Pacritinib

製品コードS8057 バッチS805702

印刷

化学情報

Chemical Structure Synonyms SB1518 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C28H32N4O3
分子量 472.58 CAS No. 937272-79-2
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 11 mg/mL (23.27 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
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 means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Pacritinib is a potent and selective inhibitor of Janus Kinase 2 (JAK2) and Fms-Like Tyrosine Kinase-3 (FLT3) with IC50s of 23 and 22 nM in cell-free assays, respectively. Phase 3.
in vitro Pacritinib is a potent inhibitor of both wild-type JAK2 and JAK2V617F mutant (IC50= 19 nM) that is present in high frequencies among patients with MPD. Relative to JAK2, this compound is two-fold less potent against TYK2 (IC50= 50 nM), 23-fold less potent against JAK3 (IC50= 520 nM) and 56-fold less potent against JAK1 (IC50= 1280 nM). It effectively permeates cells to modulate signaling pathways downstream of JAK2, whether agonist activated or mutationally activated. This chemical induces apoptosis, cell cycle arrest and antiproliferative effects in JAK2WT- and JAK2V617F-dependent cells. It inhibits cell proliferation of Karpas 1106P and Ba/F3-JAK2V617F with IC50 of 348 and 160 nM, respectively. It inhibits endogenous colony growth derived from erythroid and myeloid progenitors with IC50 of 63 and 53 nM , respectively. [1] SB1518 also inhibits FLT3 and its mutant FLT3-D835Y(IC50= 6 nM ). This compound inhibits FLT3 phosphorylation and downstream STAT, MAPK and PI3K signaling in FLT3-internal-tandem duplication (ITD), FLT3-wt cells and primary AML blast cells. Its treatment leads to a dose-dependent decrease of pFLT3, pSTAT5, pERK1/2 and pAkt in FLT3-ITD harboring MV4-11 cells with IC50 of 80, 40, 33 and 29 nM , respectively. Treatment of the primary AML blast cells with this chemical for 3 h leads to a dose-dependent decrease of pFLT3, pSTAT3 and pSTAT5 with an IC50 below 0.5 μM. It induces apoptosis, cell cycle arrest and anti-proliferative effects in FLT3-mutant and FLT3-wt cells. It inhibits cell proliferation of FLT3-ITD-harboring cells MV4-11 and primary AML blast cells with IC50s of 47 nM and 0.19-1.3 μM, respectively. [2]
in vivo Pacritinib administrated at 150 mg/kg p.o. q.d. to JAK2V617F-dependent xenograft model, significantly ameliorates splenomegaly and hepatomegaly symptoms, with 60% normalization of spleen weight and 92% normalization of liver weight and is well tolerated without significant weight loss or any hematological toxicities, including thrombocytopenia and anemia. This compound induces dose-dependent inhibition of tumor growth of JAK2V617F-dependent SET-2 xenograft model (40% for 75 mg/kg and 61% for 150 mg/kg). [1] This chemical is efficacious in FLT3-ITD-bearing MV4-11 xenograft models. It treated once daily for 21 consecutive days, induces dose-dependent inhibition of tumor growth (38% for 25 mg/kg, 92% for 50 mg/kg and 121% for 100 mg/kg). Complete regression is observed in 3/10 and 8/8 mice for the 50 and 100 mg/kg/day groups, respectively. [2]
特徴 Dual JAK2/FLT3 inhibitor that has progressed to Phase III clinical trials for treatment of Myelofibrosis.

プロトコル(参考用のみ)

キナーゼアッセイ kinase activity assays
All assays are carried out in 384-well white microtiter plates. Compounds are 4-fold serially diluted in 8 steps, starting from 10 μM. The reaction mixture consisted of 25 μL assay buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 5 mM MnCl2, 1 mM DTT, 0.1 mM Na3VO4, 5 mM β-glycerol phosphate). For FLT3 assays, the reaction contains 2.0 μg/mL FLT3 enzyme, 5 μM of poly(Glu,Tyr) substrate and 4 μM of ATP. For JAK1 assays, the reaction contains 2.5 μg/mL of JAK1 enzyme, 10 μM of poly(Glu,Ala,Tyr) substrate and 1.0 μM of ATP. For JAK2 assays, the reaction contained 0.35 μg/mL of JAK2 enzyme, 10 μM of poly (Glu,Ala,Tyr) substrate and 0.15 μM of ATP. For JAK3 assays, the reaction contained 3.5 μg/mL of JAK3 enzyme, 10 μM of poly (Glu,Ala,Tyr) substrate and 6.0 μM of ATP. For TYK2 assays, the reaction contained 2.5 μg/mL of TYK2 enzyme, 10 μM of poly (Glu,Ala,Tyr) substrate and 0.15 μM of ATP. The reaction is incubated at room temperature for 2 h prior to addition of 13 μL PKLight® detection reagent. After 10 min incubation luminescent signals are read on a multi-label plate reader.
細胞アッセイ 細胞株 Karpas 1106P cells
濃度 ~10 μM
反応時間 2 days
実験の流れ Cells are seeded at 30-50% confluency in 96-well plates and are treated with different concentrations of this compound (in triplicate) for 48 h. Cell viability is monitored using the CellTiter-Glo assay.
動物実験 動物モデル Human megakaryoblastic leukemia xenografts SET-2
投薬量 150 mg/kg
投与方法 oral gavage

参考

  • https://pubmed.ncbi.nlm.nih.gov/21691275/
  • https://pubmed.ncbi.nlm.nih.gov/22829080/

カスタマーフィードバック

Data from [Data independently produced by , , Clin Cancer Res, 2016, 22(24):6118-6128]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Pharmacological evaluation of drug therapies in Aicardi-Goutières syndrome: insights from patient-derived neural stem cells [ Front Pharmacol, 2025, 16:1549183] PubMed: 40183101
Inhibition of JAK2/STAT3 by pacritinib synergizes with chemotherapy in esophageal carcinoma [ Toxicol In Vitro, 2025, S0887-2333(25)00050-5] PubMed: 40112935
A living organoid biobank of patients with Crohn's disease reveals molecular subtypes for personalized therapeutics [ Cell Rep Med, 2024, 5(10):101748] PubMed: 39332415
Pacritinib inhibits proliferation of primary effusion lymphoma cells and production of viral interleukin-6 induced cytokines [ Sci Rep, 2024, 14(1):4125] PubMed: 38374336
Comprehensive profiling of clinical JAK inhibitors in myeloproliferative neoplasms [ Am J Hematol, 2023, 98(7):1029-1042] PubMed: 37203407
IRAK1 inhibition blocks the HIV-1 RNA mediated pro-inflammatory cytokine response from microglia [ J Gen Virol, 2023, 104(5)001858] PubMed: 37256770
TLR4 aggravates microglial pyroptosis by promoting DDX3X-mediated NLRP3 inflammasome activation via JAK2/STAT1 pathway after spinal cord injury [ Clin Transl Med, 2022, 12(6):e894] PubMed: 35692100
IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation [ Front Immunol, 2022, 13:1001068] PubMed: 36131914
Comprehensive drug response profiling and pan-omic analysis identified therapeutic candidates and prognostic biomarkers for Asian cholangiocarcinoma [ iScience, 2022, 25(10):105182] PubMed: 36248745
Cytochrome P450 27C1 Level Dictates Lung Cancer Tumorigenicity and Sensitivity towards Multiple Anticancer Agents and Its Potential Interplay with the IGF-1R/Akt/p53 Signaling Pathway [ Int J Mol Sci, 2022, 23(14)7853] PubMed: 35887201

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人間や獣医の診断であるか治療的な使用のためにでない。

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