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Sitagliptin

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Also known as LEZ-763LEZ763Sitagliptin component of zituvimetSitagliptinaSitagliptineZituvioSID174006349SITAGLIPTIN PHOSPHATE

Summary

Sitagliptin (CHEMBL1422) is an approved small-molecule serine proteinase inhibitor (ATC A10BH01) targeting DPP4; indicated across 24 conditions including diabetes mellitus and chronic kidney disease.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: A10BH01
  • Targets: 1 (DPP4)
  • Indications: 24 conditions
  • Clinical trials: 420
  • Chemistry: 407.31 Da · C16H15F6N5O

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL1422
NameSitagliptin
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID4369359
ChEBICHEBI:40237
ATCA10BH01
Molecular formulaC16H15F6N5O
Molecular weight407.31
InChIKeyMFFMDFFZMYYVKS-SECBINFHSA-N

SMILES: C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)C[C@@H](CC3=CC(=C(C=C3F)F)F)N

IUPAC name: (3R)-3-amino-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one

ChEBI definition: A triazolopyrazine that exhibits hypoglycemic activity.

Pharmacological roles (ChEBI): serine proteinase inhibitor, hypoglycemic agent, EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor.

Also known as: LEZ-763, LEZ763, Sitagliptin, Sitagliptin component of zituvimet, Sitagliptina, Sitagliptine, Zituvio, sitagliptine, sitagliptin, SID174006349, SITAGLIPTIN, SITAGLIPTIN PHOSPHATE

Parent form; salt/anhydrous children: CHEMBL393336, CHEMBL539077, CHEMBL1201174, CHEMBL5315049, CHEMBL6068334

Patent coverage: 7,217 distinct patent families (26,582 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 26,501 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
DPP4dipeptidyl peptidase 4Inhibition8.10%P27487

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Angiotensin-converting enzyme, 5-hydroxytryptamine receptor 2A, Dipeptidyl peptidase 4, Dipeptidyl peptidase 4, Dipeptidyl peptidase 2, Dipeptidyl peptidase 4, Dipeptidyl peptidase 8, Prolyl endopeptidase FAP, Dipeptidyl peptidase 9.

Bioactivity

ChEMBL activities: 75 potent at pChembl ≥ 5 of 96 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
DPP49.06IC500.87nMCHEMBL_ACT_25050676
DPP48.46IC503.5nMCHEMBL_ACT_6335420
DPP48.28Kd5.3nMCHEMBL_ACT_19442627
DPP48.21IC506.24nMCHEMBL_ACT_16763207
DPP48.16IC506.9nMCHEMBL_ACT_19301473
DPP48.15IC507nMCHEMBL_ACT_13903931
DPP48.11IC507.8nMCHEMBL_ACT_18662285
DPP48.11IC507.8nMCHEMBL_ACT_22483380
DPP48.1IC508nMCHEMBL_ACT_26141942
DPP48.1IC508nMCHEMBL_ACT_29231848
DPP48.08IC508.4nMCHEMBL_ACT_22463737
DPP48.06IC508.8nMCHEMBL_ACT_24719112
DPP48IC5010nMCHEMBL_ACT_13903927
DPP47.92IC5012nMCHEMBL_ACT_15714328
DPP47.9Kd12.7nMCHEMBL_ACT_16763210
DPP47.9Kd12.7nMCHEMBL_ACT_19483873
DPP47.87Kd13.5nMCHEMBL_ACT_19442663
DPP47.85IC5014nMCHEMBL_ACT_27811433
P288437.83IC5014.7nMCHEMBL_ACT_18977499
DPP47.8IC5016nMCHEMBL_ACT_15178636
DPP47.8IC5016nMCHEMBL_ACT_25636157
DPP47.77IC5017nMCHEMBL_ACT_16823214
DPP47.75IC5018nMCHEMBL_ACT_12044050
DPP47.75IC5018nMCHEMBL_ACT_14579417
DPP47.75IC5018nMCHEMBL_ACT_14597076
DPP47.75IC5018nMCHEMBL_ACT_15010457
DPP47.75IC5018nMCHEMBL_ACT_15722595
DPP47.75IC5018nMCHEMBL_ACT_15762424
DPP47.75IC5018nMCHEMBL_ACT_1792470
DPP47.75IC5018nMCHEMBL_ACT_1958927

Target pathways

Aggregated over 1 target gene(s): DPP4.

Top Reactome pathways

2 total, by targets touching each:

PathwayTargetsGenes
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)1DPP4
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)1DPP4

Dominant GO biological processes

GO termTargets
behavioral fear response1
response to hypoxia1
proteolysis1
cell adhesion1
positive regulation of cell population proliferation1
negative regulation of extracellular matrix disassembly1
peptide hormone processing1
receptor-mediated endocytosis of virus by host cell1
T cell costimulation1
regulation of cell-cell adhesion mediated by integrin1
locomotory exploration behavior1
psychomotor behavior1
T cell activation1
endothelial cell migration1
symbiont entry into host cell1

Indications & clinical

Indications

24 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
diabetes mellitus4MONDO:0005015EFO:0000400
chronic kidney disease3MONDO:0005300EFO:0003884
graft versus host disease3MONDO:0013730MONDO:0013730
severe acute respiratory syndrome3MONDO:0005091MONDO:0100096
acute myocardial infarction3MONDO:0004781EFO:0008583
type 2 diabetes mellitus3MONDO:0005148MONDO:0005148
HIV infectious disease2MONDO:0005109EFO:0000180
psoriasis2MONDO:0005083EFO:0000676
metabolic dysfunction-associated steatotic liver disease2MONDO:0013209EFO:0003095
glucose intolerance2MONDO:0001076EFO:0002546
prediabetes syndrome2MONDO:0006920EFO:1001121
obesity disorder2MONDO:0011122EFO:0001073
type 1 diabetes mellitus2MONDO:0005147MONDO:0005147
cystic fibrosis2MONDO:0009061MONDO:0009061
hyperlipidemia2MONDO:0021187MONDO:0021187
polycystic ovary syndrome2MONDO:0008487EFO:0000660
metabolic dysfunction-associated steatohepatitis2MONDO:0007027EFO:1001249
pancreatic ductal adenocarcinoma2MONDO:0005184MONDO:0005184
hepatitis C virus infection1MONDO:0005231EFO:0003047
hepatocellular carcinoma1MONDO:0007256EFO:0000182
congestive heart failure0MONDO:0005009EFO:0000373

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 420.

Phase distribution

PhaseTrials
PHASE4120
PHASE3120
Not specified63
PHASE252
PHASE145
PHASE2/PHASE310
PHASE1/PHASE27
EARLY_PHASE13

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04323189PHASE4ACTIVE_NOT_RECRUITINGEffects of Sitagliptin in Individuals With Genetically Decreased DPP4
NCT05195944PHASE4ENROLLING_BY_INVITATIONSemaglutide vs Sitagliptin
NCT06851962PHASE4ACTIVE_NOT_RECRUITINGImpact of Pharmacogenetic-Guided Treatment on Type 2 Diabetes.
NCT06972732PHASE4RECRUITINGA Phase IV Clinical Trial to Compare the Efficacy and Safety of Metformin+Sodium-Glucose Cotransporter 2 Inhibitor(SGLT2-i)+Thiazolidinedione (TZD) in Patients With Type 2 Diabetes
NCT07108985PHASE4NOT_YET_RECRUITINGEffect of Add-on SGLT2i, TZD, or Combination Therapy in Type 2 Diabetes Patients on DPP4 Inhibitors
NCT07436663PHASE4NOT_YET_RECRUITINGComparative Study Between (SGLT-2i) and (DPP-4i) in the Prevention of DIC
NCT07452913PHASE4ENROLLING_BY_INVITATIONMetformin, Empagliflozin With Sitagliptin vs Linagliptin in Type 2 Diabetes
NCT00364377PHASE4COMPLETEDIncretins in Impaired Fasting Glucose
NCT00477581PHASE4COMPLETEDA Study to Compare the Effects of Exenatide and Sitagliptin on Postprandial Glucose in Subjects With Type 2 Diabetes Mellitus
NCT00627744PHASE4COMPLETEDBeta-cell Function in Glucose Abnormalities and Acute Myocardial Infarction
NCT00666848PHASE4COMPLETEDEffect of Sitagliptin and an ACE Inhibitor on Blood Pressure in Metabolic Syndrome
NCT00686634PHASE4COMPLETEDSitagliptin in Combination With Metformin and Sulfonylurea
NCT00699322PHASE4UNKNOWNEffect of Dipeptidyl Peptidase-IV Inhibitor and Sulfonylurea on Glucose Variability and Oxidative Stress
NCT00729326PHASE4COMPLETEDComparison of the Effect of Exenatide Versus Sitagliptin on 24-hour Average Glucose in Patients With Type 2 Diabetes on Metformin or a Thiazolidinedione
NCT00732121PHASE4UNKNOWNBone Turnover in Type 2 Diabetes Patients
NCT00740363PHASE4COMPLETEDSitagliptin in Renal Transplant Recipients
NCT00751114PHASE4COMPLETEDEvaluation of Insulin Glargine Versus Sitagliptin in Insulin-naive Patients
NCT00766441PHASE4TERMINATEDSitagliptin Versus Sulphonylurea in Type 2 Diabetes During Ramadan
NCT00780715PHASE4COMPLETEDResponse To Oral Agents in Diabetes (ROAD)- Pilot Study
NCT00820573PHASE4COMPLETEDMechanisms of Glucose Lowering Effects of Sitagliptin and Metformin Alone and in Combination in Patients With T2DM
NCT00832390PHASE4COMPLETEDStudy to Assess the Efficacy and Safety of Sitagliptin in Recently Diagnosed, Naive Type 2 Diabetics With Inadequate Glycemic Control on Diet and Exercise (0431-158)
NCT00832624PHASE4TERMINATEDThe Effect of Sitagliptin in Type 2 Diabetes Mellitus With Inadequate Glycemic Control (MK0431-118)
NCT00833027PHASE4COMPLETEDALPHA Sitagliptin Add on to Metformin (0431-103)
NCT00847080PHASE4COMPLETEDTreatment With Sitagliptin for Reactive Hypoglycemia Secondary to Dysinsulinism
NCT00870194PHASE4COMPLETEDA Comparison of Adding Exenatide With Switching to Exenatide in Patients With Type 2 Diabetes Experiencing Inadequate Glycemic Control With Sitagliptin Plus Metformin
NCT00885638PHASE4COMPLETEDEffects of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Hormonal Responses to Macronutrient Ingestion
NCT00936663PHASE4TERMINATEDUsing Sitagliptin as a Treatment to Prevent New Onset Diabetes After Kidney Transplantation
NCT00939939PHASE4TERMINATEDEffect of Sitagliptin on Postprandial Lipoprotein Metabolism
NCT00957060PHASE4COMPLETEDSuperiority of Glimepiride Over Sitagliptin in Naive Type 2 Diabetes Patients
NCT00968006PHASE4COMPLETEDEffect of Sitagliptin on Endothelial Progenitor Cells
NCT00969566PHASE4COMPLETEDPredictive Parameters for Efficacy of Sitagliptin and Metformin Combination
NCT00978796PHASE4COMPLETEDAssessing Glucose Effects of Sitagliptin (Januvia) in Adult Patients With Type 1 Diabetes
NCT00993187PHASE4COMPLETEDEfficacy and Safety of Sitagliptin/Metformin Fixed-Dose Combination (FDC) Compared to Glimepiride in Participants With Type 2 Diabetes Mellitus (MK-0431A-202)
NCT01096277PHASE4UNKNOWNVascular Effects of Sitagliptin in Diabetes Mellitus
NCT01099618PHASE4COMPLETEDKetosis-Prone Diabetes Mellitus (KPDM): Metformin Versus Sitagliptin Treatment
NCT01100125PHASE4COMPLETEDSitagliptin Versus Insulin Dose Increase in Type 2 Diabetes on Insulin Treatment
NCT01112670PHASE4COMPLETEDThe Role of P-glycoprotein in Sitagliptin Clinical Pharmacology
NCT01131182PHASE4COMPLETEDStudy of Sitagliptin Treatment in Patients With Type 2 Diabetes During Ramadan (0431-263)
NCT01186562PHASE4COMPLETEDSitagliptin Therapy to Improve Outcomes After Islet Autotransplant
NCT01193296PHASE4COMPLETEDGlycemic Holter Study (Continuous Glucose Monitoring) -

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 5 clinical and 37 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

28 molecules share ≥1 primary target. Top 28 by shared-target count:

MoleculeSourceStatusShared targets
ALOGLIPTINChEMBL + PubChemPhase 4 (approved)DPP4
LINAGLIPTINChEMBL + PubChemPhase 4 (approved)DPP4
SAXAGLIPTINChEMBL + PubChemPhase 4 (approved)DPP4
ANAGLIPTINChEMBLPhase 4 (approved)DPP4
EVOGLIPTINChEMBLPhase 4 (approved)DPP4
GEMIFLOXACINChEMBLPhase 4 (approved)DPP4
GOSOGLIPTINChEMBLPhase 4 (approved)DPP4
METFORMINChEMBLPhase 4 (approved)DPP4
OMARIGLIPTINChEMBLPhase 4 (approved)DPP4
TENELIGLIPTINChEMBLPhase 4 (approved)DPP4
TRELAGLIPTINChEMBLPhase 4 (approved)DPP4
VIDARABINEChEMBLPhase 4 (approved)DPP4
VILDAGLIPTINChEMBLPhase 4 (approved)DPP4
CAFFEIC ACIDChEMBLPhase 3DPP4
DBPR-108ChEMBLPhase 3DPP4
DUTOGLIPTINChEMBLPhase 3DPP4
EPIGALOCATECHIN GALLATEChEMBLPhase 3DPP4
QUERCETINChEMBLPhase 3DPP4
RESVERATROLChEMBLPhase 3DPP4
RETAGLIPTINChEMBLPhase 3DPP4
TALABOSTATChEMBLPhase 3DPP4
CARMEGLIPTINChEMBLPhase 2DPP4
COFROGLIPTINChEMBLPhase 2DPP4
FLAVONEChEMBLPhase 2DPP4
GALLIC ACIDChEMBLPhase 2DPP4
GENISTEINChEMBLPhase 2DPP4
LUTEOLINChEMBLPhase 2DPP4
CarfilzomibPubChemApprovedDPP4

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot