Ruxolitinib

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H18N6
Molecular Weight	306.365
Optical Activity	( - )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N#CC[C@H](C1CCCC1)N2C=C(C=N2)C3=NC=NC4=C3C=CN4

InChI

InChIKey=HFNKQEVNSGCOJV-OAHLLOKOSA-N

InChI=1S/C17H18N6/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)/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

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 39 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 8504		3.3 nM [IC50]
Tyrosine-protein kinase JAK2 59 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 8504		2.8 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Primary myelofibrosis 10 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202192s012lbl.pdf	Primary		Approved 8583	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 18 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202192s012lbl.pdf	Primary		Approved 8583	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
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 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
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 plasma	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 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	Analyte	Population
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 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
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 plasma	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 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

T_1/2

Value	Dose	Analyte	Population
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 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
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 plasma	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 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

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	unhealthy, Median age 62 years Health Status: unhealthy Age Group: Median age 62 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf	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
72 mg 1 times / day multiple, oral 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 Health Status: unhealthy Age Group: Median age 65 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/20843246/	Other AEs: Fatigue, Asthenia... Other AEs: Fatigue (grade 3, 1.3%) 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%) 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 Health Status: unhealthy Age Group: Median age 67 years Sex: M+F 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	unhealthy, Median age 67 years Health Status: unhealthy Age Group: Median age 67 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf	Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 4, 6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf
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 Health Status: unhealthy Age Group: Median age 71 years Sex: M+F 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	unhealthy, Median age 75 years Health Status: unhealthy Age Group: Median age 75 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf	Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 4, 33%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.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 https://www.ema.europa.eu/en/documents/assessment-report/jakavi-epar-public-assessment-report_en.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F 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	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000MedR.pdf	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

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087 inhibitor 2252	inhibitor 2438 substrate 1193	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 P-gp 1741 BCRP 910 OATP1B1 1079 OATP1B3 961 OCT1 620 OCT2 779 OAT1 725 OAT3 747	CYP1A2 1197 CYP2C19 1119	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=6 Page: -	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=6 Page: -	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=6 Page: -	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=8 Page: -	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	yes [IC50 19.3 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	yes [IC50 20.5 uM]
P-gp 1932	inhibitor 4027 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 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	yes [IC50 48 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	yes [IC50 6.5 uM]
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	yes [IC50 9.1 uM]
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=40 Page: -	yes [IC50 9.8 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=38 Page: -	yes [IC50 >25 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=38 Page: -	yes [IC50 >25 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=38 Page: -	yes [IC50 >25 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=38 Page: -	yes [IC50 >25 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=38 Page: -	yes [IC50 >25 uM]
CYP2D6 2546	inhibitor 4027 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 1946	substrate 4014 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 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=23 Page: -	minor
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=23 Page: -	minor
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202192Orig1s000ClinPharmR.pdf#page=23 Page: -	minor
CYP2D6 1388	substrate 4014 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 2263	inhibitor 2237 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
The novel Janus kinase inhibitor ruxolitinib confers protection against carbon tetrachloride-induced hepatotoxicity via multiple mechanisms.	2014-09-05	24973641
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.	2014-09	25129481
The evaluation of p,p'-DDT exposure on cell adhesion of hepatocellular carcinoma.	2014-08-01	24820114
JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis.	2014	24883332
Ruxolitinib and tofacitinib are potent and selective inhibitors of HIV-1 replication and virus reactivation in vitro.	2014	24419350
Myelofibrosis: an update on current pharmacotherapy and future directions.	2013-05	23514013
Discovery of potent and selective pyrazolopyrimidine janus kinase 2 inhibitors.	2012-11-26	23061660
Ruxolitinib: in the treatment of myelofibrosis.	2012-11-12	23061804
Comprehensive analysis of kinase inhibitor selectivity.	2011-10-30	22037378
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010-11-24	21095574
Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms.	2010-04-15	20130243

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 `Mon Mar 31 19:02:46 GMT 2025` Edited by `admin` on `Mon Mar 31 19:02:46 GMT 2025`
Record UNII	82S8X8XX8H
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Ruxolitinib

Official Name

English

ruxolitinib [INN]

Preferred Name

English

RUXOLITINIB [VANDF]

Common Name

English

INCB018424

Code

English

INC424

Code

English

RUXOLITINIB [USAN]

Common Name

English

Ruxolitinib [WHO-DD]

Common Name

English

INCB-018424

Code

English

RUXOLITINIB [MI]

Common Name

English

INC-424

Code

English

(3R)-3-CYCLOPENTYL-3-(4-(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YL)PYRAZOL-1-YL)PROPANENITRILE

Systematic Name

English

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

Common Name

English

INCB-18424

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C129825