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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
TG101209 is a novel, potent, orally bioactive and selective small molecule JAK2 inhibitor with IC50 of 6 nM. TG101209 has an IC50 of 6 nM. It is about 30 times more selective for JAK2 than JAK3 and is sensitive to the JAK2V617F and MPLW515L/K mutations. It is less potent to Flt3 and RET with IC50 values of 25 nM and 17 nM in cell-free assays. In numerous multiple myeloma (MM) cell lines, it caused cytotoxicity that was dose- and time-dependent. TG101209 exhibits anticancer properties.
| Targets |
JAK2 (IC50 = 6 nM); JAK3 (IC50 = 169 nM); RET (IC50 = 17 nM); FLT3 (IC50 = 25 nM)
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| ln Vitro |
TG101209 is an orally bioavailable, small molecule, ATP-competitive inhibitor towards several tyrosine kinases. TG101209 has an IC50 of 200 nM and inhibits the growth of Ba/F3 cells expressing JAK2V617F or MPLW515L mutations. TG101209 induces cell cycle arrest and apoptosis in a human acute myeloid leukemia cell line expressing JAK2V617F, and it prevents JAK2V617F, STAT5 and STAT3 from being phosphorylated. Primary progenitor cells with JAK2V617F or MPL515 mutations grow hematopoietic colonies less quickly when TG101209 is present.[1] Without changing the total amount of STAT5 protein, TG101209 significantly lowers STAT5 phosphorylation. [2] In HCC2429 and H460 lung cancer cells, TG101209 inhibits survivin and lowers the phosphorylation of STAT3. Lung cancer cells HCC2429 and H460 become radiosensitive in vitro when exposed to TG101209.[3] According to a recent study, TG101209 suppresses BCR-JAK2 and STAT5 phosphorylation, lowers Bcl-xL expression, and induces apoptosis in transformed Ba/F3 cells.[4]
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| ln Vivo |
In a JAK2V617F-induced disease, 100 mg/kg of TG101209 significantly extends survival (10 days). Statistically significant, dose-dependent reductions in the circulating tumor cell burden of up to 20% are seen in TG101209-treated animals at day +11 compared to animals that received a placebo. [1]
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| Enzyme 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 conducted in a buffer containing 40 mM Tris buffer (pH 7.4), 50 mM MgCl2, 800 mM EGTA, 350 mM Triton X-100, 2 mM -mercaptoethanol, 100 mM peptide substrate, and an adequate concentration of JAK2, VEGFR2/KDR, or JAK3 to ensure that the assay is linear over 60 minutes. After 60 minutes, Kinase-Glo reagent is added to end the reaction, which was started by the addition of 10 L of ATP to a 3 mM final concentration. An Ultra 384 instrument set for luminosity measurements is used to measure luciferase activity.
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| Cell Assay |
In brief, the indicated TG101209 concentrations are added to 100 ml of RPMI-1640 growth media, and 2 × 103 cells are plated into microtiterplate wells. Using the Cell Proliferation Kit II (XTT) in accordance with the manufacturer's instructions, the relative growth of cells is measured every 24 hours. 4-6 hours of incubation follow the addition of 20 mL of XTT to the wells. With correction at 650 nm, the colored formazan product is measured spectrophotometrically at 450 nm, and IC50 values are calculated using the GraphPad Prism 4.0 program. The concentration (IC50) that inhibited proliferation by 50% was found after the data were subjected to a non-linear regression-fit analysis. The results of each experiment are normalized to the growth of untreated cells and performed in triplicate.
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| Animal Protocol |
The GFP-positive BaF/3 cells expressing JAK2V617F (Ba/F3-V617F-GFP) are sorted and administered intravenously to SCID mice (severe combined immunodeficiency). On day +3 following the infusion of tumor cells and continuing until day +20, TG101209 is given by oral gavage at the indicated doses. On day +11 after tumor cell injection, 1 mL of blood is taken by terminal cardiac bleeding from the mouse that receives the vehicle, and 0.1 mL of blood is taken by non-lethal retro-orbital collection from each of the three groups of six mice that received doses of 10, 30, or 100 mg/kg (twice daily) of TG101209, with samples combining within the dose groups. With 600 RCF and 30 minutes of centrifugation, blood mononuclear cells are separated using the Ficoll cushion technique. FACS analysis is used to calculate the proportion of GFP-positive tumor cells in the isolated cells(that is, Ba/F3-V617F-GFP cells).
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| References | |
| Additional Infomation |
TG101209 is a member of the class of pyrimidines that is 5-methylpyrimidine-2,4-diamine in which the amino group at position 2 is substituted by a p-(4-methylpiperazin-1-yl)phenyl group, while that at position 4 is substituted by a m-(tert-butylsulfamoyl)phenyl group. A Janus kinase 2 (JAK2) inhibitor. It has a role as an EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor, an apoptosis inducer and an antineoplastic agent. It is a sulfonamide, a member of pyrimidines, a N-alkylpiperazine, a N-arylpiperazine and a secondary amino compound.
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| Molecular Formula |
C26H35N7O2S
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| Molecular Weight |
509.67
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| Exact Mass |
509.257
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| Elemental Analysis |
C, 61.27; H, 6.92; N, 19.24; O, 6.28; S, 6.29
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| CAS # |
936091-14-4
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| Related CAS # |
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| PubChem CID |
16722832
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| Appearance |
white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
703.1±70.0 °C at 760 mmHg
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| Flash Point |
379.0±35.7 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.622
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| LogP |
2.46
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
36
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| Complexity |
783
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=S(C1C=C(NC2C(C)=CN=C(NC3C=CC(N4CCN(C)CC4)=CC=3)N=2)C=CC=1)(NC(C)(C)C)=O
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| InChi Key |
JVDOKQYTTYUYDV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H35N7O2S/c1-19-18-27-25(29-20-9-11-22(12-10-20)33-15-13-32(5)14-16-33)30-24(19)28-21-7-6-8-23(17-21)36(34,35)31-26(2,3)4/h6-12,17-18,31H,13-16H2,1-5H3,(H2,27,28,29,30)
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| Chemical Name |
N-tert-butyl-3-[[5-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]benzenesulfonamide
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| Synonyms |
TG 101209; TG-101209; TG101209
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (5.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (5.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 1% DMSO +30% polyethylene glycol+1% Tween 80 : 12mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9621 mL | 9.8103 mL | 19.6205 mL | |
| 5 mM | 0.3924 mL | 1.9621 mL | 3.9241 mL | |
| 10 mM | 0.1962 mL | 0.9810 mL | 1.9621 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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