Successful, we will reply to you quickly.OK
Please select the quantity.OK
Your message is being sent, please wait.Close
Send mail failed, please send again!Close
Products are for research use only. Not for human use. We do not sell to patients.
(Fedratinib; SAR 302503; TG101348; TG 101348)
TG-101348 Chemical Structure
|Product name: TG-101348|
|Cat. No.: HY-10409|
|ABT-263||≤1 nM, Ki||≤1 nM, Ki|
TG-101348 (SAR302503) is a selective inhibitor of JAK2 with IC50 of 3 nM, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3, TG-101348 also inhibit BRD4 with IC50 of 340 nM.
IC50 value: 3 nM (JAK2); 340 nM (BRD4)  
Target: JAK2; BRD4
in vitro: TG-101348 also significantly inhibits JAK2 V617F, Flt3, and Ret with IC50 of 3 nM, 15 nM, and 48 nM, respectively. TG101348 has an IC50 ~300-fold higher for the closely related JAK3 and is a less potent inhibitor of the JAK1 and TYK2 family members. TG101348 inhibits proliferation of a human erythroblast leukemia (HEL) cell line that harbors the JAK2V617F mutation, as well as a murine pro-B cell line expressing human JAK2V617F (Ba/F3 JAK2V617F), with IC50 of 305 nM and 270 nM, respectively. TG-101348 also inhibits proliferation of parental Ba/F3 cells to a comparable level, with IC50 of ~420 nM. TG101348 treatment reduces STAT5 phosphorylation at concentrations that parallel the concentrations required to inhibit cell proliferation. TG101348 induces apoptosis in both HEL and Ba/F3 JAK2V617F cells in a dose-dependent manner. TG101348 does not show proapoptotic activity in control normal human dermal fibroblasts at concentrations up to 10 μM, and the antiproliferative IC50 against fibroblasts is >5 μM . TG101348 treatment decreases GATA-1 expression, which is associated with erythroid-skewing of JAK2V617F+ progenitor differentiation, and inhibits STAT5 as well as GATA S310 phosphorylation . TG101348 inhibits the proliferation of HMC-1.1 (KITV560G) cells, with somewhat lower potency than HMC-1.2 (KITD816V, KITV560G) cells, with IC50 of 740 nM and 407 nM, respectively . TG101348 also is a inhibitor of BRD4 with IC50 of 340 nM .
in vivo: TG101348 has potential for efficacious treatment of JAK2V617F-associated myeloproliferative diseases (MPD). In treated animals, there is a statistically significant reduction in hematocrit and leukocyte count, a dose-dependent reduction/elimination of extramedullary hematopoiesis, and, t least in some instances, evidence for attenuation of myelofibrosis, correlated with surrogate endpoints, including reduction/elimination of JAK2V617F disease burden, suppression of endogenous erythroid colony formation, and in vivo inhibition of JAK-STAT signal transduction. There are no apparent toxicities and no effect on T cell number . Oral administration of TG101348 (120 mg/kg) significantly inhibits PV progenitor erythroid differentiation in vivo .
|M.Wt||524.68||Storage||Please store the product under the recommended conditions in the Certificate of Analysis.|
|Solvent & Solubility||
DMSO: ≥ 42 mg/mL
|1 mg||5 mg||10 mg|
|1 mM||1.9059 mL||9.5296 mL||19.0592 mL|
|5 mM||0.3812 mL||1.9059 mL||3.8118 mL|
|10 mM||0.1906 mL||0.9530 mL||1.9059 mL|
|Product Name||Sponsor Only||Condition||Start Date||End Date||Phase||Last Change Date|
|TG-101348||Sanofi||Polycythemia vera||30-NOV-12||30-JUN-14||Phase 2||09-NOV-13|
AG-490 (Tyrphostin AG 490) is an inhibitor of EGFR with IC50 of 0.1 (mu)M, 135-fold more selective for EGFR versus ErbB2, also inhibits JAK2 with no activity to Lck, Lyn, Btk, Syk and Src.
AT9283 is a small molecule a multi-targeted inhibitor with IC50s of 4, 1.2, 1.1 and approximate 3 nM for Bcr-Abl(T3151), JAK2 and JAK3, Aurora A and Aurora B, respectively.
AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1.
BMS-911543 is a potent and selective small-molecule inhibitor of JAK2, displays potent anti-proliferative and pharmacodynamic (PD) effects in cell lines dependent upon JAK2 signaling.
CEP-33779 is a novel, selective, and orally bioavailable inhibitor of JAK2 with IC50 of 1.8 nM.
Cerdulatinib(PRT-062070; PRT2070) is an novel oral dual Syk/JAK inhibitor.
Decernotinib(VX-509; VRT-831509) is a potent and selective Janus kinase 3 (JAK3) inhibitor with Ki of 2.5 nM; IC50 is 50-170 nM in cellular assays.
GLPG0634(filgotinib) is a selective JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM, and 116 nM for JAK1, JAK2, JAK3, and TYK2, respectively.
Itacitinib (INCB039110) is an oral selective JAK1 inhibitor.
JAK3-IN-1 is a potent JAK3 inhibitor with IC50 of 4.8 nM, also inhibits JAK1 (IC50 = 896 nM) and JAK2 (IC50 = 1050 nM).
|Compound Name||Bcl-2||Bcl-B||Bcl-w||Bcl-xL||Mcl-1||Bfl-1||Other target||Note|
|ABT-737||30.3 nM||78.7 nM||197.8 nM|
|ABT-263||≤1 nM, Ki||≤1 nM, Ki||≤0.5 nM, Ki|
|Obatoclax||3 uM||2.9 uM||5 uM|
|TW-37||290 nM Ki||1110 nM, Ki||360 nM, Ki|
|ABT-199||10 nM, Ki||>10 uM, Ki||>10 uM, Ki||No inhibition||Bcl-2 selective|
|AT101||320 nM, Ki||480 nM, Ki||180 nM, Ki|
|Gambogic Acid||1.21 uM||0.66 uM||2.02 uM||1.47 uM||0.79 uM||1.06 uM||Caspase|
|(+)-Apogossypol||0.5-2 uM||0.5-2 uM||0.5-2 uM||0.5-2 uM||0.5-2 uM||No inhibition|
|Mcl1-IN-1||No inhibition||2.4 uM||Mcl1 selective|
|MIM1||>50 uM||4.8 uM||Mcl1 selective|
|Pyridoclax||25 nM, Kd|