Ruxolitinib (INCB18424)

Katalognr.S1378 Batch:S137821

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Tekniska data

Formel

C17H18N6
Molekylvikt 306.37 CAS-nr. 941678-49-5
Löslighet (25°C)* In vitro DMSO 300 mg/mL (979.2 mM)
Ethanol 12 mg/mL (39.16 mM)
Water Insoluble
In Vivo (Tillsätt lösningsmedel till produkten individuellt och i ordning.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG 300 5%Tween80 50% ddH2O

Validerad av Selleck-laboratorier. Om du behöver justeringar av denna formulering, kontakta vårt säljteam för skräddarsydd testning.

 3.000mg/ml (9.79mM) Taking the 1 mL working solution as an example, add 50 μL of 60 mg/mL clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween-80 to the above system, mix evenly to clarify it; then continue Add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 95% Corn oil

Validerad av Selleck-laboratorier. Om du behöver justeringar av denna formulering, kontakta vårt säljteam för skräddarsydd testning.

 3.000mg/ml (9.79mM) Taking the 1 mL working solution as an example, add 50 μL of 60 mg/mL clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml betyder svårlösligt eller olösligt.
* Vänligen notera att Selleck testar lösligheten för alla förbindelser internt, och den faktiska lösligheten kan skilja sig något från publicerade värden. Detta är normalt och beror på små variationer mellan olika partier.
* Rumstempererad frakt (Stabilitetstester visar att denna produkt kan fraktas utan några kylåtgärder.)

Beredning av stamlösningar

Biologisk aktivitet

Beskrivning Ruxolitinib (INCB18424) är den första potenta, selektiva JAK1/2-hämmaren som används kliniskt med ett IC50-värde på 3,3 nM/2,8 nM i cellfria analyser, >130 gånger selektivitet för JAK1/2 jämfört med JAK3. Denna förening dödar tumörceller genom toxisk Mitophagy. Den inducerar Autophagy och förstärker Apoptosis related.
Mål
JAK2
(Cell-free assay)		 JAK1
(Cell-free assay)
2.8 nM 3.3 nM
In vitro Ruxolitinib (INCB18424) potently and selectively inhibits JAK2V617F-mediated signaling and proliferation in Ba/F3 cells and HEL cells. This compound markedly increases apoptosis in a dose dependent manner in Ba/F3 cells. It (64 nM) results in a doubling of cells with depolarized mitochondria in Ba/F3 cells. This chemical inhibits proliferating of erythroid progenitors from normal donors and polycythemia vera patients with IC50 of 407 nM and 223 nM, respectively. It demonstrates remarkable potency against erythroid colony formation with IC50 of 67nM.
In Vivo INCB018424 (180 mg/kg, orally, twice a day) results in a survival rate of greater than 90% by day 22 in a JAK2V617F-driven mouse model. This compound (180 mg/kg, orally, twice a day) markedly reduces splenomegaly and circulating levels of inflammatory cytokines, and preferentially eliminates neoplastic cells, resulting in significantly prolonged survival without myelosuppressive or immunosuppressive effects in a JAK2V617F-driven mouse model. In the double-blind trial of myelofibrosis, the primary end point is reached in 41.9% of patients in the Ruxolitinib (INCB18424) group as compared with 0.7% in the placebo group. It results in maintaining reduction in spleen volume and improvement of 50% or more in the total symptom score. A total of 28% of the patients in the group receiving this compound (15 mg twice daily) has at least a 35% reduction in spleen volume at week 48 in patients with myelofibrosis, as compared with 0% in the group receiving the best available therapy. The mean palpable spleen length has decreased by 56% with it but has increased by 4% with the best available therapy at week 48. Patients in the ruxolitinib group has an improvement in overall quality-of-life measures and a reduction in symptoms associated with myelofibrosis.

Protokoll (från referens)

Kinasanalys:[1]
  • Bindningsanalys

    Rekombinanta proteiner uttrycks med Sf21-celler och bakulovirusvektorer och renas med affinitetskromatografi. JAK kinasanalyser använder en homogen tidsupplöst fluorescensanalys med peptidsubstratet (-EQEDEPEGDYFEWLE). Varje enzymreaktion utförs med Ruxolitinib (INCB18424) eller kontroll, JAK enzym, 500 nM peptid, adenosintrifosfat (ATP; 1mM), och 2% dimetylsulfoxid (DMSO) under 1 timme. Den 50% hämmande koncentrationen (IC50) beräknas som koncentrationen av denna förening som krävs för hämning av 50% av den fluorescerande signalen.
Cellanalys:[1]
  • Cellinjer

    Ba/F3 and HEL cells

  • Koncentrationer

    3 μM

  • Inkubationstid

    48 hours

  • Metod

    Cells are seeded at 2 × 103/well of white bottom 96-well plates and treated with Ruxolitinib (INCB018424) from DMSO stocks (0.2% final DMSO concentration), followed by incubation for 48 hours at 37 ℃ with 5% CO2. Viability is measured by cellular ATP determination using the Cell-Titer Glo luciferase reagent or viable cell counting. Values are transformed to percent inhibition relative to vehicle control, and IC50 curves are fitted according to nonlinear regression analysis of the data using PRISM GraphPad.
Djurstudie:[1]
  • Djurmodeller

    JAK2V617F-driven mouse model

  • Doseringar

    180 mg/kg

  • Administrering

    Oral gavage

Referenser

  • https://pubmed.ncbi.nlm.nih.gov/20130243/
  • https://pubmed.ncbi.nlm.nih.gov/22375971/
  • https://pubmed.ncbi.nlm.nih.gov/22375970/

Kundvalidering av produkt

STAT3 phosphorylation as determined by phospho flow, mixed lymphocyte reactions containing BALB/c spleen-derived CD4+ T cells co-cultured with or without C57BL/6 BM-derived DC preactivated with 20 ng/mL LPS.

Data från [ Blood , 2014 , 123(24), 3832-42 ]

Miniscule 10 PFU amount of VA7-EGFP results in productive infection only in CT26LacZ cells whereas the self-limiting infection can be rescued with JAK/STAT inhibitor Ruxolitinib in CT26WT cells counteracting also the effects of exogenous IFNβ (100 U/ml) pre-treatment. Scale bar: 200 um.

Data från [ Gene Ther , 2014 , 10.1038/gt.2014.83 ]

BMDMs were isolated from wild-type mice and incubated in the different concentrations of Ruxolitinib for 1 h before stimulation with 500 U/ml IFN-β for 30 min. Levels of GAPDH as well as total and phospho-Tyr705 STAT3 were determined by immunoblotting.

Data från [ J Immunol , 2012 , 189(6), 2784-92 ]

<p> </p><p>HS578T cells were treated with indicated amount of inhibitor for 18 hr. The cells were lysed by cell lysis buffer (20 mM Tris-Cl (pH 8.0); 0.5 M NaCl; 0.25% Triton X-100; 1 mM EDTA; 1 mM EGTA; 10 mM β-glycerophosphate; 10 mM NaF; 300 µM Na3VO4; 1 mM benzamidine) containing 1 mM DTT and 2 µM PMSF. Western blot analyses were performed using cleared cell lysates resolved on sodium dodecyl sulfate (SDS)-polyacrylamide gels, transferred onto polyvinylidene difluoride (PVDF) membranes (Millipore, Billerica, MA), and probed with specific antibodies using standard procedures. Chemiluminescence reagent was purchased from  Thermo Scientific (Rockford, IL). Horseradish peroxidase-conjugated secondary antibodies from Sigma (St. Louis, MO).</p>

, , Yong Weon Yi Georgetown University

Sellecks Ruxolitinib (INCB18424) Har citerats av 676 Publikationer

Systematic design of combination therapy by targeting master regulators of coexisting diffuse midline glioma cell states [ Nat Genet, 2026, 58(5):1112-1125.] PubMed: 42020604
Biomarkers of response to neoadjuvant palbociclib plus anastrozole in endocrine-resistant estrogen receptor-positive/HER2-negative breast cancer: a phase 2 trial [ Nat Commun, 2026, 17(1):949] PubMed: 41593097
Prolonged KRAS-MAPK Inhibition Induces Interferon Signaling that Promotes Cell State Transition and Confers Therapeutic Vulnerabilities [ Cancer Res, 2026, 10.1158/0008-5472.CAN-25-4114.] PubMed: 42008116
JAK1/2 inhibitor ruxolitinib reduces aggregates in cardiac proteinopathy [ EMBO Mol Med, 2026, 10.1038/s44321-026-00411-x] PubMed: 41917326
Wntless degradation mediated by CaMKII inhibition drives endoplasmic reticulum stress and apoptosis [ Cell Rep, 2026, 45(4):117256] PubMed: 41966825
ADA2-deficient cells exhibit increased levels of cell death and metabolic disturbances [ Cell Death Discov, 2026, 12(1)167] PubMed: 41866403
Non-gene-edited neural stem cells reverse neuroinflammation and microbiota dysbiosis in a sprague-dawley rat model of autism spectrum disorder [ Transl Psychiatry, 2026, 10.1038/s41398-026-03841-w] PubMed: 41922322
The tumor suppressor NDRG2 recruits protein phosphatase 2A to suppress STAT5 phosphorylation in adult T-cell leukemia/lymphoma [ J Biol Chem, 2026, S0021-9258(26)01952-6] PubMed: 42055322
Microbial metabolite drives ageing-related clonal haematopoiesis via ALPK1 [ Nature, 2025, 10.1038/s41586-025-08938-8] PubMed: 40269158
Macrophage-derived amphiregulin induces myofibroblast transition in adipogenic lineage precursors near Staphylococcus aureus abscess in bone marrow [ Nat Commun, 2025, 16(1):8409] PubMed: 40998791

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