903
CYP450 2C9 substrateNon-substrate0.8618
CYP450 2D6 substrateNon-substrate0.7519
CYP450 3A4 substrateSubstrate0.5944
CYP450 1A2 substrateNon-inhibitor0.8448
CYP450 2C9 inhibitorNon-inhibitor0.8017
CYP450 2D6 inhibitorNon-inhibitor0.8198
CYP450 2C19 inhibitorNon-inhibitor0.81
CYP450 3A4 inhibitorNon-inhibitor0.8641
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9032
Ames testNon AMES toxic0.7569
CarcinogenicityNon-carcinogens0.9122
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7529 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9912
hERG inhibition (predictor II)Non-inhibitor0.832
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid amides
Alternative Parents
N-acylpiperidines / N-acylpyrrolidines / Tertiary carboxylic acid amides / Tertiary alcohols / Cyclic alcohols and derivatives / Nitriles / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Monoalkylamines
show 2 more
Substituents
Alpha-amino acid amide / N-acyl-piperidine / N-acylpyrrolidine / Piperidine / Cyclic alcohol / Pyrrolidine / Tertiary carboxylic acid amide / Tertiary alcohol / Carboxamide group / Carbonitrile
show 16 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
tertiary alcohol, azabicycloalkane, monocarboxylic acid amide, adamantanes, nitrile (CHEBI:71272)

Targets

Details
1. Dipeptidyl peptidase 4
Kind
Protein
Organism
Human
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. Augeri DJ, Robl JA, Betebenner DA, Magnin DR, Khanna A, Robertson JG, Wang A, Simpkins LM, Taunk P, Huang Q, Han SP, Abboa-Offei B, Cap M, Xin L, Tao L, Tozzo E, Welzel GE, Egan DM, Marcinkeviciene J, Chang SY, Biller SA, Kirby MS, Parker RA, Hamann LG: Discovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem. 2005 Jul 28;48(15):5025-37. [PubMed:16033281]

Enzymes

Kind
Protein
Organism
Human
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. Upreti VV, Boulton DW, Li L, Ching A, Su H, Lacreta FP, Patel CG: Effect of rifampicin on the pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in healthy subjects. Br J Clin Pharmacol. 2011 Jul;72(1):92-102. doi: 10.1111/j.1365-2125.2011.03937.x. [PubMed:21651615]
  2. Patel CG, Kornhauser D, Vachharajani N, Komoroski B, Brenner E, Handschuh del Corral M, Li L, Boulton DW: Saxagliptin, a potent, selective inhibitor of DPP-4, does not alter the pharmacokinetics of three oral antidiabetic drugs (metformin, glyburide or pioglitazone) in healthy subjects. Diabetes Obes Metab. 2011 Jul;13(7):604-14. doi: 10.1111/j.1463-1326.2011.01381.x. [PubMed:21332626]
  3. Scheen AJ: Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacokinet. 2010 Sep;49(9):573-88. doi: 10.2165/11532980-000000000-00000. [PubMed:20690781]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Upreti VV, Boulton DW, Li L, Ching A, Su H, Lacreta FP, Patel CG: Effect of rifampicin on the pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in healthy subjects. Br J Clin Pharmacol. 2011 Jul;72(1):92-102. doi: 10.1111/j.1365-2125.2011.03937.x. [PubMed:21651615]
  2. Patel CG, Kornhauser D, Vachharajani N, Komoroski B, Brenner E, Handschuh del Corral M, Li L, Boulton DW: Saxagliptin, a potent, selective inhibitor of DPP-4, does not alter the pharmacokinetics of three oral antidiabetic drugs (metformin, glyburide or pioglitazone) in healthy subjects. Diabetes Obes Metab. 2011 Jul;13(7):604-14. doi: 10.1111/j.1463-1326.2011.01381.x. [PubMed:21332626]
  3. Scheen AJ: Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacokinet. 2010 Sep;49(9):573-88. doi: 10.2165/11532980-000000000-00000. [PubMed:20690781]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Scheen AJ: Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacokinet. 2010 Sep;49(9):573-88. doi: 10.2165/11532980-000000000-00000. [PubMed:20690781]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Organic anion transporter, capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. May participate in the regulation of membrane transport of ...
Gene Name
SLCO4C1
Uniprot ID
Q6ZQN7
Uniprot Name
Solute carrier organic anion transporter family member 4C1
Molecular Weight
78947.525 Da
References
  1. Golightly LK, Drayna CC, McDermott MT: Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet. 2012 Aug 1;51(8):501-14. doi: 10.2165/11632930-000000000-00000. [PubMed:22686547]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. Golightly LK, Drayna CC, McDermott MT: Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet. 2012 Aug 1;51(8):501-14. doi: 10.2165/11632930-000000000-00000. [PubMed:22686547]

Drug created on March 19, 2008 10:24 / Updated on December 14, 2018 12:41