Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C17H18N6.H3O4P |
| Molecular Weight | 404.3602 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OP(O)(O)=O.N#CC[C@H](C1CCCC1)N2C=C(C=N2)C3=C4C=CNC4=NC=N3
InChI
InChIKey=JFMWPOCYMYGEDM-XFULWGLBSA-N
InChI=1S/C17H18N6.H3O4P/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;1-5(2,3)4/h6,8-12,15H,1-5H2,(H,19,20,21);(H3,1,2,3,4)/t15-;/m1./s1
| 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 |
| Molecular Formula | H3O4P |
| Molecular Weight | 97.9952 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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 Date1.32140158E12 |
|||
| 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 Date1.32140158E12 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
|
5300 nM |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUXOLITINIB unknown | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
613 nM |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUXOLITINIB unknown | 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 unknown | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
|
21500 nM × h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUXOLITINIB unknown | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
2160 nM × h |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUXOLITINIB unknown | 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 unknown | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
|
3.28 h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUXOLITINIB unknown | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
2.98 h |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUXOLITINIB unknown | 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 unknown | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
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: Page: 202192Orig1s000MedR.pdf - p.24 |
unhealthy, Median age 62 years n = 5 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 62 years Sex: M+F Population Size: 5 Sources: Page: 202192Orig1s000MedR.pdf - p.24 |
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: Page: 202192Orig1s000MedR.pdf - p.24 |
72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
Other AEs: Asthenia, Fever... Other AEs: Asthenia (grade 3, 2%) Sources: Fever (grade 3, 0.7%) Fatigue (grade 3, 1.3%) 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 n = 47 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 67 years Sex: M+F Population Size: 47 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: Page: 202192Orig1s000MedR.pdf - p.24 |
unhealthy, Median age 67 years n = 47 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 67 years Sex: M+F Population Size: 47 Sources: Page: 202192Orig1s000MedR.pdf - p.24 |
Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 4, 6%) Sources: Page: 202192Orig1s000MedR.pdf - p.24 |
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 n = 6 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 71 years Sex: M+F Population Size: 6 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: Page: 202192Orig1s000MedR.pdf - p.24 |
unhealthy, Median age 75 years n = 3 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 75 years Sex: M+F Population Size: 3 Sources: Page: 202192Orig1s000MedR.pdf - p.24 |
Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 4, 33%) Sources: Page: 202192Orig1s000MedR.pdf - p.24 |
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 n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
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: Page: 202192Orig1s000MedR.pdf - p.67-70Diarrhea (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: Page: 202192Orig1s000MedR.pdf - p.24 |
unhealthy, Median age 62 years n = 5 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 62 years Sex: M+F Population Size: 5 Sources: Page: 202192Orig1s000MedR.pdf - p.24 |
| 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: Page: 202192Orig1s000MedR.pdf - p.24 |
unhealthy, Median age 62 years n = 5 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 62 years Sex: M+F Population Size: 5 Sources: Page: 202192Orig1s000MedR.pdf - p.24 |
| 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: Page: 202192Orig1s000MedR.pdf - p.24 |
unhealthy, Median age 62 years n = 5 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 62 years Sex: M+F Population Size: 5 Sources: Page: 202192Orig1s000MedR.pdf - p.24 |
| Pneumonia | 0.7% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
| Anxiety | 1.3% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
| Constitutional syndrome | 1.3% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
| Fever | 1.3% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
| Insomnia | 1.3% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
| Systemic inflammatory response syndrome | 1.3% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
| Anemia | 2% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
| Asthenia | 2% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
| Fever | grade 3, 0.7% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
| Anxiety | grade 3, 1.3% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
| Fatigue | grade 3, 1.3% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
| Insomnia | grade 3, 1.3% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 Sources: |
| Asthenia | grade 3, 2% | 72 mg 1 times / day multiple, oral (mean) Dose: 72 mg, 1 times / day Route: oral Route: multiple Dose: 72 mg, 1 times / day Sources: |
unhealthy, Median age 65 years n = 153 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 65 years Sex: M+F Population Size: 153 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 n = 47 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 67 years Sex: M+F Population Size: 47 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: Page: 202192Orig1s000MedR.pdf - p.24 |
unhealthy, Median age 67 years n = 47 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 67 years Sex: M+F Population Size: 47 Sources: Page: 202192Orig1s000MedR.pdf - p.24 |
| 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 n = 6 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 71 years Sex: M+F Population Size: 6 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: Page: 202192Orig1s000MedR.pdf - p.24 |
unhealthy, Median age 75 years n = 3 Health Status: unhealthy Condition: myelofibrosis Age Group: Median age 75 years Sex: M+F Population Size: 3 Sources: Page: 202192Orig1s000MedR.pdf - p.24 |
| 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 n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
| 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: Page: 202192Orig1s000MedR.pdf - p.67-70 |
unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: Page: 202192Orig1s000MedR.pdf - p.67-70 |
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 |
|---|---|---|
| Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. | 2010 Apr 15 |
|
| 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 |
|
| Ruxolitinib: in the treatment of myelofibrosis. | 2012 Nov 12 |
|
| Discovery of potent and selective pyrazolopyrimidine janus kinase 2 inhibitors. | 2012 Nov 26 |
|
| Myelofibrosis: an update on current pharmacotherapy and future directions. | 2013 May |
|
| 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 |
|
| The evaluation of p,p'-DDT exposure on cell adhesion of hepatocellular carcinoma. | 2014 Aug 1 |
|
| Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. | 2014 Sep |
|
| The novel Janus kinase inhibitor ruxolitinib confers protection against carbon tetrachloride-induced hepatotoxicity via multiple mechanisms. | 2014 Sep 5 |
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
Created
by
admin
on
Edited
Fri Dec 15 18:11:51 UTC 2023
by
admin
on
Fri Dec 15 18:11:51 UTC 2023
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| Record UNII |
436LRU32H5
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| Record Status |
Validated (UNII)
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| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
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FDA ORPHAN DRUG |
265308
Created by
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NCI_THESAURUS |
C1967
Created by
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FDA ORPHAN DRUG |
302510
Created by
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NCI_THESAURUS |
C129825
Created by
admin on Fri Dec 15 18:11:51 UTC 2023 , Edited by admin on Fri Dec 15 18:11:51 UTC 2023
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EMA ASSESSMENT REPORTS |
JAKAVI (AUTHORIZED: MYELOPROLIFERATIVE DISORDERS)
Created by
admin on Fri Dec 15 18:11:51 UTC 2023 , Edited by admin on Fri Dec 15 18:11:51 UTC 2023
|
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
25127112
Created by
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PRIMARY | |||
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C97937
Created by
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PRIMARY | |||
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1193325
Created by
admin on Fri Dec 15 18:11:51 UTC 2023 , Edited by admin on Fri Dec 15 18:11:51 UTC 2023
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PRIMARY | RxNorm | ||
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436LRU32H5
Created by
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PRIMARY | |||
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EU/3/08/572(WITHDRAWN)
Created by
admin on Fri Dec 15 18:11:51 UTC 2023 , Edited by admin on Fri Dec 15 18:11:51 UTC 2023
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PRIMARY | Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in February 2015 on request of the sponsor. On 7 November 2008, orphan designation (EU/3/08/572) was granted by the European Commission to Incyte Corporation Ltd, United Kingdom, for (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate for the treatment of chronic idiopathic myelofibrosis. The sponsorship was transferred to Novartis Europharm Limited, United Kingdom, in September 2010. (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate in treatment of chronic idiopathic myelofibrosis has been authorised in the EU as Jakavi since 23 August 2012. | ||
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SUB32897
Created by
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PRIMARY | |||
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DBSALT000156
Created by
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PRIMARY | |||
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DTXSID00911086
Created by
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PRIMARY | |||
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100000126279
Created by
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PRIMARY | |||
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436LRU32H5
Created by
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PRIMARY | |||
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UU-161
Created by
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PRIMARY | |||
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m9710
Created by
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PRIMARY | Merck Index | ||
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CHEMBL1789941
Created by
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PRIMARY | |||
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66917
Created by
admin on Fri Dec 15 18:11:51 UTC 2023 , Edited by admin on Fri Dec 15 18:11:51 UTC 2023
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PRIMARY | |||
|
EU/3/09/620(WITHDRAWN)
Created by
admin on Fri Dec 15 18:11:51 UTC 2023 , Edited by admin on Fri Dec 15 18:11:51 UTC 2023
|
PRIMARY | Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in February 2015 on request of the sponsor. On 3 April 2009, orphan designation (EU/3/09/620) was granted by the European Commission to Incyte Corporation Ltd, United Kingdom, for (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate for the treatment of myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia. The sponsorship was transferred to Novartis Europharm Limited, United Kingdom, in September 2010. R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate in treatment of myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia has been authorised in the EU as Jakavi since 23 August 2012. | ||
|
1092939-17-7
Created by
admin on Fri Dec 15 18:11:51 UTC 2023 , Edited by admin on Fri Dec 15 18:11:51 UTC 2023
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PRIMARY |
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PARENT -> SALT/SOLVATE |
| Related Record | Type | Details | ||
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ACTIVE MOIETY |