1. Epigenetics
    Stem Cell/Wnt
    JAK/STAT Signaling
  2. JAK

Fedratinib (Synonyms: TG-101348; SAR 302503)

Cat. No.: HY-10409 Purity: 98.62%
Handling Instructions

Fedratinib (TG-101348) is a selective inhibitor of JAK2 with an IC50 of 3 nM, showing 35- and 334-fold selectivity over JAK1 and JAK3, respectively.

For research use only. We do not sell to patients.

Fedratinib Chemical Structure

Fedratinib Chemical Structure

CAS No. : 936091-26-8

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 111 In-stock
Estimated Time of Arrival: December 31
5 mg USD 96 In-stock
Estimated Time of Arrival: December 31
10 mg USD 132 In-stock
Estimated Time of Arrival: December 31
50 mg USD 384 In-stock
Estimated Time of Arrival: December 31
100 mg USD 600 In-stock
Estimated Time of Arrival: December 31
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    Fedratinib purchased from MCE. Usage Cited in: Mol Pharm. 2017 Jan 3;14(1):274-283.

    Effects of Ponatinib and SAR302503 combination on BCR-ABL1 kinase and related proteins activity in the existence of IL-3. Western blot analysis on Ponatinib and SAR302503 treated BaF3/T315I cells for 2 h and stimulated with IL-3 stimulation (5 ng/mL) for 15 min. BCR-ABL1 phosphorylation is inhibited by Ponatinib while JAK2 and STAT5 are reactivated in the presence of IL-3. This reactivation is inhibited by low concentration of SAR302503. Ponatinib and SAR302503 combination deeply inhibits JAK2

    Fedratinib purchased from MCE. Usage Cited in: IUBMB Life. 2018 Jan;70(1):81-91.

    A549 cells are treated with TG101348 (3 nM), BMS-911543 (1.5 nM), and Stattic (2.5 lM) for 24 h, and the conditioned media are collected and applied for tube formation assay in HUVECs.

    View All JAK Isoform Specific Products:

    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Fedratinib (TG-101348) is a selective inhibitor of JAK2 with an IC50 of 3 nM, showing 35- and 334-fold selectivity over JAK1 and JAK3, respectively.

    IC50 & Target

    JAK2

    3 nM (IC50)

    JAK2(V617F)

    3 nM (IC50)

    Flt3

    15 nM (IC50)

    Ret

    48 nM (IC50)

    In Vitro

    Fedratinib (TG-101348) significantly inhibits JAK2 V617F, Flt3, and Ret with IC50 of 3 nM, 15 nM, and 48 nM, respectively. TG101348 has an IC50 appr 300-fold higher for the closely related JAK3 and is a less potent inhibitor of the JAK1 and TYK2 family members. Fedratinib (TG-101348) inhibits proliferation of a human erythroblast leukemia (HEL) cell line that harbors the JAK2V617F mutation, as well as a murine pro-B cell line expressing human JAK2V617F (Ba/F3 JAK2V617F), with IC50 of 305 nM and 270 nM, respectively. Fedratinib (TG-101348) also inhibits proliferation of parental Ba/F3 cells to a comparable level, with IC50 of appr 420 nM. Fedratinib (TG-101348) treatment reduces STAT5 phosphorylation at concentrations that parallel the concentrations required to inhibit cell proliferation. Fedratinib (TG-101348) induces apoptosis in both HEL and Ba/F3 JAK2V617F cells in a dose-dependent manner. Fedratinib does not show proapoptotic activity in control normal human dermal fibroblasts at concentrations up to 10 μM, and the antiproliferative IC50 against fibroblasts is >5 μM[1]. Fedratinib (TG-101348) treatment decreases GATA-1 expression, which is associated with erythroid-skewing of JAK2V617F+ progenitor differentiation, and inhibits STAT5 as well as GATA S310 phosphorylation[2]. Fedratinib (TG-101348) inhibits the proliferation of HMC-1.1 (KITV560G) cells, with somewhat lower potency than HMC-1.2 (KITD816V, KITV560G) cells, with IC50 of 740 nM and 407 nM, respectively[3].

    In Vivo

    Fedratinib (TG-101348) has potential for efficacious treatment of JAK2V617F-associated myeloproliferative diseases (MPD). In treated animals, there is a statistically significant reduction in hematocrit and leukocyte count, a dose-dependent reduction/elimination of extramedullary hematopoiesis, and, at least in some instances, evidence for attenuation of myelofibrosis, correlated with surrogate endpoints, including reduction/elimination of JAK2V617F disease burden, suppression of endogenous erythroid colony formation, and in vivo inhibition of JAK-STAT signal transduction. There are no apparent toxicities and no effect on T cell number[1]. Oral administration of Fedratinib (TG-101348) (120 mg/kg) significantly inhibits PV progenitor erythroid differentiation in vivo[2].

    Clinical Trial
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 42 mg/mL (80.05 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.9059 mL 9.5296 mL 19.0592 mL
    5 mM 0.3812 mL 1.9059 mL 3.8118 mL
    10 mM 0.1906 mL 0.9530 mL 1.9059 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      TG-101348 (SAR302503) is dissolved in aqueous solution containing 30% polyethylene glycol 200/2% Tween 80[4].

    References
    Cell Assay
    [1]

    Approximately 2×103 cells are plated into microtiter-plate wells in 100 μL RPMI-1640 growth media with indicated concentrations of inhibitor. Following 72 hours incubation with Fedratinib, 50 μL of XTT dye are added to each well and incubated for 4 hours in a CO2 incubator. The colored formazan product is measured by spectrophotometry at 450 nm with correction at 650 nm. The concentration in which 50% of the effect (i.e., inhibition of proliferation) is observed (IC50) is determined using the GraphPad Prism 4.0 software. All experiments are performed in triplicate, and the results are normalized to growth of untreated cells. Induction of apoptosis of EpoBa/F3 JAK2V617F, Ba/F3p210, HEL, and K562 cells is determined by DNA fragmentation with DMSO and increasing concentrations of Fedratinib.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Briefly, C57BL/6 mice are intravenously injected with 1×106 whole bone marrow expressing JAK2V617F. Full development of disease is assessed with differential peripheral blood counts at day 26 after bone marrow transplantation. Fedratinib (TG-101348) is administered by oral gavage twice daily (b.i.d.) at 60 mg/kg, 120 mg/kg, or placebo from day 28 on for 42 days. Differential blood counts are assessed by retro-orbital nonlethal eyebleeds using EDTA glass capillary tubes before study initiation, during the study, and at study endpoints. C57/Bl6 mice are sacrificed at study endpoint or at times indicated based on an IUCAC-approved protocol that includes assessment of morbidity by > 10% loss of weight, scruffy appearance, lethargy, and/or splenomegaly extending across the midline. For histopathology, tissues are fixed in 10% neutral buffered formalin, embedded in paraffin, and stained with hematoxylin and eosinor, to assess for fibrosis, stained with reticulin.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    524.68

    Formula

    C₂₇H₃₆N₆O₃S

    CAS No.

    936091-26-8

    SMILES

    O=S(C1=CC=CC(NC2=NC(NC3=CC=C(C=C3)OCCN4CCCC4)=NC=C2C)=C1)(NC(C)(C)C)=O

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 98.62%

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    Cat. No.: HY-10409