Details of the Drug

General Information of Drug (ID: DMGDKXN)

Drug Name

Sitagliptin

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
Type-2 diabetes	5A11	Approved	[1], [2], [3], [4]
Peripheral arterial disease	BD4Z	Phase 1/2	[5]

Therapeutic Class

Hypoglycemic Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

407.31

Topological Polar Surface Area (xlogp)

0.7

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [6]
Bioavailability: 87% of drug becomes completely available to its intended biological destination(s) [7]
Clearance: The clearance of drug is 350 mL/min [8]
Elimination: 87% of the dose is eliminated in the urine and 13% in the feces [9]
Half-life: The concentration or amount of drug in body reduced by one-half in 12.4 hours [9]
Metabolism: The drug is metabolized via the cytochrome p450(CYP)3A4 and to a lesser extent by CYP2C8 [10]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.35072 micromolar/kg/day [11]
Unbound Fraction: The unbound fraction of drug in plasma is 0.62% [12]
Vd: The volume of distribution (Vd) of drug is 198 L [13]

Chemical Identifiers

Formula: C16H15F6N5O
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
Canonical SMILES: C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)C[C@@H](CC3=CC(=C(C=C3F)F)F)N
InChI: 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

Cross-matching ID

PubChem CID: 4369359
ChEBI ID: CHEBI:40237
CAS Number: 486460-32-6
DrugBank ID: DB01261
TTD ID: D0U2JP
VARIDT ID: DR00254
INTEDE ID: DR1490
ACDINA ID: D00628

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dipeptidyl peptidase 4 (DPP-4)	TTDIGC1	DPP4_HUMAN	Inhibitor	[14], [15], [16], [17]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[18]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[19]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[20]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[21]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[21]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Type-2 diabetes

ICD Disease Classification

5A11

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Dipeptidyl peptidase 4 (DPP-4)	DTT	DPP4	9.54E-01	-0.27	-1.85
Organic anion transporter 3 (SLC22A8)	DTP	OAT3	6.49E-01	3.37E-03	6.66E-02
P-glycoprotein 1 (ABCB1)	DTP	P-GP	2.30E-01	3.06E-01	7.43E-01
Organic cation transporter 1 (SLC22A1)	DTP	SLC22A1	1.46E-01	2.34E-01	7.18E-01
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	4.79E-01	-1.88E-02	-1.73E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	2.76E-01	-4.64E-01	-9.16E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Sitagliptin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Moderate	Increased metabolism of Sitagliptin caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[74]
Erdafitinib	DMI782S	Moderate	Decreased clearance of Sitagliptin due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[75]
Tucatinib	DMBESUA	Moderate	Decreased clearance of Sitagliptin due to the transporter inhibition by Tucatinib.	Breast cancer [2C60-2C6Y]	[76]
BMS-201038	DMQTAGO	Moderate	Decreased clearance of Sitagliptin due to the transporter inhibition by BMS-201038.	Hyper-lipoproteinaemia [5C80]	[77]
Ibrutinib	DMHZCPO	Moderate	Decreased clearance of Sitagliptin due to the transporter inhibition by Ibrutinib.	Mature B-cell lymphoma [2A85]	[74]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Sitagliptin caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[78]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of Sitagliptin due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[79]
Rolapitant	DM8XP26	Moderate	Decreased clearance of Sitagliptin due to the transporter inhibition by Rolapitant.	Nausea/vomiting [MD90]	[80]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Sitagliptin caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[81]
Fostamatinib	DM6AUHV	Moderate	Decreased clearance of Sitagliptin due to the transporter inhibition by Fostamatinib.	Thrombocytopenia [3B64]	[82]
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⏷ Show the Full List of 10 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Sodium stearyl fumarate	E00545	23665634	lubricant
Calcium hydrogenphosphate	E00294	24441	Diluent
Carmellose sodium	E00625	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Magnesium stearate	E00208	11177	lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
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⏷ Show the Full List of 9 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Sitagliptin 50 mg tablet	50 mg	Oral Tablet	Oral
Sitagliptin 100 mg tablet	100 mg	Oral Tablet	Oral
Sitagliptin 25 mg tablet	25 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

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