Home JAK/STAT JAK inhibitor - FLT3 inhibitor - c-RET inhibitor - Apoptosis related activator Fedratinib (TG101348) For research use only.

Fedratinib (TG101348)

Synonyms: SAR302503

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. Fedratinib also inhibits FMS-like tyrosine kinase 3 (FLT3) and RET (c-RET) with IC50 of 15 nM and 48 nM, respectively. Fedratinib has potential antineoplastic activity. Fedratinib inhibits proliferation and induces apoptosis. Phase 2.

Fedratinib (TG101348) Chemical Structure

Fedratinib (TG101348) Chemical Structure

CAS No. 936091-26-8

Purity & Quality Control

Fedratinib (TG101348) Related Products

Signaling Pathway

JAK Signaling Pathways

JAK Signaling Pathway

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
MV4-11 Antiproliferative assay 72 hrs Antiproliferative activity against human MV4-11 cells after 72 hrs by celltiter-blue assay, EC50 = 0.079 μM. 28280261
MM1S Antiproliferative assay 72 hrs Antiproliferative activity against human MM1S cells after 72 hrs by trypan blue exclusion assay, IC50 = 1 μM. 28280261
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
Click to View More Cell Line Experimental Data

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. Fedratinib also inhibits FMS-like tyrosine kinase 3 (FLT3) and RET (c-RET) with IC50 of 15 nM and 48 nM, respectively. Fedratinib has potential antineoplastic activity. Fedratinib inhibits proliferation and induces apoptosis. 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
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]
Kinase Assay Cell-free Kinase Activity Assays
IC50 values for TG101348 are determined commercially using the InVitrogen kinase profiling service for a 223 kinase screen that included JAK2 and JAK2V617F or Carna Biosciences for the screen of all Janus kinase family members including JAK1 and Tyk2. ATP concentration is set to approximately the Km value for each kinase.
Cell Research Cell lines EpoBa/F3 JAK2V617F, Ba/F3p210, HEL, and K562
Concentrations Dissolved in DMSO, final concentrations ~10 μM
Incubation Time 72 hours
Method

Approximately 2 × 103 cells are plated into microtiter-plate wells in 100 μL RPMI-1640 growth media with indicated concentrations of inhibitor. Following 72 hours incubation with TG101348, 50 μL of XTT dye are added to each well and incubated for 4 hours in a CO2 incubator. The colored formazan product is measured by spectrophotometry at 450 nm with correction at 650 nm. The concentration in which 50% of the effect (i.e., inhibition of proliferation) is observed (IC50) is determined using the GraphPad Prism 4.0 software. All experiments are performed in triplicate, and the results are normalized to growth of untreated cells. Induction of apoptosis of EpoBa/F3 JAK2V617F, Ba/F3p210, HEL, and K562 cells is determined by DNA fragmentation with DMSO and increasing concentrations of TG101348.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-JAK2 / p-STAT1 / p-STAT3 / p-STAT6 / p-STAT5 / JAK2 c-Myc / PIM1 24610827
Growth inhibition assay Cell proliferation 24610827
In Vivo
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]
Animal Research Animal Models C57BL/6 mice injected intravenously with whole bone marrow expressing JAK2V617F
Dosages ~120 mg/kg
Administration Oral gavage twice daily (b.i.d.)
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04955938 Recruiting
IDH Mutation|IDH1 Mutation|IDH2 Gene Mutation|Blood Cancer|Myeloproliferative Neoplasm
University of Chicago
 October 29 2021 Phase 1
NCT05051553 Completed
Healthy Volunteers
Bristol-Myers Squibb
 September 21 2021 Phase 1
NCT04702464 Completed
Healthy Volunteers
Celgene|Impact Biomedicines Inc. a wholly owned subsidiary of Celgene Corporation
 January 12 2021 Phase 1
NCT03983161 Completed
Healthy Volunteers|Hepatic Impairment
Celgene|Impact Biomedicines Inc. a wholly owned subsidiary of Celgene Corporation
 September 4 2019 Phase 1
NCT03983239 Completed
Healthy Volunteers
Celgene|Impact Biomedicines Inc. a wholly owned subsidiary of Celgene Corporation
 June 21 2019 Phase 1

Chemical Information & Solubility

Molecular Weight 524.68 Formula

C27H36N6O3S
CAS No. 936091-26-8 SDF Download Fedratinib (TG101348) SDF
Smiles CC1=CN=C(N=C1NC2=CC(=CC=C2)S(=O)(=O)NC(C)(C)C)NC3=CC=C(C=C3)OCCN4CCCC4
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (190.59 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy Fedratinib (TG101348) | Fedratinib (TG101348) supplier | purchase Fedratinib (TG101348) | Fedratinib (TG101348) cost | Fedratinib (TG101348) manufacturer | order Fedratinib (TG101348) | Fedratinib (TG101348) distributor