TG101209

Catalog No.S2692 Batch:S269201

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Technical Data

Formula

C26H35N7O2S
Molecular Weight 509.67 CAS No. 936091-14-4
Solubility (25°C)* In vitro DMSO 102 mg/mL (200.12 mM)
Water Insoluble
Ethanol Insoluble
In Vivo (Add solvents to the product individually and in order.)
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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description TG101209 is a selective JAK2 inhibitor with IC50 of 6 nM, less potent to FLT3 and RET (c-RET) with IC50 of 25 nM and 17 nM in cell-free assays, ~30-fold selective for JAK2 than JAK3, sensitive to JAK2V617F and MPLW515L/K mutations.
Targets
JAK2
(Cell-free assay)		 RET
(Cell-free assay)		 FLT3
(Cell-free assay)		 JAK3
(Cell-free assay)
6 nM 17 nM 25 nM 169 nM
In vitro TG101209 is an orally bioavailable, small molecule, ATP-competitive inhibitor towards several tyrosine kinases. This compound inhibits growth of Ba/F3 cells expressing JAK2V617F or MPLW515L mutations with an IC50 of B200 nM. In a human JAK2V617F-expressing acute myeloid leukaemia cell line, this chemical induces cell cycle arrest and apoptosis, and inhibits phosphorylation of JAK2V617F, STAT5 and STAT3. It suppresses growth of haematopoietic colonies from primary progenitor cells harbouring JAK2V617F or MPL515 mutations. This compound significantly reduces STAT5 phosphorylation without affecting the total amount of STAT5 protein. It inhibits survivin and reduces phosphorylation of STAT3 in HCC2429 and H460 lung cancer cells. TG101209 results in radio sensitisation of HCC2429 and H460 lung cancer cells in vitro. A recent study indicates this chemical abrogates BCR-JAK2 and STAT5 phosphorylation, decreases Bcl-xL expression and triggered apoptosis of transformed Ba/F3 cells.
In Vivo 100 mg/kg of TG101209 effectively prolongs the survival in JAK2V617F-induced disease (10 days). Compared with placebo-treated animals, this compound-treated animals exhibit statistically significant, dose-dependent reduction in the circulating tumour cell burden at day +11 to 20%.

Protocol (from reference)

Kinase Assay:[1]
  • Cell-free Kinase Activity Assays

    IC50 values for TG101209 are determined using a luminescence-based kinase assay with recombinant JAK2, VEGFR2/KDR, and JAK3 obtained from Upstate Cell Signaling Solutions. Kinase reactions are carried out in a buffer consisting of 40 mM Tris buffer (pH 7.4), 50 mM MgCl2, 800 µM EGTA, 350 µM Triton X-100, 2 µM β-mercaptoethanol, 100 µM peptide substrate, and an appropriate amount of JAK2, VEGFR2/KDR or JAK3 such that the assay is linear over 60 minutes. The reaction is initiated by the addition of 10 µL of ATP to a final concentration of 3 mM and terminated by the addition of Kinase-Glo reagent after 60 minutes. Luciferase activity is quantified using an Ultra 384 instrument set for luminosity measurements. IC50 values are derived from experimental data using the non-linear curve fitting capabilities of the GraphPad Prism 4.0 software. The single concentration inhibition data for a panel of 63 kinases is determined using the SelectScreen TM service.
Cell Assay:[1]
  • Cell Lines

    Ba/F3 cells expressing JAK2V617F (Ba/F3-EpoR-V617F) and MPLW515L (Ba/F3-W515L) mutants.

  • Concentrations

    4.6-38 400 nM

  • Incubation Time

    28-30 hours

  • Method

    In brief, approximately 2 × 103 cells are plated into microtiterplate wells in 100 ml RPMI-1640 growth media with indicated concentrations of TG101209. The relative growth of cells is quantified at 24-hour intervals using Cell Proliferation Kit II (XTT) as per manufacturer's guidelines. After incubation, 20 mL of XTT is added to the wells and allowed to incubate for 4-6 hours. The colored formazan product is measured spectrophotometrically at 450 nm with correction at 650 nm, and IC50 values are determined using the GraphPad Prism 4.0 software. Data are subjected to a non-linear regression-fit analysis and IC50 values are determined as the concentration that inhibited proliferation by 50%. All experiments are done in triplicate and the results normalized to growth of untreated cells.
Animal Study:[1]
  • Animal Models

    Ba/F3-V617F-GFP cells are injected into immunodeficient SCID mice to induce a rapidly fatal, fully penetrant hematopoietic disease.

  • Dosages

    100 mg/kg

  • Administration

    TG101209 is administered via oral gavage at the indicated doses beginning day +3 after tumor cell infusion and ending on day +20.

References

  • https://pubmed.ncbi.nlm.nih.gov/17541402/
  • https://pubmed.ncbi.nlm.nih.gov/19772888/
  • https://pubmed.ncbi.nlm.nih.gov/21325979/
  • https://pubmed.ncbi.nlm.nih.gov/22384256/
  • https://pubmed.ncbi.nlm.nih.gov/19828702/

Customer Product Validation

EGFR-ERCC1 effect on survival. QGP1 cells were transfected with Scrambled, ERCC1, EGFR, or EGFR-ERCC1 siRNA. Following 48 hours of siRNA transfection, Scrambled siRNA and ERCC1 siRNA-transfected cells were treated with 1 umol/L gefitinib or 125 nmol/L NU7026 (DNAPK inhibitor), or both, while EGFR siRNA and EGFR-ERCC1 siRNA-transfected cells were treated with 125 nmol/L of NU7026 1 hour prior 4 Gy IR treatment. Survival of these cells was then assessed 72 hours following IR treatment via MTT assay. The graphs show percentage of survival from 3 independent experiments as compared with untreated control. Bars show SD. Asterisks show statistical significance (*,P < 0.05; **, P < 0.01; ***, P < 0.001; NS, nonsignificant).

Data from [ Clin Cancer Res , 2014 , 20(13), 3496-506 ]

Primary plasma cells from MM patient 5 used were incubated with indicated concentrations of LCL161, TG101209 or the combination for 24 h. Western blot analysis were performed to examine expression levels of pStat3 and IAPs.

Data from [ Leukemia , 2014 , 28(7), 1519-28 ]

, , Claude HAAN Université du Luxembour

Sellecks TG101209 Has Been Cited by 20 Publications

Glucosidase alpha neutral C promotes influenza virus replication by inhibiting proteosome-dependent degradation of hemagglutinin [ Signal Transduct Target Ther, 2025, 10(1):131] PubMed: 40263249
System analysis of Huang-Lian-Jie-Du-Tang and their key active ingredients for overcoming CML resistance by suppression of leukemia stem cells [ Phytomedicine, 2023, 117:154918] PubMed: 37329755
Prediction of drug candidates for clear cell renal cell carcinoma using a systems biology-based drug repositioning approach [ EBioMedicine, 2022, 78:103963] PubMed: 35339898
IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation [ Front Immunol, 2022, 13:1001068] PubMed: 36131914
Canonical and noncanonical regulatory roles for JAK2 in the pathogenesis of rheumatoid arthritis-associated interstitial lung disease and idiopathic pulmonary fibrosis [ FASEB J, 2022, 36(6):e22336] PubMed: 35522243
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7] PubMed: 34997030
The JAK2 inhibitor TG101209 exhibits anti-tumor and chemotherapeutic sensitizing effects on Burkitt lymphoma cells by inhibiting the JAK2/STAT3/c-MYB signaling axis [ Cell Death Discov, 2021, 7(1):268] PubMed: 34588425
SWIM domain protein ZSWIM4 is required for JAK2 inhibition resistance in breast cancer [ Life Sci, 2021, 279:119696] PubMed: 34102191
Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment [ Cancer Sci, 2020, 112(1):133-143] PubMed: 33067904
TREM2 overexpression rescues cognitive deficits in APP/PS1 transgenic mice by reducing neuroinflammation via the JAK/STAT/SOCS signaling pathway [ Exp Neurol, 2020, S0014-4886(20)30337-X] PubMed: 33065077

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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