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TG101348

Cat. No. M1733
TG101348 Structure
Synonym:

Fedratinib,SAR302503

Size Price Availability Quantity
10mg USD 120 In stock
50mg USD 350 In stock
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Quality Control
Biological Activity

TG101348 is a selective small-molecule Janus kinase 2 (JAK2) inhibitor with IC50 of 6 nM.TG-101348 also inhibits FLT3 and RET with IC50 values of 25 and 17 nM, respectively. In vivo, TG101348 exhibits promising pharmacokinetic profiles in species ranging from mouse to monkey including oral availabilities >20%, and half-lives consistent with once or twice daily dosing. TG101348 reduces the number of circulating mutant JAK2 cells, inhibited splenomegaly and improved survival without significantly impacting normal hematocrit in an aggressive JAK2-driven circulating cell model of disease in rodents.

Protocol
Cell Experiment
Cell lines EpoBa/F3 JAK2V617F, Ba/F3p210, HEL, and K562 cells
Preparation method XTT Assay for Cell Proliferation, Apoptosis, and DNA Laddering Assay Approximately 2 3 103 cells were plated into microtiter-plate wells in 100 ml RPMI-1640 growth media with indicated concentrations of inhibitor. Following 72 hr incubation with TG101348, 50 ml of XTT dye (Roche; Basel, Switzerland) were added to each well and incubated for 4 hr in a CO2 incubator. The colored formazan product was 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) was determined using the GraphPad Prism 4.0 software. All experiments were performed in triplicate, and the results were normalized to growth of untreated cells. Induction of apoptosis of EpoBa/F3 JAK2V617F, Ba/F3p210, HEL, and K562 cells was determined by DNA fragmentation with DMSO and increasing concentrations of inhibitor.
Concentrations 0~30µM
Incubation time 72h
Animal Experiment
Animal models The murine BM transplant model with C57BL/6 mice
Formulation saline
Dosages twice daily (b.i.d.) at 60 mg/kg, 120 mg/kg from day 28 on for 42 days
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 524.68
Formula C27H36N6O3S
CAS Number 936091-26-8
Purity 99.85%
Solubility DMSO
Storage at -20°C
Customer Product Validations & Biological Datas
Source Blood cancer journal (2016) . Figure 4. ruxolitinib (Abmole Bioscience, Houston, TX, USA) and fedratinib (Abmole Bioscience)
Method Western blotting
Cell Lines Embroys of wild-type zebrafish
Concentrations 1 μM ~ 8 μM
Incubation Time 24 h
Results The expression of CALRdel52 mRNA significantly increased stat5 phosphorylation (Figure 4a, lane 2). Furthermore, treatment with ruxolitinib and fedratinib significantly ameliorated the enhanced stat5 phosphorylation induced by CALR-del52 mRNA (Figure 4a, lane 3 and 4). In addition, treatment with ruxolitinib significantly decreased the numbers of CD41+ thrombocytes in uninjected control as well as CALR-del52-injected embryos in a dose-dependent manner (Figure 4b). Whereas treatment with fedratinib only had minimal inhibitory effect on the number of CD41+ thrombocytes in uninjected control embryos, and had a modest and significant dose-independent inhibitory effect on mutant CALR-induced thrombocytosis (Figure 4c). Our results demonstrated that mutant CALR-mediated pathogenic thrombopoiesis involves jak-stat activation that can be blocked by JAK inhibitors.
Rating
Product Citations
References

JAK2 inhibitors and their impact in myeloproliferative neoplasms.
Geyer HL et al. Hematology. 2012 Apr;17 Suppl 1:S129-32. PMID: 22507800.

Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis.
Pardanani A et al. J Clin Oncol. 2011 Mar 1;29(7):789-96. PMID: 21220608.

Inhibition of JAK-STAT signaling by TG101348: a novel mechanism for inhibition of KITD816V-dependent growth in mast cell leukemia cells.
Lasho T et al. Leukemia. 2010 Jul;24(7):1378-80. PMID: 20485374.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: TG101348, Fedratinib,SAR302503 supplier, JAK, inhibitors

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