Ruxolitinib sulfate (INCB018424 sulfate) is the first potent, selective JAK1/2 inhibitor to enter the clinic with IC₅₀s of 3.3 nM/2.8 nM, and has > 130-fold selectivity for JAK1/2 versus JAK3.

Ruxolitinib sulfate (INCB018424 sulfate) potently and selectively inhibits JAK2V617F-mediated signaling and proliferation, markedly increases apoptosis in a dose dependent manner, and at 64 nM results in a doubling of cells with depolarized mitochondria in Ba/F3 cells. Ruxolitinib demonstrates remarkable potency against erythroid colony formation with IC₅₀ of 67 nM, and inhibits proliferating of erythroid progenitors from normal donors and polycythemia vera patients with IC₅₀ values of 407 nM and 223 nM, respectively^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Ruxolitinib (INCB018424 sulfate; 180 mg/kg, orally, twice a day) results in survive rate of greater than 90% by day 22 and markedly reduces splenomegaly and circulating levels of inflammatory cytokines, and preferentially eliminated neoplastic cells, resulting in significantly prolonged survival without myelosuppressive or immunosuppressive effects in a JAK2V617F-driven mouse model^[1].
In the Ruxolitinib group, the primary end point is reached in 41.9% of patients, as compared with 0.7% in the placebo group in the double-blind trial of myelofibrosis. Ruxolitinib results in maintaining of reduction in spleen volume and improvement of 50% or more in the total symptom score^[2].
Ruxolitinib (15 mg twice daily) treatment leads a total of 28% of the patients to have 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 Ruxolitinib 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^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

404.44

C₁₇H₂₀N₆O₄S

1092939-16-6

鲁索利替尼硫酸盐

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Quintas-Cardama A, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood, 2010, 115(15), 3109-3117.

  [2]. Verstovsek S, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med, 2012, 366(9), 799-807.

  [3]. Harrison C, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):787-98.

Recombinant proteins are expressed using Sf21 cells and baculovirus vectors and purified with affinity chromatography. JAK kinase assays use a homogeneous time-resolved fluorescence assay with the peptide substrate (-EQEDEPEGDYFEWLE). Each enzyme reaction is carried out with Ruxolitinib or control, JAK enzyme, 500 nM peptide, adenosine triphosphate (ATP; 1mM), and 2% dimethyl sulfoxide (DMSO) for 1 hour. The 50% inhibitory concentration (IC₅₀) is calculated as Ruxolitinib concentration required for inhibition of 50% of the fluorescent signal^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cells are seeded at 2 × 10³/well of white bottom 96-well plates, treated with Ruxolitinib from DMSO stocks (0.2% final DMSO concentration), and incubated for 48 hours at 37°C 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^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice^[1]
Mice are fed standard rodent chow and provided with water ad libitum. Ba/F3-JAK2V617F cells (10⁵ per mouse) are inoculated intravenously into 6- to 8-week-old female BALB/c mice. Survival is monitored daily, and moribund mice are humanely killed and considered deceased at time of death. Treatment with vehicle (5% dimethyl acetamide, 0.5% methocellulose) or Ruxolitinib begin within 24 hours of cell inoculation, twice daily by oral gavage. Hematologic parameters are measured using a Bayer Advia120 analyzed, and statistical significance is determined using Dunnett testing^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Quintas-Cardama A, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood, 2010, 115(15), 3109-3117.

  [2]. Verstovsek S, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med, 2012, 366(9), 799-807.

  [3]. Harrison C, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):787-98.