Molecular Formula | C27H36N6O3S |
Molar Mass | 524.68 |
Density | 1.247 |
Melting Point | 180-182°C |
Boling Point | 713.7±70.0 °C(Predicted) |
Flash Point | 385.5 °C |
Solubility | DMSO (Slightly), Methanol (Slightly) |
Appearance | Beige powder. |
Color | White to Off-White |
pKa | 11.95±0.50(Predicted) |
Storage Condition | Keep in dark place,Inert atmosphere,Store in freezer, under -20°C |
In vitro study | TG-101348 also significantly inhibited JAK2 V617F, Flt3 and Ret,IC50 at 3 nM, 15 nM and 48 nM, respectively. TG101348 is more than 300 times higher than the IC50 of closely related JAK3, and has little inhibitory effect on JAK1 and TYK2 families. TG101348 inhibits the proliferation of a human erythroleukemia cell line with the JAK2V617F mutation and a mouse pre-B cell line expressing human JAK2V617F (Ba/F3 JAK2V617F) with IC50 of 305 nM and 270 nM, respectively. G-101348 also inhibited the proliferation of parental Ba/F3 cells to a normal level with an IC50 of about 420 nM. The concentration at which TG101348 reduced STAT5 phosphorylation was consistent with the concentration required to inhibit cell proliferation. TG101348 induced apoptosis of HEL and JAK2V617F Ba/F3 cells in a dose-dependent manner. TG101348 has no pro-apoptotic activity on normal human dermal fibroblasts at concentrations up to 10 μm. TG101348 reduced the expression of GATA-1, which and erythroid-skewing JAK2V617F TG101348 inhibited the proliferation of HMC-1.1(KITV560G) cells, the activity was lower than that of HMC-1.2 (KITD816V, KITV560G) cells, and the IC50 was 740 nM and 407 nM, respectively. |
In vivo study | TG101348 has the potential to treat jak2v617f-related myeloproliferative disorders (MPD). Statistically significant reductions in hematocrit and white blood cell counts in TG101348 treated animals, with a dose-dependent reduction/elimination of extramedullary hematopoiesis, at least in some cases, manifested by attenuating myelofibrosis, there are surrogate endpoints, including reduction/elimination of JAK2V617F disease burden, inhibition of endogenous erythrocyte colony formation associated with inhibition of JAK-STAT signaling in vivo. There was no apparent toxicity and no effect on T-cell numbers. Oral administration of TG101348(120 mg/kg) significantly inhibited photovoltaic erythroid progenitor cell differentiation in vivo. |
HS Code | 29350090 |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 1.906 ml | 9.53 ml | 19.059 ml |
5 mM | 0.381 ml | 1.906 ml | 3.812 ml |
10 mM | 0.191 ml | 0.953 ml | 1.906 ml |
5 mM | 0.038 ml | 0.191 ml | 0.381 ml |
biological activity | TG101348 (SAR302503) is a selective JAK2 inhibitor with an IC50 of 3 nM, the selectivity for JAK2 was 35 and 334-fold higher than for JAK1 and jak3. Phase 2. Fedratinib (SAR302503, TG101348) is a selective JAK2 inhibitor with an IC50 of 3 nM in a cell-free assay and is 35 and 334-fold more selective for JAK2 than JAK1 and jak3. Febatinib also inhibited FMS-like tyrosine kinase 3 (FLT3) and Ret (c-RET), corresponding to IC50 values of 15 nM and 48 nM, respectively. Febatinib has potential anti-tumor activity. Febatinib inhibits cell proliferation and promotes apoptosis. Phase 2. |
Target | Value |
JAK2 (Cell-free assay) | 3 nM |
JAK2 (V617F) (Cell-free assay) | 3 nM |
FLT3 (Cell-free assay) | 15 nM |
RET (Cell-free assay) | 48 nM |