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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|
((addition))-JQ1 is a BET bromodomain inhibitor, with IC50 of 77 nM/33 nM for BRD4(1/2).
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.
ARV-825 is a BRD4 inhibitor with DC50 (50% of maximum degradation) ＜1nM for Burkitt(acute)s lymphoma (BL) cell lines. Affinity to BD1 and BD2 of BRD4 by ARV-825 is 90 and 28 nM, respectively.
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.
BET-BAY 002 is a potent BET inhibitor; shows efficacy in a multiple myeloma model.
BET-IN-1 is a bromodomain inhibitor extracted from patent WO/2013024104A1, compound example 2, has a plC50 in the range 6.0 - 7.0.
BI2536 is a potent Plk1 inhibitor with IC50 of 0.83 nM, BI2536 shows 4- and 11-fold greater selectivity against Plk2 and Plk3; BI2536 also is a BRD4 inhibitor(IC50= 25 nM).
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.
Bromosporine is a broad spectrum inhibitor for bromodomains with IC50 of 0.41 (mu)M, 0.29 (mu)M, 0.122 (mu)M and 0.017 (mu)M for BRD2, BRD4, BRD9 and CECR2, respectively.
|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|