TG101209
Modify Date: 2024-01-05 17:48:45
TG101209 structure
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Common Name | TG101209 | ||
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| CAS Number | 936091-14-4 | Molecular Weight | 509.667 | |
| Density | 1.3±0.1 g/cm3 | Boiling Point | 703.1±70.0 °C at 760 mmHg | |
| Molecular Formula | C26H35N7O2S | Melting Point | N/A | |
| MSDS | N/A | Flash Point | 379.0±35.7 °C | |
Use of TG101209TG101209 is a selective JAK2 inhibitor with IC50 of 6 nM, less potent to Flt3 and RET with IC50 of 25 nM and 17 nM, appr 30-fold selective for JAK2 than JAK3, and sensitive to JAK2V617F and MPLW515L/K mutations. |
| Name | N-tert-butyl-3-[[5-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]benzenesulfonamide |
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| Synonym | More Synonyms |
| Description | TG101209 is a selective JAK2 inhibitor with IC50 of 6 nM, less potent to Flt3 and RET with IC50 of 25 nM and 17 nM, appr 30-fold selective for JAK2 than JAK3, and sensitive to JAK2V617F and MPLW515L/K mutations. |
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| Related Catalog | |
| Target |
JAK2:6 nM (IC50) JAK3:169 nM (IC50) RET:17 nM (IC50) FLT3:25 nM (IC50) |
| In Vitro | TG101209 is an orally bioavailable, small molecule, ATP-competitive inhibitor towards several tyrosine kinases. TG101209 inhibits growth of Ba/F3 cells expressing JAK2V617F or MPLW515L mutations with an IC50 of 200 nM. In a human JAK2V617F-expressing acute myeloid leukemia cell line, TG101209 induces cell cycle arrest and apoptosis, and inhibits phosphorylation of JAK2V617F, STAT5 and STAT3. TG101209 suppresses growth of hematopoietic colonies from primary progenitor cells harboring JAK2V617F or MPL515 mutations[1]. TG101209 significantly reduces STAT5 phosphorylation without affecting the total amount of STAT5 protein[2]. TG101209 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 TG101209 abrogates BCR-JAK2 and STAT5 phosphorylation, decreases Bcl-xL expression and triggers apoptosis of transformed Ba/F3 cells[4]. |
| In Vivo | TG101209 (100 mg/kg) effectively prolongs the survival in JAK2V617F-induced disease (10 days). Compared with placebo-treated animals, TG101209-treated animals exhibit statistically significant, dose-dependent reduction in the circulating tumor cell burden at day +11 to 20%[1]. |
| Cell Assay | 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 inhibits proliferation by 50%. All experiments are done in triplicate and the results normalized to growth of untreated cells. |
| Animal Admin | Severe combined immunodeficiency (SCID) mice are intravenously injected with 10 times 106 sorted GFP-positive BaF/3 cells expressing JAK2V617F (Ba/F3-V617F-GFP). TG101209 is administered by oral gavage at the indicated doses beginning day +3 after tumor cell infusion and ending on day +20. On day +11 following tumor cell injection, 1 mL blood is collected by terminal cardiac bleeding from the mouse that receives vehicle, and 0.1 mL of blood is collected by non-lethal retro-orbital collection from each of the three six-mouse groups dosed with 10, 30 or 100 mg/kg b.i.d. (twice daily) of TG101209, and samples pooled within the dose groups. Blood mononuclear cells are isolated by a Ficoll cushion centrifugation method (600 RCF and 30 min). The isolated cells are subjected to FACS analysis to determine the percentage of GFP-positive tumor cells (that is, Ba/F3-V617F-GFP cells). |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 703.1±70.0 °C at 760 mmHg |
| Molecular Formula | C26H35N7O2S |
| Molecular Weight | 509.667 |
| Flash Point | 379.0±35.7 °C |
| Exact Mass | 509.257294 |
| PSA | 114.10000 |
| LogP | 2.46 |
| Vapour Pressure | 0.0±2.2 mmHg at 25°C |
| Index of Refraction | 1.622 |
| Storage condition | -20℃ |
| N-tert-butyl-3-(5-methyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-4-ylamino)benzenesulfonamide |
| Benzenesulfonamide, N-(1,1-dimethylethyl)-3-[[5-methyl-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-4-pyrimidinyl]amino]- |
| N-(1,1-DIMETHYLETHYL)-3-[[5-METHYL-2-[[4-(4-METHYL-1-PIPERAZINYL)PHENYL]AMINO]-4-PYRIMIDINYL]AMINO]BENZENESULFONAMIDE |
| 1M3 |
| Kinome_702 |
| 3-[(5-Methyl-2-{[4-(4-methyl-1-piperazinyl)phenyl]amino}-4-pyrimidinyl)amino]-N-(2-methyl-2-propanyl)benzenesulfonamide |
| TG101209 |