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TG101348

(CAS No:936091-26-8)
Fedratinib (SAR302503, TG101348) is a selective inhibitor of JAK2 with IC50 of 3 nM in cell-free assays, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. Phase 2.
CAS No:936091-26-8
Molecular Weight(MW):524.68
Purity:99.00%
Specification:500MG;1G;5G;10G;50G;100G
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QC Documents
　COA 　MSDS 　HPLC 　NMR
ChemicalInfomation
CAS No: 936091-26-8
Molecular formula(MF) C27H36N6O3S
Molecular Weight(MW): 524.68
Alias
Solubility
In vitro DMSO 100 mg/mL (190.59 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 1% DMSO+30% polyethylene glycol+1% Tween 80 30 mg/mL
Biological Activity
Description Fedratinib (SAR302503, TG101348) is a selective inhibitor of JAK2 with IC50 of 3 nM in cell-free assays, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. Phase 2.
Targets
JAK2 [1]
(Cell-free assay)		 JAK2 (V617F) [1]
(Cell-free assay)		 FLT3 [1]
(Cell-free assay)		 RET [1]
(Cell-free assay)
3 nM 3 nM 15 nM 48 nM
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. [1] 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. [2] 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. [3]
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
H1975 Apoptosis Assay 0.5-2 μM 12-48 h DMSO induces apoptosis in both dose- and time- dependent manner 25869210
H1650 Apoptosis Assay 0.5-2 μM 12-48 h DMSO induces apoptosis in both dose- and time- dependent manner 25869210
H1975 Function Assay 0.25-1 μM 24 h DMSO inhibits expression of apoptosis-related protein Bcl-XL, Bcl-2, survivin, XIAP 25869210
H1650 Function Assay 0.25-1 μM 24 h DMSO inhibits expression of apoptosis-related protein Bcl-XL, Bcl-2, survivin, XIAP 25869210
H1975 Growth Inhibition Assay 1 μM 48 h DMSO sensitizes cells to the cytotoxicity of erlotinib 25869210
H1650 Growth Inhibition Assay 1 μM 48 h DMSO sensitizes cells to the cytotoxicity of erlotinib 25869210
CD4+ T Function Assay 0.01-1 μM 48 h DMSO reduces the phosphorylation levels of JAK2 and STAT3  25572535
Caco-2  Function Assay 0-120 μM 7 min inhibits thiamine uptake with an IC50 of 2.1 µM 25063672
Caco-2  Function Assay 10/50/100 μM 2 h decreases the flux of [3H]thiamine across the monolayer with IC50 of 6.5 μM 25063672
HEK293 MSR  Function Assay 0-10 μM 7 min inhibits hTHTR2 with an IC50 of 1.2 µM 25063672
MedB-1 Function Assay 1/2 μM 24 h decreases STAT6 phosphorylation concentration dependently 24977668
U2940 Function Assay 1/2 μM 24 h decreases STAT6 phosphorylation concentration dependently 24977668
K1106 Function Assay 1/2 μM 24 h decreases STAT6 phosphorylation concentration dependently 24977668
K562 Growth Inhibition Assay 0-1 μM 72 h inhibits K562 cell proliferation at high concentration 24775308
MDA-MB-468  Growth Inhibition Assay 3 µM 48 h enhanced sibcl6 induced loss of cell viability  24662818
MDA-MB-468 Growth Inhibition Assay 0-4 μM 48 h results significant loss of viability compared to RI-BPI alone 24662818
L428 Growth Inhibition Assay 0-5 μM 48 h inhibits cell growth significantly 24610827
KMH2 Growth Inhibition Assay 0-5 μM 48 h inhibits cell growth significantly 24610827
L1236 Growth Inhibition Assay 0-5 μM 48 h inhibits cell growth significantly 24610827
SUPHD1 Growth Inhibition Assay 0-5 μM 48 h inhibits cell growth significantly 24610827
HDLM2 Growth Inhibition Assay 0-5 μM 48 h inhibits cell growth significantly 24610827
K1106P Growth Inhibition Assay 0-5 μM 48 h inhibits cell growth significantly 24610827
L428 Apoptosis Assay 0/0.625/1.25 μM 48 h induces the apoptosis  24610827
KMH2 Apoptosis Assay 0/0.625/1.25 μM 48 h induces the apoptosis  24610827
L1236 Apoptosis Assay 0/0.625/1.25 μM 48 h induces the apoptosis  24610827
SUPHD1 Apoptosis Assay 0/0.625/1.25 μM 48 h induces the apoptosis  24610827
HDLM2 Apoptosis Assay 0/0.625/1.25 μM 48 h induces the apoptosis  24610827
K1106P Apoptosis Assay 0/0.625/1.25 μM 48 h induces the apoptosis  24610827
L428 Function Assay 0-5 μM 24 h inhibits JAK2/STAT signaling 24610827
KMH2 Function Assay 0-5 μM 24 h inhibits JAK2/STAT signaling 24610827
L1236 Function Assay 0-5 μM 24 h inhibits JAK2/STAT signaling 24610827
SUPHD1 Function Assay 0-5 μM 24 h inhibits JAK2/STAT signaling 24610827
HDLM2 Function Assay 0-5 μM 24 h inhibits JAK2/STAT signaling 24610827
K1106P Function Assay 0-5 μM 24 h inhibits JAK2/STAT signaling 24610827
MM.1S  Growth Inhibition Assay IC50=1-3 μM 24584101
TpoR JAK2 WT Growth Inhibition Assay IC50=1.4 (1.3–1.5) μM 24251790
TpoR JAK2 V617F Growth Inhibition Assay IC50=0.8 (0.7–0.9) μM 24251790
TpoR W515L Growth Inhibition Assay IC50=0.8 (0.7–1.0) μM 24251790
Bcr-abl Growth Inhibition Assay IC50=2.7 (2.2–3.3) μM 24251790
JAK2 TW Growth Inhibition Assay IC50=1.8 (1.5–2.3) μM 24251790
JAK2 V617F Growth Inhibition Assay IC50=0.6 (0.6–0.7) μM 24251790
MedB-1 Growth Inhibition Assay 4 μM 24/48/72 h DMSO inhibits cell growth time dependently 23852366
K1106 Growth Inhibition Assay 4 μM 24/48/72 h DMSO inhibits cell growth time dependently 23852366
U2940 Growth Inhibition Assay 4 μM 24/48/72 h DMSO inhibits cell growth time dependently 23852366
FE-PD Growth Inhibition Assay 0.063-4 μM IC50=9.5 μM, inhibits cell growth dose dependently 23372669
HEL Growth Inhibition Assay 0.063-4 μM IC50=1.5 μM, inhibits cell growth dose dependently 23372669
K-562 Growth Inhibition Assay 0.063-4 μM IC50=2.5 μM, inhibits cell growth dose dependently 23372669
L-82 Growth Inhibition Assay 0.063-4 μM IC50=0.98 μM, inhibits cell growth dose dependently 23372669
MAC-1 Growth Inhibition Assay 0.063-4 μM IC50=0.52 μM, inhibits cell growth dose dependently 23372669
MAC-2A Growth Inhibition Assay 0.063-4 μM IC50=0.69 μM, inhibits cell growth dose dependently 23372669
MAC-2B Growth Inhibition Assay 0.063-4 μM IC50=0.54 μM, inhibits cell growth dose dependently 23372669
MY-LA Growth Inhibition Assay 0.063-4 μM IC50=2.1 μM, inhibits cell growth dose dependently 23372669
NC-NC Growth Inhibition Assay 0.063-4 μM IC50=1.0 μM, inhibits cell growth dose dependently 23372669
SE-AX Growth Inhibition Assay 0.063-4 μM IC50=1.5 μM, inhibits cell growth dose dependently 23372669
SR-786 Growth Inhibition Assay 0.063-4 μM IC50=4.6 μM, inhibits cell growth dose dependently 23372669
M-MOK  Growth Inhibition Assay 25 µM  24/48/72 h DMSO inhibits cell growth time dependently 21853157
HEL Growth Inhibition Assay IC50=305 nM 18394554
Ba/F3 JAK2V617F Growth Inhibition Assay IC50=270 nM 18394554

... Click to View More Cell Line Experimental Data
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, at 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. [1] Oral administration of TG101348 (120 mg/kg) significantly inhibits PV progenitor erythroid differentiation in vivo. [2]
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