Details of the Drug

General Information of Drug (ID: DMBS370)

Drug Name

Tofacitinib

Synonyms

Tasocitinib; 477600-75-2; 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile; CP-690550; CP 690550; racemic-tofacitinib; 1259404-17-5; tofacitinibum; CP-690,550; UNII-87LA6FU830; 3-((3R,4R)-rel-4-Methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile; 3-{(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}-3-oxopropanenitrile; Tofacitinib (CP-690550,Tasocitinib); CHEMBL221959; CHEBI:71200; Xeljanz (TN)

Indication

Disease Entry	ICD 11	Status	REF
Rheumatoid arthritis	FA20	Approved	[1]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[2]
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Affected Organisms

Humans and other mammals

ATC Code

L04AA29: Tofacitinib

L04AA: Selective immunosuppressants

L04A: IMMUNOSUPPRESSANTS

L04: IMMUNOSUPPRESSANTS

L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

312.37

Logarithm of the Partition Coefficient (xlogp)

1.5

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Clearance: The drug present in the plasma can be removed from the body at the rate of 5.88 mL/min/kg [3]
Unbound Fraction: The unbound fraction of drug in plasma is 0.6% [3]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.24 L/kg [3]

Chemical Identifiers

Formula: C16H20N6O
IUPAC Name: 3-[(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile
Canonical SMILES: C[C@@H]1CCN(C[C@@H]1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N
InChI: InChI=1S/C16H20N6O/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-20-16/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20)/t11-,13+/m1/s1
InChIKey: UJLAWZDWDVHWOW-YPMHNXCESA-N

Cross-matching ID

PubChem CID: 9926791
ChEBI ID: CHEBI:71200
CAS Number: 477600-75-2
UNII: 87LA6FU830
DrugBank ID: DB08895
TTD ID: D0EG1I
INTEDE ID: DR1610
ACDINA ID: D00683

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Janus kinase 3 (JAK-3)	TTT7PJU	JAK3_HUMAN	Modulator	[4]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[5]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[5]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
2'-5'-oligoadenylate synthase 1 (OAS1)	OT8ZLOCY	OAS1_HUMAN	Gene/Protein Processing	[6]
2'-5'-oligoadenylate synthase 2 (OAS2)	OT64CCTM	OAS2_HUMAN	Gene/Protein Processing	[6]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Regulation of Drug Effects	[7]
AMP deaminase 2 (AMPD2)	OTBS30JU	AMPD2_HUMAN	Gene/Protein Processing	[8]
Bone marrow stromal antigen 2 (BST2)	OTU4LCJV	BST2_HUMAN	Gene/Protein Processing	[6]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Gene/Protein Processing	[9]
C-X-C motif chemokine 10 (CXCL10)	OTTLQ6S0	CXL10_HUMAN	Gene/Protein Processing	[10]
C-X-C motif chemokine 11 (CXCL11)	OT353XE3	CXL11_HUMAN	Gene/Protein Processing	[10]
C-X-C motif chemokine 13 (CXCL13)	OT2AT4N8	CXL13_HUMAN	Gene/Protein Processing	[9]
C-X-C motif chemokine 9 (CXCL9)	OTMFVZKZ	CXCL9_HUMAN	Gene/Protein Processing	[10]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Rheumatoid arthritis

ICD Disease Classification

FA20

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Janus kinase 3 (JAK-3)	DTT	JAK3	4.94E-03	0.28	1.41
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	3.82E-03	1.37E-01	1.05E+00
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	3.09E-05	-6.05E-01	-3.19E+00
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	2.51E-01	8.39E-02	5.00E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.93E-04	-6.16E-01	-2.64E+00

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Tofacitinib caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[11]
Arn-509	DMT81LZ	Major	Increased metabolism of Tofacitinib caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[11]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Tofacitinib caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[11]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Tofacitinib caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[11]
Tucatinib	DMBESUA	Major	Decreased metabolism of Tofacitinib caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[11]
Osilodrostat	DMIJC9X	Moderate	Decreased metabolism of Tofacitinib caused by Osilodrostat mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[12]
Lumacaftor	DMCLWDJ	Major	Increased metabolism of Tofacitinib caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[11]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Tofacitinib caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[11]
Stiripentol	DMMSDOY	Moderate	Decreased metabolism of Tofacitinib caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[11]
Cobicistat	DM6L4H2	Major	Decreased metabolism of Tofacitinib caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[11]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Tofacitinib caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[11]
Ceritinib	DMB920Z	Major	Decreased metabolism of Tofacitinib caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[11]
Idelalisib	DM602WT	Major	Decreased metabolism of Tofacitinib caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[11]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Tofacitinib caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[11]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Tofacitinib and Siponimod.	Multiple sclerosis [8A40]	[11]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Tofacitinib and Ozanimod.	Multiple sclerosis [8A40]	[13]
Netupitant	DMEKAYI	Moderate	Decreased metabolism of Tofacitinib caused by Netupitant mediated inhibition of CYP450 enzyme.	Nausea/vomiting [MD90]	[11]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Tofacitinib caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[14]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Tofacitinib caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[15]
Enzalutamide	DMGL19D	Major	Increased metabolism of Tofacitinib caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[11]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Tofacitinib when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[16]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Tofacitinib caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[11]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Tofacitinib caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[13]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Tofacitinib caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[11]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Tofacitinib caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[17]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Tofacitinib caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[11]
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⏷ Show the Full List of 26 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
FD&C blue no. 2	E00446	2723854	Colorant
Hydrochloric acid	E00015	313	Acidulant
Lactic acid	E00020	612	Acidulant
Sodium benzoate	E00432	517055	Antimicrobial preservative; lubricant
Sucralose	E00370	71485	Flavoring agent
Food blue 1 aluminum lake	E00512	11979396	Colorant
Ammonia	E00007	222	Alkalizing agent
Carmellose sodium	E00625	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Hexahydric alcohol	E00083	5780	Diluent; Flavoring agent; Humectant; Plasticizing agent
Hydroxypropyl cellulose	E00632	Not Available	Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Hypromellose	E00634	Not Available	Coating agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 3350	E00652	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
Water	E00035	962	Solvent
Xylitol	E00136	6912	Coating agent; Diluent; Emollient; Flavoring agent; Humectant
Colcothar yellow	E00436	518696	Colorant
Haematite red	E00236	14833	Colorant
Sorbitan tristearate	E00516	17800859	Dispersing agent; Emulsifying agent; Solubilizing agent; Surfactant; Suspending agent; Vaccine adjuvant
Cellulose acetate	E00702	Not Available	Coating agent; Modified-release agent; Diluent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
Copovidone	E00693	Not Available	Film/membrane-forming agent; Modified-release agent; Binding agent
Hydroxyethyl cellulose	E00700	Not Available	Coating agent; Suspending agent; Binding agent; Viscosity-controlling agent
Shellac	E00695	Not Available	Coating agent; Film/membrane-forming agent; Microencapsulating agent; Modified-release agent
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⏷ Show the Full List of 29 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Tofacitinib Citrate eq 10mg base tablet	eq 10mg base	Tablet	Oral
Tofacitinib Citrate eq 22mg base extended release tablet	eq 22mg base	Extended Release Tablet	Oral
Tofacitinib Citrate eq 11mg base extended release tablet	eq 11mg base	Extended Release Tablet	Oral
Tofacitinib Citrate eq 5mg base tablet	eq 5mg base	Tablet	Oral
Tofacitinib Citrate eq 1mg base/ml solution	eq 1mg base/ml	Solution	Oral
Tofacitinib 5 mg tablet	5 mg	Oral Tablet	Oral
Tofacitinib 11 mg tablet	11 mg	24 HR Extended Release Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	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: 5677).
2	ClinicalTrials.gov (NCT04332042) TOFAcitinib in SARS-CoV2 Pneumonia. U.S. National Institutes of Health.
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5	The pharmacokinetics, metabolism, and clearance mechanisms of tofacitinib, a janus kinase inhibitor, in humans. Drug Metab Dispos. 2014 Apr;42(4):759-73.
6	White-to-brown metabolic conversion of human adipocytes by JAK inhibition. Nat Cell Biol. 2015 Jan;17(1):57-67. doi: 10.1038/ncb3075. Epub 2014 Dec 8.
7	Elucidating the Mechanism of Tofacitinib Oxidative Decyanation. Drug Metab Lett. 2016;10(2):136-43. doi: 10.2174/1872312810666160427104954.
8	Effects of tofacitinib on nucleic acid metabolism in human articular chondrocytes. Mod Rheumatol. 2015 Jul;25(4):522-7. doi: 10.3109/14397595.2014.995874. Epub 2015 Jan 13.
9	The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis. Ann Rheum Dis. 2015 Jun;74(6):1311-6. doi: 10.1136/annrheumdis-2014-206028. Epub 2014 Nov 14.
10	Regulation of inflammatory responses in tumor necrosis factor-activated and rheumatoid arthritis synovial macrophages by JAK inhibitors. Arthritis Rheum. 2012 Dec;64(12):3856-66. doi: 10.1002/art.37691.
11	Cerner Multum, Inc. "Australian Product Information.".
12	Product Information. Isturisa (osilodrostat). Recordati Rare Diseases Inc, Lebanon, NJ.
13	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
14	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
15	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
16	CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
17	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.