Ruxolitinib (INCB18424)

N. catalogoS1378 Lotto:S137820

Stampa

Dati tecnici

Formula

C17H18N6
Peso molecolare 306.37 Numero CAS 941678-49-5
Solubilità (25°C)* In vitro DMSO 61 mg/mL (199.1 mM)
Ethanol 30 mg/mL (97.92 mM)
Water Insoluble
In vivo (Aggiungere i solventi al prodotto singolarmente e in ordine.)
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.
* <1 mg/ml significa leggermente solubile o insolubile.
* Si prega di notare che Selleck testa la solubilità di tutti i composti internamente e la solubilità effettiva può differire leggermente dai valori pubblicati. Ciò è normale ed è dovuto a leggere variazioni da lotto a lotto.
* Spedizione a temperatura ambiente (I test di stabilità mostrano che questo prodotto può essere spedito senza alcuna misura di raffreddamento.)

Preparazione delle soluzioni stock

Attività biologica

Descrizione Ruxolitinib (INCB18424) è il primo inibitore potente e selettivo di JAK1/2 ad entrare in clinica con IC50 di 3,3 nM/2,8 nM in saggi acellulari, con una selettività >130 volte maggiore per JAK1/2 rispetto a JAK3. Questo composto uccide le cellule tumorali attraverso Mitophagy tossica. Induce Autophagy e potenzia Apoptosis related.
Target
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.

Protocollo (da riferimento)

Saggio della chinasi:[1]
  • Saggio di legame

    Le proteine ricombinanti vengono espresse utilizzando cellule Sf21 e vettori di baculovirus e purificate mediante cromatografia di affinità. I saggi della chinasi JAK utilizzano un saggio di fluorescenza omogeneo risolto nel tempo con il substrato peptidico (-EQEDEPEGDYFEWLE). Ogni reazione enzimatica viene eseguita con Ruxolitinib (INCB18424) o controllo, enzima JAK, 500 nM di peptide, adenosina trifosfato (ATP; 1 mM) e 2% di dimetilsolfossido (DMSO) per 1 ora. La concentrazione inibitoria del 50% (IC50) è calcolata come la concentrazione di questo composto richiesta per l'inibizione del 50% del segnale fluorescente.
Saggio cellulare:[1]
  • Linee cellulari

    Ba/F3 and HEL cells

  • Concentrazioni

    3 μM

  • Tempo di incubazione

    48 hours

  • Metodo

    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.
Studio sugli animali:[1]
  • Modelli animali

    JAK2V617F-driven mouse model

  • Dosaggi

    180 mg/kg

  • Somministrazione

    Oral gavage

Riferimenti

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

Convalida del prodotto da parte del cliente

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.

Dati da [ 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.

Dati da [ 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.

Dati da [ 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

Selleck's Ruxolitinib (INCB18424) È stato citato da 676 Pubblicazioni

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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