General
Preferred name
SITAGLIPTIN
Synonyms
SITAGLIPTIN PHOSPHATE ()
CHEMBL1422 ()
MK-0431 phosphate monohydrate ()
MK0431 phosphate ()
MK0431 ()
Januvia ()
Sitagliptin (phosphate) ()
Sitagliptin (phosphate monohydrate) ()
MK-0431 ()
MK-0431 (phosphate) ()
MK-0431 (phosphate monohydrate) ()
Sitagliptin phosphate monohydrate ()
LEZ-763 ()
LEZ763 ()
Janumet Xr ()
Sitagliptin monophosphate ()
Sitagliptin phosphate hydrate ()
Glactiv ()
Sitagliptin monophosphate anhydrous ()
Sitagliptin phosphate anhydrous ()
ONO-5435 ()
Sitagliptin monophosphate monohydrate ()
??(–)-Sitagliptin (phosphate) ()
P&D ID
PD003506
CAS
654671-78-0
790712-60-6
654671-77-9
1169707-31-6
486460-32-6
Tags
probe
natural product
drug
available
Approved by
EMA
FDA
First approval
2006
Drug Status
investigational
approved
Drug indication
Type-2 diabetes
Peripheral arterial disease
Max Phase
Phase 4
Probe info
Probe selectivity
protein-selective
Probe type
P&D approved
calculated probe
Probe sources
High-quality chemical probes
Tool Compound Set
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
2
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ROE
Approximately 79% of sitagliptin is excreted in the urine as the unchanged parent compound[Label]. 87% of the dose is eliminated in the urine and 13% in the feces[Label,A2260].
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 glucose[Label,A2260,A2255,A2256].
HALF-LIFE
Approximately 12.4 hours[Label]. Other studies have reported a half life of approximately 11 hours[A2260].
MOA
Inhibition of DPP-4 by sitagliptin slows DPP-4 mediated inactivation of incretins like GLP-1 and GIP[Label,A2256]. Incretins are released throughout the day and upregulated in response to meals as part of glucose homeostasis[Label,A2260]. Reduced inhibition of incretins increase insulin synthesis and decrease glucagon release in a manner dependant on glucose concentrations[Label,A2255]. These effects lead to an overall increase in blood glucose control which is demonstrated by reduced glycosylated hemoglobin (HbA1c)[Label,A2260].
INDICATION
Sitagliptin is indicated for the management of glycemic control in type 2 diabetes mellitus along with diet and exercise[Label].
METABOLISM
Sitagliptin is mostly not metabolised, with 79% of the dose excreted in the urine as the unchanged parent compound[Label]. Minor metabolic pathways are mediated mainly by cytochrome p450(CYP)3A4 and to a lesser extent by CYP2C8[Label]. 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 metabolite[A177649]. The M2 metabolite is the cis isomer while the M5 metabolite is the trans isomer of the same metabolite[A177649].
ABSORPTION
Sitagliptin is 87% orally bioavailable and taking it with or without food does not affect its pharmacokinetics[Label,A2260]. Sitagliptin reaches maximum plasma concentration in 2 hours[A2260].
DESCRIPTION
Sitagliptin is a dipeptidyl peptidase 4 (DPP4) inhibitor. Marketed formulations may contain sitagliptin phosphate monohydrate (PubChem CID 11591741).
(GtoPdb)
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 humans[Label]. There is currently a voluntary registry of fetal exposure[Label,L6067]. Animal studies at 100 times the maximum recommended human dose resulted in an increase in rib malformations[Label]. Sitagliptin is excreted in the milk of rats but it is not known if it would also be expressed in human breast milk[Label]. Because many drugs are expressed in human breast milk, the risk and benefit of prescribing the medication must be considered[Label]. There is currently a lack of safety and effectiveness data in pediatric patients[Label]. 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 function[Label]. Sitagliptin has also been associated with a 34% relative risk increase for all cause infection[A2260]. There was no significant difference in patient response across sex, age, race, ethnicity, and BMI[A2257].
DESCRIPTION
inhibitor of dipetidyl peptidase-4
(Informer Set)
DESCRIPTION
Zap70 inhibitor; inhibits interaction with ITAMs
(Tocris Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
35
Axon Medchem Screening Library
Cayman Chemical Bioactives
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
High-quality chemical probes
Informer Set
LSP-MoA library (Laboratory of Systems Pharmacology)
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocris Bioactive Compound Library
Tool Compound Set
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
81
Molecular Weight
407.12
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
1
Rotatable Bonds
4
Ring Count
3
Aromatic Ring Count
2
cLogP
2.02
TPSA
77.04
Fraction CSP3
0.44
Chiral centers
1.0
Largest ring
6.0
QED
0.62
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
DPP4
Dipeptidyl peptidase IV
DPP-4
DPP-4 inhibitor
Dipeptidyl Peptidase
DPP
Compound status
FDA
MOA
dipeptidyl peptidase 4 inhibitor
Inhibitor
Dipeptidyl Peptidase IV (CD26
DPP-IV
DP-IV) Inhibitors
dipeptidyl peptidase inhibitor
Pathway
Proteases/Proteasome
Autophagy
Metabolic Enzyme/Protease
Primary Target
Dipeptidyl Peptidase IV
Member status
virtual
Indication
diabetes mellitus
Therapeutic Indication
Antidiabetic
Therapeutic Class
Metabolic Disorders
Hypoglycemic Agents
VGSC Target
Nav1.5
Source data
