Compound Detail

CHEMBL221959

TOFACITINIB

💊 Approved Drug

Enter ChEMBL ID:

Free Research Context This compound will appear in recent viewed items on the research home for this browser.

Research home View demo workspace

💊 Approved Drug

C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)c1ncnc2[nH]ccc12

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL221959
Name	TOFACITINIB
Phase	Approved
Structure Type	MOL
InChI Key	UJLAWZDWDVHWOW-YPMHNXCESA-N
Therapeutic	✓ Yes

Known Names

550 CP 690550 CP- 690 550 CP-690 Cp-690 free base CP-690,550 CP-690,550 FREE BASE CP-690-550 CP-690550 CP-690550 FREE BASE CP690,550 CP690550 +1 more

Targets

511

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Molecular Properties

312.4

MW (Da)

1.54

ALogP

HBA

HBD

88.9

PSA (Å²)

0.93

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2012
Availability	Prescription
Chirality	Single Enantiomer

Routes of Administration

Oral

Flags

Black Box Warning Natural Product Chemical Probe

USAN Stem	-tinib
USAN Year	2010

Extended Properties

Molecular Formula	C16H20N6O
MW	312.38
Aromatic Rings	2
Heavy Atoms	23
NP-Likeness	-1.14

Indications

Arthritis, Juvenile Arthritis, Psoriatic Arthritis, Rheumatoid Colitis, Ulcerative Glioblastoma Polymyalgia Rheumatica Psoriasis Psoriasis Severe Acute Respiratory Syndrome Spondylitis, Ankylosing Takayasu Arteritis Alopecia Areata Colitis Crohn Disease Down Syndrome Dry Eye Syndromes Granuloma, Lethal Midline Leishmaniasis, Cutaneous Myocarditis Myositis

ATC Classification

L04AF01

tofacitinib

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: IMMUNOSUPPRESSANTS

Activity Summary

IC50 386 meas. best 9.62

Kd 84 meas. best 9.8

Ki 26 meas. best 9.7

EC50 15 meas. best 7.55

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Tyrosine-protein kinase JAK3 CHEMBL2148	Kd	9.8	9.0675	0.2	4
Tyrosine-protein kinase JAK3 CHEMBL2148	Ki	9.7	9.4486	0.2	7
Tyrosine-protein kinase JAK3 CHEMBL2148	IC50	9.62	8.4034	0.2	70
Non-receptor tyrosine-protein kinase TYK2 CHEMBL3553	IC50	9.4	7.3073	0.4	33
Tyrosine-protein kinase JAK2 CHEMBL2971	IC50	9.3	7.6818	0.5	85
Tyrosine-protein kinase JAK1 CHEMBL2835	IC50	9.3	8.2389	0.5	64
Tyrosine-protein kinase JAK2 CHEMBL2971	Kd	9.24	8.645	0.6	4
Tyrosine-protein kinase JAK1 CHEMBL2835	Ki	9.19	9.1614	0.6	7
Tyrosine-protein kinase JAK2 CHEMBL2971	Ki	9.15	9.075	0.7	6
Unchecked CHEMBL612545	IC50	9.0	6.971	1.0	20
Tyrosine-protein kinase JAK1 CHEMBL2835	Kd	8.8	8.785	1.6	2
T-cell CHEMBL614309	IC50	8.7	8.1533	2.0	3
Non-receptor tyrosine-protein kinase TYK2 CHEMBL3553	Ki	8.36	8.216	4.4	5
Unchecked CHEMBL612545	Ki	8.36	8.36	4.4	1
Serine/threonine-protein kinase DCLK3 CHEMBL6123	Kd	8.35	8.2067	4.5	3
Non-receptor tyrosine-protein kinase TYK2 CHEMBL3553	Kd	8.32	6.835	4.8	4
JAK3/JAK1 CHEMBL3038491	IC50	8.17	7.4465	6.7	20
NON-PROTEIN TARGET CHEMBL3879801	IC50	7.96	7.1386	11.0	7
JAK1/TYK2 CHEMBL3301391	IC50	7.58	7.0838	26.0	13
JAK3/JAK1 CHEMBL3038491	EC50	7.55	7.55	28.0	1
Janus Kinase (JAK) CHEMBL2363062	IC50	7.41	5.4629	39.0	7
PBMC CHEMBL613107	IC50	7.41	7.41	39.0	1
HeLa CHEMBL399	IC50	7.4	7.4	40.0	1
Tyrosine-protein kinase JAK1/JAK3 CHEMBL3885650	IC50	7.38	7.34	42.0	2
Tyrosine-protein kinase JAK1 CHEMBL2835	EC50	7.37	7.298	43.0	5
Tyrosine-protein kinase JAK3 CHEMBL5250	IC50	7.32	6.445	48.0	6
JAK2/JAK1 CHEMBL3038492	IC50	7.29	6.8564	51.0	11
Serine/threonine-protein kinase N1 CHEMBL3384	Kd	7.24	6.8525	58.0	4
Human immunodeficiency virus 2 CHEMBL380	EC50	7.16	7.16	70.0	1
JAK1/JAK2/TYK2 CHEMBL3301390	IC50	7.12	6.72	75.4	3
TF-1 CHEMBL612552	IC50	7.1	6.396	80.0	5
Tyrosine-protein kinase JAK2 CHEMBL2971	EC50	7.03	6.9575	93.0	4
A549 CHEMBL392	IC50	7.0	7.0	100.0	1
HepG2 CHEMBL395	IC50	6.96	6.96	110.0	1
JAK1/TYK2 CHEMBL4523618	IC50	6.95	6.95	112.0	1
Non-receptor tyrosine-protein kinase TNK1 CHEMBL5334	Kd	6.92	6.2675	120.0	4
U-937 CHEMBL612794	IC50	6.91	6.91	122.4	1
Whole blood CHEMBL2367373	IC50	6.86	6.86	139.0	1
JAK2/JAK1 CHEMBL3038492	EC50	6.77	6.77	170.0	1
BaF3 CHEMBL614524	IC50	6.75	5.9183	177.3	6
Tyrosine-protein kinase JAK1/JAK2 CHEMBL3885649	IC50	6.75	6.74	180.0	2
Human immunodeficiency virus 1 CHEMBL378	EC50	6.7	6.7	200.0	1
JAK2/TYK2 CHEMBL3301392	IC50	6.64	6.5433	229.0	3
NUAK family SNF1-like kinase 2 CHEMBL5698	Kd	6.62	6.46	240.0	3
Tyrosine-protein kinase JAK1 CHEMBL2968	IC50	6.59	6.59	258.0	1
U-251 CHEMBL615022	IC50	6.48	6.48	330.0	1
Tyrosine-protein kinase Lck CHEMBL258	IC50	6.47	5.7633	340.0	3
Tyrosine-protein kinase JAK2 CHEMBL1649049	IC50	6.42	5.8233	384.0	3
Rho-associated protein kinase 2 CHEMBL2973	Kd	6.38	5.955	420.0	2
Dual specificity mitogen-activated protein kinase kinase 1 CHEMBL3587	Kd	6.37	6.37	429.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	656.0	ng.hr.mL-1	Rattus norvegicus
AUC	2800.0	ng.hr.mL-1	Rattus norvegicus
AUC	2300.0	ng.hr.mL-1	Canis lupus familiaris
AUC	1740.0	ng.hr.mL-1	Rattus norvegicus
AUC	1735.0	ng.hr.mL-1	Rattus norvegicus
AUC	1551.9	ng.hr.mL-1	Rattus norvegicus
AUC	1205.0	ng.hr.mL-1	Rattus norvegicus
AUC	1230.0	ng.hr.mL-1	Rattus norvegicus
AUC	1205.0	ng.hr.mL-1	Rattus norvegicus
CL	18.0	mL.min-1.kg-1	Macaca fascicularis
CL	19.0	mL.min-1.kg-1	Canis lupus familiaris
CL	62.0	mL.min-1.kg-1	Rattus norvegicus
CL	10.0	mL.min-1.g-1	Homo sapiens
CL	43.0	mL.min-1.kg-1	Rattus norvegicus
CL	8.0	mL.min-1.g-1	Homo sapiens
CL	96.83	mL.min-1.kg-1	Rattus norvegicus
CL	8.0	mL.min-1.kg-1	Homo sapiens
CL	63.0	mL.min-1.kg-1	Rattus norvegicus
CL	25.0	mL.min-1.g-1	Homo sapiens
CL	25.0	mL.min-1.g-1	Homo sapiens
Cmax	1414.94	nM	Rattus norvegicus
Cmax	2528.97	nM	Macaca fascicularis
Cmax	3265.25	nM	Canis lupus familiaris
Cmax	1700.0	nM	Rattus norvegicus
Cmax	7682.95	nM	Rattus norvegicus
Cmax	6562.52	nM	Rattus norvegicus
F	27.0	%	Rattus norvegicus
F	48.0	%	Macaca fascicularis
F	78.0	%	Canis lupus familiaris
F	87.0	%	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Tyrosine-protein kinase JAK3	Kd	=	0.16	nM	9.8	Binding constant for JAK3(JH1domain-catalytic) kinase domain	22037378
Tyrosine-protein kinase JAK3	Ki	=	0.2	nM	9.7	Inhibition of JAK3 (unknown origin)	33481605
Tyrosine-protein kinase JAK3	Ki	=	0.24	nM	9.62	Inhibition of recombinant human GST-tagged JAK3 (781 to 1124 residues) expressed...	20701804
Tyrosine-protein kinase JAK3	Ki	=	0.24	nM	9.62	Inhibition of human recombinant JAK3 kinase domain using FITC-KGGEEEEYFELVKK as ...	22591402
Tyrosine-protein kinase JAK3	IC50	=	0.24	nM	9.62	Inhibition of JAK3 (unknown origin) preincubated for 20 mins followed by [33P]-A...	30460842
Tyrosine-protein kinase JAK3	IC50	=	0.241	nM	9.62	JAK Inhibition Activity Assays: Reagents used in JAK inhibition assay: Base Reac...	-
Tyrosine-protein kinase JAK3	IC50	=	0.292	nM	9.54	Inhibition of JAK3 (unknown origin) in presence of ATP by radiometric assay	27840070
Tyrosine-protein kinase JAK3	IC50	=	0.29	nM	9.54	Inhibition of human JAK3 using GEEEEYFELVKKKK as substrate in presence of 10 uM ...	29852068
Tyrosine-protein kinase JAK3	IC50	=	0.34	nM	9.47	Inhibition of GST-tagged recombinant human JAK3 catalytic domain expressed in ba...	29156136
Tyrosine-protein kinase JAK3	IC50	=	0.35	nM	9.46	Inhibition of JAK3 (unknown origin)	26927423
Tyrosine-protein kinase JAK3	IC50	=	0.4	nM	9.4	Inhibition of JAK3 (unknown origin)	38359535
Non-receptor tyrosine-protein kinase TYK2	IC50	=	0.4	nM	9.4	Inhibition of TYK2 (unknown origin)	37057760
Tyrosine-protein kinase JAK3	Ki	=	0.4	nM	9.4	Inhibition of JAK3 (unknown origin) using Leu-Pro-Leu-Asp-Lys-Asp-Tyr-Tyr-Val-Va...	23659214
Tyrosine-protein kinase JAK3	Ki	=	0.4	nM	9.4	Inhibition of human GST-fused JAK3 catalytic domain expressed in baculovirus-inf...	23668484
Tyrosine-protein kinase JAK3	Ki	=	0.4	nM	9.4	Inhibition of JAK3	22591402
Tyrosine-protein kinase JAK2	IC50	=	0.5	nM	9.3	Inhibition of human JAK2 using TK-substrate-biotin preincubated for 5 mins follo...	30853331
Tyrosine-protein kinase JAK1	IC50	=	0.5	nM	9.3	Inhibition of human JAK1 using poly[Glu:Tyr] (4:1) as substrate in presence of 1...	29852068
Tyrosine-protein kinase JAK1	IC50	=	0.496	nM	9.3	Inhibition of JAK1 (unknown origin) in presence of ATP by radiometric assay	27840070
Tyrosine-protein kinase JAK2	Kd	=	0.58	nM	9.24	Binding constant for JAK2(JH1domain-catalytic) kinase domain	22037378
Tyrosine-protein kinase JAK2	IC50	=	0.6	nM	9.22	Inhibition of human recombinant JAK2	25369270

Literature References

PubMed	DOI	Target Context	# Activities
14593182	10.1126/science.1087061	Cynomolgus monkey	21
22037378	10.1038/nbt.1990	Tyrosine-protein kinase ABL1	15
14593182	10.1126/science.1087061	Mus musculus	15
24417533	10.1021/jm401490p	Homo sapiens	13
22037378	10.1038/nbt.1990	Epidermal growth factor receptor	12
27840070	10.1016/j.chembiol.2016.10.008	Unchecked	11
37870434	10.1021/acs.jmedchem.3c01365	Mus musculus	10
22037378	10.1038/nbt.1990	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
20701804	10.1186/1476-9255-7-41	Unchecked	10
14593182	10.1126/science.1087061	NON-PROTEIN TARGET	10
20701804	10.1186/1476-9255-7-41	Rattus norvegicus	10
18183025	10.1038/nbt1358	Epidermal growth factor receptor	10
37738648	10.1021/acs.jmedchem.3c00554	Unchecked	9
26254279	10.18632/oncotarget.4214	Janus Kinase (JAK)	9
30926315	10.1016/j.bmc.2019.03.048	ADMET	8
38359535	10.1016/j.ejmech.2024.116210	Unchecked	8
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8
29452839	10.1016/j.bmc.2018.01.021	Mus musculus	8
30113844	10.1021/acs.jmedchem.8b00917	JAK2/JAK1	8
14593182	10.1126/science.1087061	Unchecked	8

Data from ChEMBL 36 via Core Engine