RUXOLITINIB PHOSPHATE

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

Structure Search

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

HIDE SMILES / InChI

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202192s012lbl.pdf
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase JAK1 38 Target ID: P23458 Gene ID: 3716.0 Gene Symbol: JAK1 Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202192s012lbl.pdf	Inhibitor 8297		3.3 nM [IC50]
Tyrosine-protein kinase JAK2 55 Target ID: O60674 Gene ID: 3717.0 Gene Symbol: JAK2 Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202192s012lbl.pdf	Inhibitor 8297		2.8 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Primary myelofibrosis 7 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202192s012lbl.pdf	Primary		Approved 8429	JAKAFI Approved Use Indicated 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 Date 2011
Polycythemia vera 15 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202192s012lbl.pdf	Primary		Approved 8429	JAKAFI Approved Use Indicated 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 Date 2011

C_max

Value	Dose	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 EXPERIMENT https://doi.org/10.1182/blood.V118.21.5162.5162	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 EXPERIMENT https://doi.org/10.1182/blood.V118.21.5162.5162	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 EXPERIMENT https://doi.org/10.1182/blood.V118.21.5162.5162	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	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 EXPERIMENT https://doi.org/10.1182/blood.V118.21.5162.5162	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 EXPERIMENT https://doi.org/10.1182/blood.V118.21.5162.5162	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 EXPERIMENT https://doi.org/10.1182/blood.V118.21.5162.5162	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

T_1/2

Value	Dose	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 EXPERIMENT https://doi.org/10.1182/blood.V118.21.5162.5162	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 EXPERIMENT https://doi.org/10.1182/blood.V118.21.5162.5162	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 EXPERIMENT https://doi.org/10.1182/blood.V118.21.5162.5162	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
3.3% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf			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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf Page: 202192Orig1s000MedR.pdf - p.24	DLT: Thrombocytopenia... Disc. AE: Thrombocytopenia... Other AEs: Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 20%) AEs leading to discontinuation/dose reduction: Thrombocytopenia (grade 3, 40%) Other AEs: Thrombocytopenia (grade 3, 60%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf 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: https://pubmed.ncbi.nlm.nih.gov/20843246/	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: https://pubmed.ncbi.nlm.nih.gov/20843246/	Other AEs: Asthenia, Fever... Other AEs: Asthenia (grade 3, 2%) 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%) Sources: https://pubmed.ncbi.nlm.nih.gov/20843246/
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/20843246/	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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/20843246/	Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 3, 23%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/20843246/
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf Page: 202192Orig1s000MedR.pdf - p.24	Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 4, 6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/20843246/	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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/20843246/	Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 3, 33%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/20843246/
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf Page: 202192Orig1s000MedR.pdf - p.24	Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 4, 33%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf https://www.ema.europa.eu/en/documents/assessment-report/jakavi-epar-public-assessment-report_en.pdf	unhealthy, adult n = 155 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: M+F Population Size: 155 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf https://www.ema.europa.eu/en/documents/assessment-report/jakavi-epar-public-assessment-report_en.pdf	Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 3, 7.1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf https://www.ema.europa.eu/en/documents/assessment-report/jakavi-epar-public-assessment-report_en.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf Page: 202192Orig1s000MedR.pdf - p.67-70	Disc. AE: Thrombocytopenia, Neutropenia... Other AEs: Anemia, Diarrhea... AEs leading to discontinuation/dose reduction: Thrombocytopenia (1%) Neutropenia (1%) Anemia (1%) Diarrhea (1%) Septic shock (1%) Subdural hematoma (1%) Hemorrhage retroperitoneal (1%) Other AEs: Anemia (grade 3, 10.3%) 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%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf Page: 202192Orig1s000MedR.pdf - p.67-70

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inducer 781 inhibitor 1587	inhibitor 1767 substrate 1037	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 P-gp 1461 BCRP 699 OATP1B1 788 OATP1B3 706 OCT1 512 OCT2 647 OAT1 599 OAT3 642	CYP1A2 1054 CYP2C19 991	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=6 Page: -	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=6 Page: -	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=6 Page: -	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=8 Page: -	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	yes [IC50 19.3 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	yes [IC50 20.5 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=8 Page: -	yes [IC50 21 uM]	unlikely Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=8 Page: -
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	yes [IC50 48 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	yes [IC50 6.5 uM]
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	yes [IC50 9.1 uM]
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	yes [IC50 9.8 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=38 Page: -	yes [IC50 >25 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=38 Page: -	yes [IC50 >25 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=38 Page: -	yes [IC50 >25 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=38 Page: -	yes [IC50 >25 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=38 Page: -	yes [IC50 >25 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=38 Page: -	yes [IC50 >25 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=6 Page: -	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: -
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=23 Page: -	minor
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=23 Page: -	minor
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=23 Page: -	minor
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=23 Page: -	minor

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000PharmR.pdf#page=29 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:66919	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:66919
ChemicalBook	CB02499581	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB02499581
MolPort	MolPort-020-006-045	https://www.molport.com/shop/molecule-link/MolPort-020-006-045
MolPort	MolPort-046-196-087	https://www.molport.com/shop/molecule-link/MolPort-046-196-087
Selleck Chemicals	INCB18424	http://www.selleckchem.com/products/INCB18424.html
ZINC	ZINC000043207851	http://zinc15.docking.org/substances/ZINC000043207851

PubMed

Title	Date	PubMed
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010 Nov 24	21095574
Comprehensive analysis of kinase inhibitor selectivity.	2011 Oct 30	22037378
JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis.	2014	24883332
The evaluation of p,p'-DDT exposure on cell adhesion of hepatocellular carcinoma.	2014 Aug 1	24820114
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.	2014 Sep	25129481
The novel Janus kinase inhibitor ruxolitinib confers protection against carbon tetrachloride-induced hepatotoxicity via multiple mechanisms.	2014 Sep 5	24973641

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Fri Dec 15 18:11:51 GMT 2023` Edited by `admin` on `Fri Dec 15 18:11:51 GMT 2023`
Record UNII	436LRU32H5
Record Status	`Validated (UNII)`
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Name

Type

Language

RUXOLITINIB PHOSPHATE

Official Name

English

1H-PYRAZOLE-1-PROPANENITRILE,.BETA.-CYCLOPENTYL-4-(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YL)-,(.BETA.R)-,PHOSPHATE (1:1)

Common Name

English

INCB-018424 PHOSPHATE

Code

English

RUXOLITINIB (AS PHOSPHATE) [EMA EPAR]

Common Name

English

RUXOLITINIB PHOSPHATE [MI]

Common Name

English

JAKAVI

Brand Name

English

RUXOLITINIB PHOSPHATE [ORANGE BOOK]

Common Name

English

RUXOLITINIB MONOPHOSPHATE

Common Name

English

Ruxolitinib phosphate [WHO-DD]

Common Name

English

INCB018424 PHOSPHATE

Code

English

(3R)-3-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile phosphate (1:1)

Systematic Name

English

JAKAFI

Brand Name

English

RUXOLITINIB (AS PHOSPHATE)

Common Name

English

INCB-18424 PHOSPHATE

Code

English

OPZELURA

Brand Name

English

RUXOLITINIB PHOSPHATE [USAN]

Common Name

English

INCB-018424 SALT

Code

English

RUXOLITINIB PHOSPHATE [JAN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

265308