Ruxolitinib, Phosphate Salt **
產品名稱：Ruxolitinib, Phosphate Salt
產品貨號：LC R-6688
產品規(guī)格：100 MG
Ruxolitinib, also known as INCB18424, is a potent and selective Janus kinase JAK1 and JAK2 inhibitor, with IC50s of 2.7 and 4.5 nM, respectively. Verstovsek, S., et al. "INCB018424, an oral, selective JAK2 inhibitor, shows significant clinical activity in a phase I/II study in patients with primary myelofibrosis (PMF) and post polycythemia vera/essential thrombocythemia myelofibrosis (post-PV/ET MF)." Blood (ASH Annual Meeting Abstracts) 110: 558 (2007), see also http://www.incyte.com/ASH Presentation 12.10.07.pdf.
This product is the phosphate salt form of ruxolitinib. We also offer the free base form; please see Ruxolitinib, Free Base, Cat. No. R-6600. The phosphate salt form of ruxolitinib is used for some or all ruxolitinib formulations for use in humans.
Ruxolitinib suppressed interleukin-6 signaling (IC50 = 281 nM) and proliferation of JAK2V617F+ Ba/F3 cells (IC50 = 127 nM). In primary cell cultures, ruxolitinib more selectively inhibited erythroid progenitor colony formation from JAK2V617F+ polycythemia vera patients (IC50 = 67 nM) when compared to healthy donors (IC50 > 400 nM). In a mouse model of JAK2V617F+ myeloproliferative neoplasm, ruxolitinib significantly reduced splenomegaly and circulating levels of inflammatory cytokines, selectively eliminated neoplastic cells, and thus markedly prolonged survival without myelosuppressive or immunosuppressive effects. Quintás-Cardama, A., et al. "Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms." Blood 115: 3109-3117 (2010).
Ruxolitinib inhibited phosphorylated signal transducer and activator of transcription 3 (STAT3) in patients with wild-type JAK2 and in patients with the JAK2 V617F mutation. Ruxolitinib reduced the spleen size of the patients with myelofibrosis with or without JAK2 V617F. It also rapidly improved symptoms, including weight loss, fatigue, night sweats, and pruritus. Clinical improvements were associated with significantly reduced levels of circulating inflammatory cytokines. Verstovsek, S., et al. "Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis." N. Engl. J. Med. 363: 1117-1127 (2010).
Ruxolitinib inhibited JAK1 and JAK2, with IC50 values of 5.9 nM and 5.7 nM, respectively. It inhibited IL-6 and IL-23 effects at concentrations less than 50 nM. Ruxolitinib was effective in the rat adjuvant arthritis model and multiple murine models of arthritis. Fridman, J.S., et al. "Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050." J. Immunol. 184: 5298-5307 (2010).
Ruxolitinib had intriguing results in patients with rheumatoid arthritis and psoriasis by inhibiting inflammatory cytokine signaling, possibly through JAK1 suppression. Mesa, R.A. "Ruxolitinib, a selective JAK1 and JAK2 inhibitor for the treatment of myeloproliferative neoplasms and psoriasis." IDrugs 13: 394-403 (2010).
Ruxolitinib phosphate is the active ingredient in the drug sold under the trade name Jakafi® by Incyte Corporation. Jakafi® is currently approved in at least one country for use in patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. NOTE: THE RUXOLITINIB, PHOSPHATE SALT RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT JAKAFI® AND IS NOT FOR HUMAN USE. Jakafi® is a registered trademark of Incyte Corporation. LC Laboratories is not affiliated with Incyte Corporation, and the ruxolitinib research compounds sold by LC Laboratories are not manufactured by Incyte Corporation.
This ruxolitinib product is the phosphate salt, whose CAS number is given above. The CAS number of the free base form of ruxolitinib is 941678-49-5.
Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 200 mg/mL; very poorly soluble in ethanol; soluble in water at 8 mg/mL with warming; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A
