Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMGDKXN)

Drug Name
Sitagliptin Drug Info
Synonyms
486460-32-6; Januvia; Xelevia; Sitagliptan; MK-0431; UNII-QFP0P1DV7Z; Tesavel; 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; (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; CHEBI:40237; (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; Janumet; Sitagliptin phosphate; Januvia (TN); Sitagliptin (PropINN); Januvia (merck & Co); (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; (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; (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; Sitagliptin/atovastatin
Indication
Disease Entry ICD 11 Status REF
Cystic fibrosis CA25 Approved [1]
Non-insulin dependent diabetes 5A11 Approved [1]
Renal hypoplasia Approved [1]
Type-2 diabetes 5A11 Approved [2]
Peripheral arterial disease BD4Z Phase 1/2 [3]
Therapeutic Class
Hypoglycemic Agents
Cross-matching ID
PubChem CID
4369359
ChEBI ID
CHEBI:40237
CAS Number
CAS 486460-32-6
TTD Drug ID
DMGDKXN
VARIDT Drug ID
DR00254
INTEDE Drug ID
DR1490
ACDINA Drug ID
D00628

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DTP
DME
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Dipeptidyl peptidase 4 (DPP-4)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Saxagliptin DMGXENV Type-2 diabetes 5A11 Approved [9]
Alogliptin DM8WI3R Type-2 diabetes 5A11 Approved [10]
Linagliptin DMWFJTR Non-insulin dependent diabetes 5A11 Approved [11]
Vildagliptin DMYN59P Type-2 diabetes 5A11 Approved [12]
Dapagliflozin Propanediol; Saxagliptin Hydrochloride DM34TXO Type-2 diabetes 5A11 Approved [13]
Anagliptin DMJXIC9 Type-2 diabetes 5A11 Approved [14]
SaxaDapa FDC DMAPRWV Diabetic complication 5A2Y Phase 3 [15]
LC-150444 DM09RKB Type-2 diabetes 5A11 Phase 3 [16]
Dutogliptin DMM5VTA Type-2 diabetes 5A11 Phase 3 [17]
MK-3102 DM3PSUF Type-2 diabetes 5A11 Phase 3 [18]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Transported By P-glycoprotein 1 (ABCB1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Amoxicillin DMUYNEI Acute otitis media AB00 Approved [19]
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [20]
Methotrexate DM2TEOL Anterior urethra cancer Approved [21]
Folic Acid DMEMBJC Colorectal carcinoma Approved [22]
Fluorouracil DMUM7HZ Adenocarcinoma 2D40 Approved [21]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [21]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [23]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [21]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [24]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [25]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Transported By Organic cation transporter 1 (SLC22A1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [26]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [27]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [28]
Oxaliplatin DMQNWRD Adenocarcinoma 2D40 Approved [29]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [19]
Verapamil DMA7PEW Angina pectoris BA40 Approved [30]
Sorafenib DMS8IFC Adenocarcinoma 2D40 Approved [31]
Quinine DMSWYF5 Malaria 1F40-1F45 Approved [32]
Dopamine DMPGUCF Acromegaly 5A60.0 Approved [33]
Propranolol DM79NTF Angina pectoris BA40 Approved [34]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Transported By Organic anion transporter 3 (SLC22A8)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Methotrexate DM2TEOL Anterior urethra cancer Approved [35]
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [36]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [37]
Prasterone DM67VKL Chronic obstructive pulmonary disease CA22 Approved [38]
Pravastatin DM6A0X7 Adult acute monocytic leukemia Approved [39]
L-Tryptophan DMIBH7M Depression 6A70-6A7Z Approved [40]
Mercaptopurine DMTM2IK Acute lymphoblastic leukaemia 2A85 Approved [41]
PITAVASTATIN CALCIUM DM1UJO0 Dyslipidemia 5C80-5C81 Approved [42]
Rosuvastatin DMMIQ7G Arteriosclerosis BD40 Approved [43]
Cilostazol DMZMSCT Intermittent claudication BD40.00 Approved [44]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [45]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [46]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [47]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [48]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [49]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [50]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [51]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [52]
Prasterone DM67VKL Chronic obstructive pulmonary disease CA22 Approved [46]
Verapamil DMA7PEW Angina pectoris BA40 Approved [53]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By Cytochrome P450 2C8 (CYP2C8)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Fluorouracil DMUM7HZ Adenocarcinoma 2D40 Approved [54]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [55]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [55]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [56]
Verapamil DMA7PEW Angina pectoris BA40 Approved [57]
Diclofenac DMPIHLS Chronic renal failure GB61.Z Approved [58]
Sorafenib DMS8IFC Adenocarcinoma 2D40 Approved [59]
Quinine DMSWYF5 Malaria 1F40-1F45 Approved [55]
Mycophenolate mofetil DMPQAGE Hepatosplenic T-cell lymphoma Approved [60]
Propofol DMB4OLE Anaesthesia 9A78.6 Approved [61]
⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Dipeptidyl peptidase 4 (DPP-4) TTDIGC1 DPP4_HUMAN Inhibitor [4]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [5]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [6]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) Main DME DE4LYSA CP3A4_HUMAN Substrate [8]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [8]

References

1 Sitagliptin FDA Label
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6286).
3 ClinicalTrials.gov (NCT01619332) Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763. U.S. National Institutes of Health.
4 Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol Ther. 2009 Oct;124(1):113-38.
5 265 effect of dietary cholesterol on gallbladder bile lithogenicity and gene expression in the enterohepatic axis of non-obese gallstone and control women. Journal of Hepatology, 2009, 50(09):S105-S106.
6 Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein. J Pharmacol Exp Ther. 2007 May;321(2):673-83.
7 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
8 Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58.
9 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
10 Clinical pipeline report, company report or official report of Takeda (2009).
11 Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
12 Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes. Curr Drug Targets. 2009 Jan;10(1):71-87.
13 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
14 Diabetes Treatment. Diabetes Care. 2009 March; 32(3): e25-e30.
15 Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for type 2 diabetes. Cardiol Rev. 2010 Jul-Aug;18(4):213-7.
16 Clinical pipeline report, company report or official report of ShangHai APIs Chemical.
17 Dutogliptin, a selective DPP4 inhibitor, improves glycaemic control in patients with type 2 diabetes: a 12-week, double-blind, randomized, placebo-controlled, multicentre trial. Diabetes Obes Metab. 2010 Apr;12(4):348-55.
18 Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes. J Med Chem. 2014 Apr 24;57(8):3205-12.
19 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
20 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
21 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
22 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
23 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
24 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
25 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
26 Are organic cation transporters capable of transporting prostaglandins? Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):125-30.
27 Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family). J Pharmacol Exp Ther. 2006 Nov;319(2):879-86.
28 Pharmacologic markers and predictors of responses to imatinib therapy in patients with chronic myeloid leukemia. Leuk Lymphoma. 2008 Apr;49(4):639-42.
29 Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57.
30 Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
31 Upregulation of histone acetylation reverses organic anion transporter 2 repression and enhances 5-fluorouracil sensitivity in hepatocellular carcinoma
32 Comparison of type I and type II organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5.
33 Organic cation transporters and their pharmacokinetic and pharmacodynamic consequences. Drug Metab Pharmacokinet. 2008;23(4):243-53.
34 Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the Retinal Delivery of Neuroprotectants. Biol Pharm Bull. 2017;40(8):1139-1145.
35 Methotrexate-loxoprofen interaction: involvement of human organic anion transporters hOAT1 and hOAT3. Drug Metab Pharmacokinet. 2004 Oct;19(5):369-74.
36 Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
37 Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
38 Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86.
39 Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments. Drug Metab Dispos. 2011 Jun;39(6):1031-8.
40 Murine renal organic anion transporters mOAT1 and mOAT3 facilitate the transport of neuroactive tryptophan metabolites. Am J Physiol Cell Physiol. 2005 Nov;289(5):C1075-84.
41 Organic anion transporter 3 is involved in the brain-to-blood efflux transport of thiopurine nucleobase analogs. J Neurochem. 2004 Aug;90(4):931-41.
42 Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
43 The contribution of organic anion transporters OAT1 and OAT3 to the renal uptake of rosuvastatin. J Pharmacol Exp Ther. 2007 Sep;322(3):1221-7.
44 Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat. Drug Metab Dispos. 2014 Jun;42(6):996-1007.
45 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
46 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
47 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
48 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
49 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
50 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
51 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
52 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
53 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
54 Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
55 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
56 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
57 Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
58 Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
59 Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
60 PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
61 Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.