Ruxolitinib

SKU: orb1307364

Description

Ruxolitinib is a potent and selective JAK1/2 inhibitor (IC50=3.3/2.8 nM). It demonstrates antitumor effects by inducing autophagy and apoptosis, making it a valuable tool for in vitro and in vivo research in oncology and immunology.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 941678-49-5
• MW: 306.37
• Purity: >98%
• Formula: C₁₇H₁₈N₆
• SMILES: N#CC[C@H](C1CCCC1)n1cc(cn1)-c1ncnc2[nH]ccc12
• Target: Kinase
• Solubility: Soluble in DMSO (up to 28 mg/ml) or in Ethanol (up to 15 mg/ml with warming).

Bioactivity

• Target IC50:
  JAK2:2.8 nM (cell free)|JAK1:3.3 nM (cell free)|TYK2:19 nM (cell free)|JAK3:428 nM
• In Vivo:
  METHODS: To assay antitumor activity in vivo, Ruxolitinib (3-30 mg/kg, 5% dimethyl acetamide, 0.5% methocellulose) was administered by gavage to BALB/c mice harboring the tumor Ba/F3-JAK2V617F twice daily for three weeks. RESULTS: Ruxolitinib significantly reduced splenomegaly and circulating levels of inflammatory cytokines and preferentially eliminated tumor cells, resulting in significantly prolonged survival without myelosuppressive or immunosuppressive effects. METHODS: To assay antitumor activity in vivo, Ruxolitinib (150 mg/kg) was orally administered to BALB/c nude mice bearing the human colorectal tumor LS411N every two days for two weeks. RESULTS: Oral administration of Ruxolitinib significantly inhibited the growth of human colorectal tumors in vivo without causing hepatotoxicity.
• In Vitro:
  METHODS: Ba/F3-EpoR-JAK2V617F cells were treated with Ruxolitinib (0-10 μM) for 48 h. Cell viability was measured using Cell-Titer Glo. RESULTS: Ruxolitinib dose-dependently decreased cell viability with an IC50 of 126 nM. METHODS: Hodgkin's lymphoma cells HDLM-2 were treated with Ruxolitinib (10-100 nM) for 24 h, and the expression levels of target proteins were detected by Western Blot. RESULTS: Ruxolitinib significantly inhibited the downstream activities of p-STAT3 and p-STAT5 in a dose-dependent manner, while total STAT3 and STAT5 levels remained unchanged.
• Cell Research:
  Cells were seeded at 2000/well of white bottom 96-well plates, treated with compounds from DMSO stocks (0.2% final DMSO concentration), and incubated for 48 hours at 37°C with 5% CO2. Viability was measured by cellular ATP determination using the Cell-Titer Glo luciferase reagent or viable cell counting. Values were transformed to percent inhibition relative to vehicle control, and IC50 curves were fitted according to nonlinear regression analysis of the data using PRISM GraphPad .
• Animal Research:
  All of the procedures were conducted in accordance with the US Public Health Service Policy on Humane Care and Use of Laboratory Animals. Mice were fed standard rodent chow and provided with water ad libitum. Ba/F3-JAK2V617F cells (10^5 per mouse) were inoculated intravenously into 6- to 8-week-old female BALB/c mice. Survival was monitored daily, and moribund mice were humanely killed and considered deceased at time of death. Treatment with vehicle (5% dimethylacetamide, 0.5% methocellulose) or INCB018424 began within 24 hours of cell inoculation, twice daily by oral gavage. Hematologic parameters were measured using a Bayer Advia120 analyzed, and statistical significance was determined using Dunnett testing .

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

INCB 018424

Compound Identifiers

PubChem CID

25126798