Fedratinib (SAR302503, TG101348) is a selective JAK2 inhibitor with an IC50 of 3 nM in cell-free trials and acts 35 and 334 times more selectively on JAK2 than on JAK1 and JAK3. Fedratinib also inhibits FMS-like tyrosine kinase 3 (FLT3) and Ret (c-RET) with corresponding IC50 values of 15 nM and 48 nM, respectively. Fedratinib has potential antitumor activity. Fedratinib can inhibit cell proliferation and promote apoptosis. Phase 2.

 

Brand: BCM

 

Target: Apoptosis; FLT; c-RET; JAK

 

Signaling Pathways: Angiogenesis; Apoptosis; Chromatin/Epigenetic; JAK/STAT signaling; Stem Cells; Tyrosine Kinase/Adaptors

 

In Vitro: Fedratinib (TG101348) inhibited 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 an IC50 value of approximately 300 nM for either line. Exposure of these cells to TG101348 reduced STAT5 phosphorylation at concentrations that parallel the concentrations required to inhibit cell proliferation. TG101348 inhibited the proliferation of HMC-1.1 (KITV560G) cells, with somewhat lower potency than HMC-1.2 (KITD816V, KITV560G) cells, with IC50's of 740 and 407 nM, respectively. TG101348 did not inhibit phosphorylation of KITV560G or KITD816V within the context of the two HMC-1 clones at concentrations up to 25 μM. TG101348 potently inhibited JAK-STAT signaling in HMC-1.2 cells, the IC50 for JAK2 phosphorylation was 150 and 600 nM; the IC50 for STAT-5 and STAT-3 phosphorylation was ~600 nM.

 

Melting Point: 180-182°C

 

Boiling Point: 713.7±70.0 °C(Predicted)

 

pKa: 11.95±0.50(Predicted)

 

Solubility: Soluble in DMSO. Insoluble in Water; Insoluble in Ethanol.

 

GHS: GHS07, GHS08

 

Isomeric SMILES: CC1=CN=C(N=C1NC2=CC(=CC=C2)S(=O)(=O)NC(C)(C)C)NC3=CC=C(C=C3)OCCN4CCCC4  

 

InChIKey: JOOXLOJCABQBSG-UHFFFAOYSA-N  

 

InChI: InChI=1S/C27H36N6O3S/c1-20-19-28-26(30-21-10-12-23(13-11-21)36-17-16-33-14-5-6-15-33)31-25(20)29-22-8-7-9-24(18-22)37(34,35)32-27(2,3)4/h7-13,18-19,32H,5-6,14-17H2,1-4H3,(H2,28,29,30,31)

 

Attribute
[Chem Name]	N-tert-butyl-3-[[5-methyl-2-[4-(2-pyrrolidin-1-ylethoxy)anilino]pyrimidin-4-yl]amino]benzenesulfonamide
[Synonym]	Fedratinib; TG101348; SAR302503
[CAS No.]	936091-26-8
[MDL No.]	MFCD12922515
[Formula]	C27H36N6O3S
[Molecular]	524.68
[Form]	Beige powder
[Storage]	Keep in dark place. Inert atmosphere. Store in freezer, under -20°C

Goods Tag