Drug Information

Drug (ID: DG01090) and It's Reported Resistant Information

• Name: Sitagliptin
• Synonyms: Sitagliptin; 486460-32-6; Januvia; Xelevia; MK-0431; (R)-3-AMINO-1-(3-(TRIFLUOROMETHYL)-5,6-DIHYDRO-[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL)-4-(2,4,5-TRIFLUOROPHENYL)BUTAN-1-ONE; UNII-QFP0P1DV7Z; Tesavel; LEZ763; QFP0P1DV7Z; (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; (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; (2R)-4-OXO-4-[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]-1-(2,4,5-TRIFLUOROPHENYL)BUTAN-2-AMINE; 790712-60-6; CHEBI:40237; Sitagliptan; MK0431; Sitagliptin (Prop.INN); sitagliptina; sitagliptine; sitagliptinum; SR-05000001748; HSDB 7516; LEZ 763; (2R)-4-OXO-4-[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]-1-(2,4,5-TRIFLUOROPHENYL)BUTAN-2-A MINE; Sitagliptin (13); (3R)-3-Amino-1-[3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one; Sitagliptin; MK0431; 1169707-31-6; EC 690-730-1; CHEMBL1422; SCHEMBL17783; BSPBio_002262; Triazolopiperazine Analogue 1; (3R)-3-amino-1-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)butan-1-one; MLS006011959; Sitagliptin [USAN:INN:BAN]; GTPL6286; BDBM11162; C16H15F6N5O; AMY6930; DTXSID70197572; LEZ-763; 1x70; HMS2093F20; ACT02665; EX-A2816; Sitagliptin (Metformin,MK-0431); WHO 8692; ZINC1489478; MFCD09838015; NSC813215; AKOS015888724; CCG-268731; DB01261; MCULE-2101761133; NSC-813215; NCGC00178734-03; NCGC00178734-06; NCGC00178734-13; 7-((3R)-3-Amino-1-oxo-4-(2,4,5-trifluorophenyl)buyl)-5,6,7,8-tetrahydro-3-trifluoromethyl)-1,4-triazolo(4,3-a); AS-19118; HY-13749; SMR002546724; SBI-0206871.P001; Sitagliptin 100 microg/mL in Acetonitrile; S5079; X4663; A14377; A25516; D08516; AB01563393_01; AR-270/43507782; Q419832; Q-101366; Q-201711; SR-05000001748-1; BRD-K19416115-001-01-2; BRD-K19416115-001-03-8; Z1541638523; (1R)-3-oxo-3-[3-(trifluoroethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorobenzyl)propylamine; (2r)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a] pyrazin-7(8h)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine; (2r)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8h)-yl]-1-(2,4,5-trifluorophenyl)butan-2-a; (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-alpha]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine; (3r)-3-amino-1-[3-(trifluoromethyl)-5,6,7,8-tetrahydro-5h-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one; (3R)-3-amino-1-[3-(trifluoromethyl)-5H,6H,7H,8H-[1,2,4]triazolo[3,4-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one hydrochloride; (R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine; 1,2,4-Triazolo(4,3-a)pyrazine, 7-((3R)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl)-5,6,7,8-tetrahydor-3-(trifluoromethyl)-; 1,2,4-Triazolo[4,3-a]pyrazine,7-[(3R)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-; 3-oxo-1-(2,4,5-trifluorobenzyl)-3-(3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)propylamine; 7-[(3r)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazine
• Indication:
  In total 4 Indication(s)
  Type-2 diabetes [ICD-11: 5A11]; Approved; [1]
  Type-2 diabetes [ICD-11: 5A11]; Phase 3; [1]
  Type-2 diabetes [ICD-11: 5A11]; Phase 3; [1]
  Peripheral arterial disease [ICD-11: BD4Z]; Phase 1; [1]
• Formula: C16H15F6N5O
• IsoSMILES: C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)C[C@@H](CC3=CC(=C(C=C3F)F)F)N
• 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
• InChIKey: MFFMDFFZMYYVKS-SECBINFHSA-N
• PubChem CID: 4369359
• TTD Drug ID: D05RTM
• VARIDT ID: DR00254
• INTEDE ID: DR1490
• DrugBank ID: DB01261

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-05: Endocrine/nutritional/metabolic diseases

Insulin-resistance syndrome [ICD-11: 5A44]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Dipeptidyl peptidase 4 (DPP4) [1]

• Sensitive Disease: Insulin-resistance syndrome [ICD-11: 5A44.0]
• Molecule Alteration: Function; Inhibition
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that is currently indicated as an adjunctive treatment to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (DM). Sitagliptin is used to help mitigate insulin resistance after burn injury.

ICD-08: Nervous system diseases

Epilepsy [ICD-11: 8A60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Protein kinase C gamma type (PRKCG) [2]

• Sensitive Disease: Epilepsy [ICD-11: 8A60.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Wistar rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Protein kinase assay; RT-qPCR
• Experiment for Drug Resistance: Experimental Animal Model
• Mechanism Description: Mechanistic insights revealed sitagliptin's ability to modulate the seizure grade and first myoclonic jerk latency via oxidative stress markers, like reduced glutathione and glutathione peroxidase emphasizing its antioxidative role in epilepsy. Additionally, it demonstrated anti-inflammatory effects by significantly reducing proinflammatory markers interleukin-1beta and interleukin-6. The modulation of key genes of the long-term potentiation pathway, particularly protein kinase C-gamma and metabotropic glutamate receptor 5, was evident through mRNA expression levels. Finally, sitagliptin showed potential neuroprotective properties, limiting pentylenetetrazolium-induced neuronal loss in the hippocampal region. Collectively, our findings suggest sitagliptin's multidimensional therapeutic potential for drug-resistant epilepsy specifically via a long-term potentiation pathway by inhibiting protein kinase C-gamma.

References

• Ref 1: Evaluation of the use of sitagliptin for insulin resistance in burn patients .Int J Burns Trauma. 2020 Oct 15;10(5):237-245. eCollection 2020.
• Ref 2: Unlocking the Therapeutic Potential: Sitagliptin's Multifaceted Approach in Drug-Resistant Epilepsy through a Novel Mechanism Inhibiting Protein Kinase C-gamma and a Long-Term Potentiation Pathway. ACS Pharmacol Transl Sci. 2024 May 14;7(6):1856-1863.