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TG101209 JAK inhibitor

Name: TG101209
Brand: Selleck Chemicals
SKU: S2692
Availability: InStock
Rating: 5 (20 reviews)

Cat.No.S2692

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.

Chemical Structure

Molecular Weight: 509.67

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.74%

99.74

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Chemical Information, Storage & Stability

Molecular Weight	509.67	Formula	C₂₆H₃₅N₇O₂S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	936091-14-4	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1=CN=C(N=C1NC2=CC(=CC=C2)S(=O)(=O)NC(C)(C)C)NC3=CC=C(C=C3)N4CCN(CC4)C

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (196.2 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5mg/ml (9.81mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.71mg/ml (1.39mM)	Taking the 1 mL working solution as an example, add 50 μL of 14.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
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.
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.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	JAK2 ^[1] (Cell-free assay) 6 nM RET ^[1] (Cell-free assay) 17 nM FLT3 ^[1] (Cell-free assay) 25 nM JAK3 ^[1] (Cell-free assay) 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 leukemia cell line, this chemical inducs cell cycle arrest and apoptosis, and inhibits phosphorylation of JAK2V617F, STAT5 and STAT3. It suppresses growth of hematopoietic colonies from primary progenitor cells harboring JAK2V617F or MPL515 mutations. ^[1] This compound significantly reduces STAT5 phosphorylation without affecting the total amount of STAT5 protein. ^[2] It inhibits survivin and reduces phosphorylation of STAT3 in HCC2429 and H460 lung cancer cells. TG101209 results in radio sensitization of HCC2429 and H460 lung cancer cells in vitro. ^[3] A recent study indicates this chemical abrogates BCR-JAK2 and STAT5 phosphorylation, decreases Bcl-xL expression and triggered apoptosis of transformed Ba/F3 cells. ^[4]
Kinase Assay	Cell-free Kinase Activity Assays
Kinase Assay	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 40mM Tris buffer (pH 7.4), 50mM MgCl₂, 800M EGTA, 350M Triton X-100, 2M -mercaptoethanol, 100M 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L of ATP to a final concentration of 3mM 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.
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 tumor cell burden at day +11 to 20%. ^[1]
References	[1] https://pubmed.ncbi.nlm.nih.gov/17541402/ [2] https://pubmed.ncbi.nlm.nih.gov/19772888/ [3] https://pubmed.ncbi.nlm.nih.gov/21325979/ [4] https://pubmed.ncbi.nlm.nih.gov/22384256/ [5] https://pubmed.ncbi.nlm.nih.gov/19828702/

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