Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C17H18N6.ClH |
| Molecular Weight | 342.826 |
| Optical Activity | ( - ) |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.N#CC[C@H](C1CCCC1)N2C=C(C=N2)C3=NC=NC4=C3C=CN4
InChI
InChIKey=ZYSGMFZLLDZEBY-XFULWGLBSA-N
InChI=1S/C17H18N6.ClH/c18-7-5-15(12-3-1-2-4-12)23-10-13(9-22-23)16-14-6-8-19-17(14)21-11-20-16;/h6,8-12,15H,1-5H2,(H,19,20,21);1H/t15-;/m1./s1
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C17H18N6 |
| Molecular Weight | 306.365 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: description was created based on several sources, including
http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/sbd_smd_2012_jakavi_151723-eng.php;
https://www.ncbi.nlm.nih.gov/pubmed/19385672;
http://www.businesswire.com/news/home/20160406005608/en/Incyte-Acquires-Rights-Lilly-Develop-Commercialize-Ruxolitinib
Curator's Comment: description was created based on several sources, including
http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/sbd_smd_2012_jakavi_151723-eng.php;
https://www.ncbi.nlm.nih.gov/pubmed/19385672;
http://www.businesswire.com/news/home/20160406005608/en/Incyte-Acquires-Rights-Lilly-Develop-Commercialize-Ruxolitinib
Ruxolitinib (trade names Jakafi and Jakavi, by Incyte Pharmaceuticals and Novartis) is a drug for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative disorder that affects the bone marrow. It is also being investigated for the treatment of other types of cancer (such as lymphomas and pancreatic cancer), for polycythemia vera, for plaque psoriasis, and for alopecia areata. Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) known to be associated with dysregulated JAK1 and JAK2 signaling. Ruxolitinib is a Janus-associated kinase (JAK) inhibitor with potential antineoplastic and immunomodulating activities. Ruxolitinib specifically binds to and inhibits protein tyrosine kinases JAK 1 and 2, which may lead to a reduction in inflammation and an inhibition of cellular proliferation. The JAK-STAT (signal transducer and activator of transcription) pathway plays a key role in the signaling of many cytokines and growth factors and is involved in cellular proliferation, growth, hematopoiesis, and the immune response; JAK kinases may be upregulated in inflammatory diseases, myeloproliferative disorders, and various malignancies. In a mouse model of JAK2V617F-positive MPN, ruxolitinib prevented splenomegaly, preferentially decreased JAK2V617F mutant cells in the spleen and decreased circulating inflammatory cytokines (eg, TNF-α, IL-6). Ruxolitinib was initially synthesized at Incyte Corporation that acquired the rights to develop and commercialize the drug in US. Incyte amended its Collaboration and License Agreement with Novartis, granting Novartis exclusive research, development and commercialization rights for ruxolitinib outside the U.S.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: P23458 Gene ID: 3716.0 Gene Symbol: JAK1 Target Organism: Homo sapiens (Human) |
3.3 nM [IC50] | ||
Target ID: O60674 Gene ID: 3717.0 Gene Symbol: JAK2 Target Organism: Homo sapiens (Human) |
2.8 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | JAKAFI Approved UseIndicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis and polycythemia vera who have had an inadequate response to or are
intolerant of hydroxyurea Launch Date2011 |
|||
| Primary | JAKAFI Approved UseIndicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis and polycythemia vera who have had an inadequate response to or are
intolerant of hydroxyurea Launch Date2011 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
613 nM |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
5300 nM |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
562 nM |
10 mg 2 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
1100 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30105794 |
25 mg 2 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
333 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30105794 |
25 mg 1 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2160 nM × h |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
21500 nM × h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
2190 nM × h |
10 mg 2 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
4350 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30105794 |
25 mg 2 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
3180 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30105794 |
25 mg 1 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2.98 h |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
3.28 h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
2.96 h |
10 mg 2 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
2.8 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30105794 |
25 mg 2 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
5.3 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30105794 |
25 mg 1 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RUXOLITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3.3% |
RUXOLITINIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
50 mg 2 times / day multiple, oral Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: |
unhealthy, Median age 62 years Health Status: unhealthy Age Group: Median age 62 years Sex: M+F Sources: |
DLT: Thrombocytopenia... Disc. AE: Thrombocytopenia... Other AEs: Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 20%) AEs leading todiscontinuation/dose reduction: Thrombocytopenia (grade 3, 40%) Other AEs:Thrombocytopenia (grade 3, 60%) Sources: |
72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
Other AEs: Fatigue, Asthenia... Other AEs: Fatigue (grade 3, 1.3%) Sources: Asthenia (grade 3, 2%) Fever (grade 3, 0.7%) Anxiety (grade 3, 1.3%) Insomnia (grade 3, 1.3%) Pneumonia (0.7%) Fever (1.3%) Anemia (2%) Asthenia (2%) Systemic inflammatory response syndrome (1.3%) Anxiety (1.3%) Constitutional syndrome (1.3%) Insomnia (1.3%) |
25 mg 2 times / day multiple, oral MTD Dose: 25 mg, 2 times / day Route: oral Route: multiple Dose: 25 mg, 2 times / day Sources: |
unhealthy, Median age 67 years Health Status: unhealthy Age Group: Median age 67 years Sex: M+F Sources: |
Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 3, 23%) Sources: |
25 mg 2 times / day multiple, oral MTD Dose: 25 mg, 2 times / day Route: oral Route: multiple Dose: 25 mg, 2 times / day Sources: |
unhealthy, Median age 67 years Health Status: unhealthy Age Group: Median age 67 years Sex: M+F Sources: |
Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 4, 6%) Sources: |
100 mg 1 times / day multiple, oral MTD Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: |
unhealthy, Median age 71 years Health Status: unhealthy Age Group: Median age 71 years Sex: M+F Sources: |
Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 3, 33%) Sources: |
200 mg 1 times / day multiple, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, Median age 75 years Health Status: unhealthy Age Group: Median age 75 years Sex: M+F Sources: |
Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 4, 33%) Sources: |
20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 3, 7.1%) Sources: |
20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
Disc. AE: Thrombocytopenia, Neutropenia... Other AEs: Anemia, Diarrhea... AEs leading to discontinuation/dose reduction: Thrombocytopenia (1%) Other AEs:Neutropenia (1%) Anemia (1%) Diarrhea (1%) Septic shock (1%) Subdural hematoma (1%) Hemorrhage retroperitoneal (1%) Anemia (grade 3, 10.3%) Sources: Diarrhea (grade 3, 1.9%) Epistaxis (grade 3, 0.6%) Dizziness (grade 3, 0.6%) Pneumonia (grade 3, 3.2%) Thrombocytopenia (grade 4, 1.3%) Anemia (grade 4, 5.2%) Pneumonia (grade 4, 1.9%) Thrombocytopenia (34%) Anemia (31%) Headache (15%) Dizziness (15%) Confusion (14%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Thrombocytopenia | grade 3, 40% Disc. AE |
50 mg 2 times / day multiple, oral Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: |
unhealthy, Median age 62 years Health Status: unhealthy Age Group: Median age 62 years Sex: M+F Sources: |
| Thrombocytopenia | grade 3, 60% | 50 mg 2 times / day multiple, oral Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: |
unhealthy, Median age 62 years Health Status: unhealthy Age Group: Median age 62 years Sex: M+F Sources: |
| Thrombocytopenia | grade 4, 20% DLT |
50 mg 2 times / day multiple, oral Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: |
unhealthy, Median age 62 years Health Status: unhealthy Age Group: Median age 62 years Sex: M+F Sources: |
| Pneumonia | 0.7% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Anxiety | 1.3% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Constitutional syndrome | 1.3% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Fever | 1.3% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Insomnia | 1.3% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Systemic inflammatory response syndrome | 1.3% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Anemia | 2% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Asthenia | 2% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Fever | grade 3, 0.7% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Anxiety | grade 3, 1.3% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Fatigue | grade 3, 1.3% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Insomnia | grade 3, 1.3% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Asthenia | grade 3, 2% | 72 mg 1 times / day multiple, oral Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: |
| Thrombocytopenia | grade 3, 23% | 25 mg 2 times / day multiple, oral MTD Dose: 25 mg, 2 times / day Route: oral Route: multiple Dose: 25 mg, 2 times / day Sources: |
unhealthy, Median age 67 years Health Status: unhealthy Age Group: Median age 67 years Sex: M+F Sources: |
| Thrombocytopenia | grade 4, 6% | 25 mg 2 times / day multiple, oral MTD Dose: 25 mg, 2 times / day Route: oral Route: multiple Dose: 25 mg, 2 times / day Sources: |
unhealthy, Median age 67 years Health Status: unhealthy Age Group: Median age 67 years Sex: M+F Sources: |
| Thrombocytopenia | grade 3, 33% | 100 mg 1 times / day multiple, oral MTD Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: |
unhealthy, Median age 71 years Health Status: unhealthy Age Group: Median age 71 years Sex: M+F Sources: |
| Thrombocytopenia | grade 4, 33% | 200 mg 1 times / day multiple, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, Median age 75 years Health Status: unhealthy Age Group: Median age 75 years Sex: M+F Sources: |
| Thrombocytopenia | grade 3, 7.1% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Anemia | 1% Disc. AE |
20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Diarrhea | 1% Disc. AE |
20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Hemorrhage retroperitoneal | 1% Disc. AE |
20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Neutropenia | 1% Disc. AE |
20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Septic shock | 1% Disc. AE |
20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Subdural hematoma | 1% Disc. AE |
20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Thrombocytopenia | 1% Disc. AE |
20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Confusion | 14% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Dizziness | 15% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Headache | 15% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Anemia | 31% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Thrombocytopenia | 34% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Dizziness | grade 3, 0.6% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Epistaxis | grade 3, 0.6% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Diarrhea | grade 3, 1.9% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Anemia | grade 3, 10.3% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Pneumonia | grade 3, 3.2% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Thrombocytopenia | grade 4, 1.3% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Pneumonia | grade 4, 1.9% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
| Anemia | grade 4, 5.2% | 20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| yes [IC50 19.3 uM] | ||||
| yes [IC50 20.5 uM] | ||||
| yes [IC50 21 uM] | unlikely |
|||
| yes [IC50 48 uM] | ||||
| yes [IC50 6.5 uM] | ||||
| yes [IC50 9.1 uM] | ||||
| yes [IC50 9.8 uM] | ||||
| yes [IC50 >25 uM] | ||||
| yes [IC50 >25 uM] | ||||
| yes [IC50 >25 uM] | ||||
| yes [IC50 >25 uM] | ||||
| yes [IC50 >25 uM] | ||||
| yes [IC50 >25 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| major | yes (co-administration study) Comment: 3A4 is the predominant human CYP isozyme responsible for the metabolism of ruxolitinib. Systemic co-administration of oral ketoconazole, a potent CYP3A4 inhibitor, resulted in a 91% increase of plasma AUC, whereas erythromycin, a moderate CYP3A4 inhibitor, caused a 27% increase in exposure. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=6 Page: - |
|||
| minor | ||||
| minor | ||||
| minor | ||||
| minor |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| The novel Janus kinase inhibitor ruxolitinib confers protection against carbon tetrachloride-induced hepatotoxicity via multiple mechanisms. | 2014-09-05 |
|
| Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. | 2014-09 |
|
| The evaluation of p,p'-DDT exposure on cell adhesion of hepatocellular carcinoma. | 2014-08-01 |
|
| JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis. | 2014 |
|
| Ruxolitinib and tofacitinib are potent and selective inhibitors of HIV-1 replication and virus reactivation in vitro. | 2014 |
|
| Myelofibrosis: an update on current pharmacotherapy and future directions. | 2013-05 |
|
| Discovery of potent and selective pyrazolopyrimidine janus kinase 2 inhibitors. | 2012-11-26 |
|
| Ruxolitinib: in the treatment of myelofibrosis. | 2012-11-12 |
|
| Comprehensive analysis of kinase inhibitor selectivity. | 2011-10-30 |
|
| Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. | 2010-11-24 |
|
| Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. | 2010-04-15 |
Sample Use Guides
20 mg given orally twice daily for patients with a platelet count greater than 200 X 10^9/L, and 15 mg twice daily for patients with a platelet count between 100 X 10^9/L and 200 X 10^9/L
Route of Administration:
Oral
Ba/F3 cells and HEL cells were used to evaluate the effects of INCB018424 on viability and JAK-mediated signaling. Cells were treated with increasing concentrations of INCB018424 in the concentration range of 3-3000 nM for 2.5 hours, and extracts from these cells were subjected to immunoblot analysis for phosphorylated or total forms of proteins associated with the JAK/STAT signaling pathway..
| Substance Class |
Chemical
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