Fedratinib hydrochloride hydrate
(Synonyms: TG-101348 hydrochloride hydrate; SAR 302503 hydrochloride hydrate) 目录号 : GC60161
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Fedratinib hydrochloride hydrate是一种有效、选择性、ATP竞争性且可口服的JAK2抑制剂，对JAK2和JAK2V617F激酶的IC50值均为3nM。
Cas No.:1374744-69-0
Sample solution is provided at 25 µL, 10mM.
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Fedratinib hydrochloride hydrate is an effective, selective, ATP competitive and orally active JAK2 inhibitor, and the IC50 values for both JAK2 and JAK2V617F kinases are 3nM[1]. Fedratinib hydrochloride hydrate inhibits the carrier-mediated uptake and transcellular flux of thiamine in cell[2]. Fedratinib hydrochloride hydrate has been widely used to inhibit the progression of solid tumors and as a model compound for developing new JAK target inhibitors[3].
In vitro, Fedratinib hydrochloride hydrate treatment for 48 hours significantly inhibited the viability of HMC-1.2 cells, with an IC50 value of 3.74µM[4]. Fedratinib hydrochloride hydrate treatment at 3μM for 10 days significantly inhibited the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSC-TERT) that overexpressed the human telomerase reverse transcriptase gene (TERT), resulting in a significant reduction in mineralized matrix formation and a decrease in the expression of JAK2, STAT5, and STAT3[5]. Treatment with 5µM of Fedratinib hydrochloride hydrate for 24 hours reduced the cell migration and invasion abilities of SKOV3 cells, and arrested the cell cycle at the G1 phase[6].
In vivo, Fedratinib hydrochloride hydrate was administered orally by gavage at a dose of 120mg/kg, twice daily for 42 days, which significantly improved the survival rate of a murine model of myeloproliferative disease induced by JAK2V617F mutation, and inhibited splenomegaly and erythrocytosis[7]. A single oral administration of Fedratinib hydrochloride hydrate (60mg/kg) for 24 hours significantly reduced the IFN-γ-induced STAT1 phosphorylation in the peritoneal macrophages of mice[8].
References:
[1] Talpaz M, Kiladjian J J. Fedratinib, a newly approved treatment for patients with myeloproliferative neoplasm-associated myelofibrosis[J]. Leukemia, 2021, 35(1): 1-17.
[2] Zhang Q, Zhang Y, Diamond S, et al. The Janus kinase 2 inhibitor fedratinib inhibits thiamine uptake: a putative mechanism for the onset of Wernicke’s encephalopathy[J]. Drug Metabolism and Disposition, 2014, 42(10): 1656-1662.
[3] Qiu Q, Chi F, Zhou D, et al. Exploration of Janus kinase (JAK) and histone deacetylase (HDAC) bispecific inhibitors based on the moiety of fedratinib for treatment of both hematologic malignancies and solid cancers[J]. Journal of Medicinal Chemistry, 2023, 66(8): 5753-5773.
[4] Makeeva A, Stivala S, Ratti E, et al. Fedratinib and gandotinib induce apoptosis and enhance the efficacy of tyrosine kinase inhibitors in human mast cells[J]. American Journal of Cancer Research, 2025, 15(1): 84.
[5] AlMuraikhi N, Alaskar H, Binhamdan S, et al. JAK2 inhibition by fedratinib reduces osteoblast differentiation and mineralisation of human mesenchymal stem cells[J]. Molecules, 2021, 26(3): 606.
[6] Dong Y, Deng Y, Zhu L, et al. Fedratinib inhibits ovarian cancer progression by downregulating QPCT expression[J]. Discover Oncology, 2025, 16(1): 1865.
[7] Wernig G, Kharas M G, Okabe R, et al. Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera[J]. Cancer cell, 2008, 13(4): 311-320.
[8] Keenan C, Albeituni S, Oak N, et al. Differential effects of itacitinib, fedratinib, and ruxolitinib in mouse models of hemophagocytic lymphohistiocytosis[J]. Blood, 2024, 143(23): 2386-2400.
Fedratinib hydrochloride hydrate是一种有效、选择性、ATP竞争性且可口服的JAK2抑制剂，对JAK2和JAK2V617F激酶的IC50值均为3nM[1]。Fedratinib hydrochloride hydrate可抑制细胞中硫胺素的载体介导摄取和跨细胞转运[2]。Fedratinib hydrochloride hydrate已被广泛用于抑制实体瘤的进展，并作为开发新型JAK靶点抑制剂的模型化合物[3]。
在体外，Fedratinib hydrochloride hydrate处理48小时显著抑制了HMC-1.2细胞的活力，IC50值为3.74µM[4]。使用3µM的Fedratinib hydrochloride hydrate处理10天，显著抑制了过表达人端粒酶逆转录酶基因（TERT）的人骨髓间充质干细胞（hBMSC-TERT）的成骨分化，导致矿化基质形成显著减少，并降低了JAK2、STAT5和STAT3的表达[5]。使用5µM的Fedratinib hydrochloride hydrate处理24小时，降低了SKOV3细胞的迁移和侵袭能力，并使细胞周期停滞在G1期[6]。
在体内，每日两次通过灌胃口服给予120mg/kg剂量的Fedratinib hydrochloride hydrate，持续42天，显著提高了由JAK2V617F突变诱导的骨髓增殖性疾病小鼠模型的存活率，并抑制了脾肿大和红细胞增多症[7]。单次口服60mg/kg剂量的Fedratinib hydrochloride hydrate 24小时，显著降低了小鼠腹腔巨噬细胞中IFN-γ诱导的STAT1磷酸化[8]。
| Cell experiment [1]: | |
Cell lines | hMSC-TERT cells |
Preparation Method | hMSC-TERT cells were cultured in Dulbecco's Modified Eagle Medium (DMEM), supplemented with 4500mg/l D-glucose, 4mM L-glutamine, 110mg/l 10% sodium pyruvate, 10% fetal bovine serum (FBS), 1% non-essential amino acids, and 1% penicillin-streptomycin. The incubator temperature was set at 37°C, humidity at 95%, and CO2 concentration at 5% to maintain cell growth. The cells were seeded in 96-well plates, with 300μl of culture medium added to each well, 30μM of Fedratinib hydrochloride hydrate were added. The control group cells were added with DMSO. After 72h, cell viability was analyzed. |
Reaction Conditions | 30μM; 72h |
Applications | Fedratinib hydrochloride hydrate treatment significantly decreased the cell viability of hMSC-TERT cells. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | The C57BL/6J mice were raised in a specific pathogen-free (SPF) animal facility and had free access to food and water. Administer a single oral dose of Fedratinib hydrochloride hydrate (60mg/kg) and intraperitoneal injection of 500ng of IFN-γ to the mice. Then, 24 hours later, detect the intracellular phosphorylation level of STAT1 in the peritoneal macrophages of the mice. |
Dosage form | 60mg/kg for once; p.o. |
Applications | Fedratinib hydrochloride hydrate treatment significantly decreased STAT1 phosphorylation within the peritoneal macrophages in mice. |
References: | |
| Cas No. | 1374744-69-0 | SDF | |
| 别名 | TG-101348 hydrochloride hydrate; SAR 302503 hydrochloride hydrate | ||
| Canonical SMILES | [H]Cl.[H]O[H].[H]Cl.O=S(C1=CC=CC(NC2=NC(NC3=CC=C(C=C3)OCCN4CCCC4)=NC=C2C)=C1)(NC(C)(C)C)=O | ||
| 分子式 | C27H40Cl2N6O4S | 分子量 | 615.62 |
| 溶解度 | DMSO: 250 mg/mL (406.09 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6244 mL | 8.1219 mL | 16.2438 mL |
| 5 mM | 324.9 μL | 1.6244 mL | 3.2488 mL |
| 10 mM | 162.4 μL | 812.2 μL | 1.6244 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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- Purity: >98.00% Appearance: A solid
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