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Details

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

SHOW SMILES / InChI
Structure of RUXOLITINIB

SMILES

N#CC[C@H](C1CCCC1)N2C=C(C=N2)C3=C4C=CNC4=NC=N3

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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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 TargetPharmacologyConditionPotency
3.3 nM [IC50]
2.8 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
JAKAFI
Primary
JAKAFI

Cmax

ValueDoseCo-administeredAnalytePopulation
333 nM
25 mg 1 times / day multiple, oral
RUXOLITINIB plasma
Homo sapiens
1100 nM
25 mg 2 times / day multiple, oral
RUXOLITINIB plasma
Homo sapiens
5300 nM
100 mg single, oral
RUXOLITINIB unknown
Homo sapiens
613 nM
10 mg single, oral
RUXOLITINIB unknown
Homo sapiens
562 nM
10 mg 2 times / day multiple, oral
RUXOLITINIB unknown
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
3180 nM × h
25 mg 1 times / day multiple, oral
RUXOLITINIB plasma
Homo sapiens
4350 nM × h
25 mg 2 times / day multiple, oral
RUXOLITINIB plasma
Homo sapiens
21500 nM × h
100 mg single, oral
RUXOLITINIB unknown
Homo sapiens
2160 nM × h
10 mg single, oral
RUXOLITINIB unknown
Homo sapiens
2190 nM × h
10 mg 2 times / day multiple, oral
RUXOLITINIB unknown
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
5.3 h
25 mg 1 times / day multiple, oral
RUXOLITINIB plasma
Homo sapiens
2.8 h
25 mg 2 times / day multiple, oral
RUXOLITINIB plasma
Homo sapiens
3.28 h
100 mg single, oral
RUXOLITINIB unknown
Homo sapiens
2.98 h
10 mg single, oral
RUXOLITINIB unknown
Homo sapiens
2.96 h
10 mg 2 times / day multiple, oral
RUXOLITINIB unknown
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
3.3%
RUXOLITINIB plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

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
Record UNII
82S8X8XX8H
Record Status Validated (UNII)
Record Version