Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C16H20N6O.C6H8O7 |
Molecular Weight | 504.4931 |
Optical Activity | ( + ) |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)CC(O)(CC(O)=O)C(O)=O.C[C@@H]1CCN(C[C@@H]1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N
InChI
InChIKey=SYIKUFDOYJFGBQ-YLAFAASESA-N
InChI=1S/C16H20N6O.C6H8O7/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;7-3(8)1-6(13,5(11)12)2-4(9)10/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20);13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/t11-,13+;/m1./s1
DescriptionCurator's Comment: description was created based on several sources, including
https://www.scribd.com/doc/296556203/A-Review-of-Tofacitinib-Drugs-Pros-and-Cons-of-Pharmaceuticals
Curator's Comment: description was created based on several sources, including
https://www.scribd.com/doc/296556203/A-Review-of-Tofacitinib-Drugs-Pros-and-Cons-of-Pharmaceuticals
Tofacitinib is an orally available inhibitor of Janus kinases (JAK), with immunomodulatory and anti-inflammatory activities. Upon administration, tofacitinib binds to JAK and prevents the activation of the JAK-signal transducers and activators of transcription (STAT) signaling pathway. This may decrease the production of pro-inflammatory cytokines, such as interleukin (IL)-6, -7, -15, -21, interferon-alpha and -beta, and may prevent both an inflammatory response and the inflammation-induced damage caused by certain immunological diseases. JAK kinases are intracellular enzymes involved in signaling pathways affecting hematopoiesis, immunity and inflammation. Tofacitinib was discovered and developed by the National Institutes of Health and Pfizer. Besides rheumatoid arthritis, tofacitinib has also been studied in clinical trials for the prevention of organ transplant rejection, and the treatment of psoriasis and ulcerative colitis. Patients treated with tofacitinib (XELJANZ) are at increased risk for developing serious infections that may lead to hospitalization or death and adverse reactions. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
CNS Activity
Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=26164790
Curator's Comment: Penetration of blood-brain barrier was observed both in tofacitinib treated mice.
Originator
Sources: https://www.scribd.com/doc/296556203/A-Review-of-Tofacitinib-Drugs-Pros-and-Cons-of-Pharmaceuticals
Curator's Comment: Tofacitinib (formerly tasocitinib, CP-690,550 is a medicine of the janus kinase (JAK) inhibitor class, discovered and also created by the National Institutes of Health and wellness and also Pfizer. Marketed as Xeljanz and also Jakvinus. # Pfizer and O'Shea's laboratory at the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P23458 Gene ID: 3716.0 Gene Symbol: JAK1 Target Organism: Homo sapiens (Human) |
112.0 nM [IC50] | ||
Target ID: O60674 Gene ID: 3717.0 Gene Symbol: JAK2 Target Organism: Homo sapiens (Human) |
20.0 nM [IC50] | ||
Target ID: P52333 Gene ID: 3718.0 Gene Symbol: JAK3 Target Organism: Homo sapiens (Human) |
1.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Secondary | XELJANZ Approved UseIs indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. It may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs). XELJANZ should not be used in combination with biologic DMARDs or potent immunosuppressants such as azathioprine and cyclosporine. Launch Date2012 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
44.1 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26970526 |
5 mg 2 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TOFACITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
38.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26970526 |
11 mg 1 times / day steady-state, oral dose: 11 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TOFACITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
41.2 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26970526 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOFACITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
36.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26970526 |
11 mg single, oral dose: 11 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOFACITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
346.9 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01743677 |
100 mg single, oral dose: 100 mg route of administration: oral experiment type: single co-administered: |
TOFACITINIB plasma | Homo sapiens population: healthy age: sex: food status: |
|
565 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01743677 |
100 mg single, oral dose: 100 mg route of administration: oral experiment type: single co-administered: |
TOFACITINIB plasma | Homo sapiens population: healthy age: sex: food status: |
|
647.4 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01743677 |
100 mg single, oral dose: 100 mg route of administration: oral experiment type: single co-administered: |
TOFACITINIB plasma | Homo sapiens population: healthy age: sex: food status: |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
266.1 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26970526 |
5 mg 2 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TOFACITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
272.9 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26970526 |
11 mg 1 times / day steady-state, oral dose: 11 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TOFACITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
247.9 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26970526 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOFACITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
259.8 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26970526 |
11 mg single, oral dose: 11 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOFACITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
1673.1 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01743677 |
100 mg single, oral dose: 100 mg route of administration: oral experiment type: single co-administered: |
TOFACITINIB plasma | Homo sapiens population: healthy age: sex: food status: |
|
2669.7 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01743677 |
100 mg single, oral dose: 100 mg route of administration: oral experiment type: single co-administered: |
TOFACITINIB plasma | Homo sapiens population: healthy age: sex: food status: |
|
2670.2 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01743677 |
100 mg single, oral dose: 100 mg route of administration: oral experiment type: single co-administered: |
TOFACITINIB plasma | Homo sapiens population: healthy age: sex: food status: |
|
3114.3 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01743677 |
100 mg single, oral dose: 100 mg route of administration: oral experiment type: single co-administered: |
TOFACITINIB plasma | Homo sapiens population: healthy age: sex: food status: |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26970526 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOFACITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
5.9 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26970526 |
11 mg single, oral dose: 11 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOFACITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
3 h |
5 mg 2 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TOFACITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.201 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01743677 |
100 mg single, oral dose: 100 mg route of administration: oral experiment type: single co-administered: |
TOFACITINIB plasma | Homo sapiens population: healthy age: sex: food status: |
|
3.284 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01743677 |
100 mg single, oral dose: 100 mg route of administration: oral experiment type: single co-administered: |
TOFACITINIB plasma | Homo sapiens population: healthy age: sex: food status: |
|
3.32 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01743677 |
100 mg single, oral dose: 100 mg route of administration: oral experiment type: single co-administered: |
TOFACITINIB plasma | Homo sapiens population: healthy age: sex: food status: |
|
3.005 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01743677 |
100 mg single, oral dose: 100 mg route of administration: oral experiment type: single co-administered: |
TOFACITINIB plasma | Homo sapiens population: healthy age: sex: food status: |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
61% |
TOFACITINIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
100 mg single, oral Highest studied dose |
healthy, 18–45 years n = 8 Health Status: healthy Age Group: 18–45 years Sex: M+F Population Size: 8 Sources: |
Other AEs: Nausea... |
30 mg 2 times / day steady, oral Highest studied dose Dose: 30 mg, 2 times / day Route: oral Route: steady Dose: 30 mg, 2 times / day Sources: |
unhealthy, 54.2 years ( range: 30–71 years) n = 10 Health Status: unhealthy Age Group: 54.2 years ( range: 30–71 years) Sex: M+F Population Size: 10 Sources: |
Disc. AE: Herpes simplex skin chronic ulcers... Other AEs: Viral infection, Dehydration... AEs leading to discontinuation/dose reduction: Herpes simplex skin chronic ulcers (1 patient) Other AEs:Viral infection (severe, 1 patient) Sources: Dehydration (severe, 1 patient) |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Infection, Lymphoma... Other AEs: Infection (serious) Sources: Lymphoma |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
Disc. AE: Pneumonia, Herpes zoster... AEs leading to discontinuation/dose reduction: Pneumonia (2.5%) Sources: Page: p. 122Herpes zoster (2.5%) Aspartate aminotransferase increased (1.5%) ALT increased (1.5%) Creatinine increased (1.5%) Gastrointestinal disorders (1%) Respiratory disorder (0.4%) Eye disorders (0.1%) Skin disorder (1%) Hepatobiliary disorders (0.3%) Immune system disorders (0.1%) Psychiatric disorders (0.1%) |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
Disc. AE: Pneumonia, Herpes zoster... AEs leading to discontinuation/dose reduction: Pneumonia (2.7%) Sources: Page: p. 122Herpes zoster (2.7%) Aspartate aminotransferase increased (2%) ALT increased (2%) Creatinine increased (2%) Gastrointestinal disorders (1.5%) Respiratory disorder (0.6%) Eye disorders (0.2%) Skin disorder (0.3%) Vascular disorders (0.3%) Immune system disorders (0.1%) Reproductive system and breast disorders (0.1%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Nausea | 3 patients | 100 mg single, oral Highest studied dose |
healthy, 18–45 years n = 8 Health Status: healthy Age Group: 18–45 years Sex: M+F Population Size: 8 Sources: |
Herpes simplex skin chronic ulcers | 1 patient Disc. AE |
30 mg 2 times / day steady, oral Highest studied dose Dose: 30 mg, 2 times / day Route: oral Route: steady Dose: 30 mg, 2 times / day Sources: |
unhealthy, 54.2 years ( range: 30–71 years) n = 10 Health Status: unhealthy Age Group: 54.2 years ( range: 30–71 years) Sex: M+F Population Size: 10 Sources: |
Dehydration | severe, 1 patient | 30 mg 2 times / day steady, oral Highest studied dose Dose: 30 mg, 2 times / day Route: oral Route: steady Dose: 30 mg, 2 times / day Sources: |
unhealthy, 54.2 years ( range: 30–71 years) n = 10 Health Status: unhealthy Age Group: 54.2 years ( range: 30–71 years) Sex: M+F Population Size: 10 Sources: |
Viral infection | severe, 1 patient | 30 mg 2 times / day steady, oral Highest studied dose Dose: 30 mg, 2 times / day Route: oral Route: steady Dose: 30 mg, 2 times / day Sources: |
unhealthy, 54.2 years ( range: 30–71 years) n = 10 Health Status: unhealthy Age Group: 54.2 years ( range: 30–71 years) Sex: M+F Population Size: 10 Sources: |
Lymphoma | 5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
|
Infection | serious | 5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Eye disorders | 0.1% Disc. AE |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
Immune system disorders | 0.1% Disc. AE |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
Psychiatric disorders | 0.1% Disc. AE |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
Hepatobiliary disorders | 0.3% Disc. AE |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
Respiratory disorder | 0.4% Disc. AE |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
Gastrointestinal disorders | 1% Disc. AE |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
Skin disorder | 1% Disc. AE |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
ALT increased | 1.5% Disc. AE |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
Aspartate aminotransferase increased | 1.5% Disc. AE |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
Creatinine increased | 1.5% Disc. AE |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
Herpes zoster | 2.5% Disc. AE |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
Pneumonia | 2.5% Disc. AE |
5 mg 2 times / day steady, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1216 Health Status: unhealthy Age Group: adult Population Size: 1216 Sources: Page: p. 122 |
Immune system disorders | 0.1% Disc. AE |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
Reproductive system and breast disorders | 0.1% Disc. AE |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
Eye disorders | 0.2% Disc. AE |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
Skin disorder | 0.3% Disc. AE |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
Vascular disorders | 0.3% Disc. AE |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
Respiratory disorder | 0.6% Disc. AE |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
Gastrointestinal disorders | 1.5% Disc. AE |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
ALT increased | 2% Disc. AE |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
Aspartate aminotransferase increased | 2% Disc. AE |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
Creatinine increased | 2% Disc. AE |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
Herpes zoster | 2.7% Disc. AE |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
Pneumonia | 2.7% Disc. AE |
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: Page: p. 122 |
unhealthy, adult n = 1214 Health Status: unhealthy Age Group: adult Population Size: 1214 Sources: Page: p. 122 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 7, 33 |
no [IC50 >30 uM] | |||
Page: 7, 33 |
no [IC50 >30 uM] | |||
Page: 7, 33 |
no [IC50 >30 uM] | |||
Page: 7, 33 |
no [IC50 >30 uM] | |||
Page: 7, 9, 33 |
no [IC50 >30 uM] | no (co-administration study) Comment: tofacitinib had no substatial effect on the exposure of midazolam Page: 7, 9, 33 |
||
Page: 7.0 |
no | |||
Page: 7.0 |
no | |||
Page: 7.0 |
no | |||
Page: 7.0 |
no | |||
Page: 7, 33 |
no | |||
Page: 33.0 |
no | |||
Page: 33.0 |
no | |||
Page: 33.0 |
no | |||
Page: 33.0 |
no | |||
Page: 33.0 |
no | |||
Page: 7.0 |
weak [IC50 150 uM] | |||
Page: 7, 33 |
weak [IC50 311 uM] | |||
Page: 7.0 |
weak [IC50 55.3 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 32.0 |
minor | |||
Page: 32.0 |
minor | |||
Page: 32.0 |
minor | |||
Page: 32.0 |
minor | |||
Page: 32.0 |
minor | |||
Page: 32.0 |
minor | |||
Page: 32.0 |
minor | |||
Page: 32.0 |
minor | |||
Page: 32.0 |
minor | |||
Page: 32.0 |
minor | |||
Page: 7, 23, 33 |
no | |||
Page: 6, 8, 32, 89 |
yes | yes (co-administration study) Comment: fluconazole increased tofactinib AUC by 79% and Cmax by 27%; Page: 6, 8, 32, 89 |
||
Page: 6, 8, 32, 89 |
yes | yes (co-administration study) Comment: ketoconazole increased tofacitinib AUC by 103% and Cmax by 16%; fluconazole increased tofactinib AUC by 79% and Cmax by 27%; rifampin decreased tofacitinib AUC by 84% and Cmax by 74% Page: 6, 8, 32, 89 |
||
Page: 6, 9, 33 |
yes | yes (co-administration study) Comment: cyclosporine increased tofacitinib AUC by 73% and decreased Cmax by 17%; tofacitinib coadministration with cyclosproine is not recommended Page: 6, 9, 33 |
PubMed
Title | Date | PubMed |
---|---|---|
Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. | 2003 Oct 31 |
|
Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). | 2008 Dec 25 |
|
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. | 2010 Nov 24 |
|
Comprehensive analysis of kinase inhibitor selectivity. | 2011 Oct 30 |
|
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. | 2011 Oct 30 |
|
EGCG enhances the therapeutic potential of gemcitabine and CP690550 by inhibiting STAT3 signaling pathway in human pancreatic cancer. | 2012 |
Sample Use Guides
Recommended dose of XELJANZ is 5 mg twice daily. Recommended dose of XELJANZ XR is 11 mg once daily. Recommended dose in patients with moderate and severe renal impairment and moderate hepatic impairment is XELJANZ 5 mg once daily. Use of XELJANZ/XELJANZ XR in patients with severe hepatic impairment is not recommended.
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=14593182
0-4000 nM tofacitinib was used in human T blasts cell to measure IL-2-dependent proliferation. CP-690550 (tofacitinib) was added to freshly plated cells and cultured for 4 days.
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Classification Tree | Code System | Code | ||
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EMA ASSESSMENT REPORTS |
XELJANZ (REFUSED: ARTHRITIS, RHEUMATOID)
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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NCI_THESAURUS |
C1967
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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Code System | Code | Type | Description | ||
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10174505
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | |||
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DTXSID80202404
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | |||
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C95801
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | |||
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XELJANZ
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | APPROVED MARCH 2013 | ||
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m10931
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | Merck Index | ||
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SUB33105
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | |||
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O1FF4DIV0D
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | |||
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DBSALT000180
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | |||
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1358492
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | RxNorm | ||
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WW-12
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | |||
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O1FF4DIV0D
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | |||
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71197
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | |||
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100000126136
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | |||
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540737-29-9
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY | |||
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CHEMBL221959
Created by
admin on Fri Dec 15 18:46:21 GMT 2023 , Edited by admin on Fri Dec 15 18:46:21 GMT 2023
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PRIMARY |
ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD