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Details

Stereochemistry ACHIRAL
Molecular Formula C27H36N6O3S
Molecular Weight 524.678
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FEDRATINIB

SMILES

CC1=CN=C(NC2=CC=C(OCCN3CCCC3)C=C2)N=C1NC4=CC=CC(=C4)S(=O)(=O)NC(C)(C)C

InChI

InChIKey=JOOXLOJCABQBSG-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Description

Fedratinib (SAR-302503, TG-101348) is a selective small-molecule inhibitor of Janus kinase-2. Fedratinib demonstrated therapeutic efficacy in a murine model of myeloproliferative disease. Sanofi was developing Fedratinib for the treatment of myeloproliferative diseases and solid tumors. The clinical development of fedratinib was terminated after reports of Wernicke's encephalopathy in myelofibrosis patients.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.0 nM [IC50]
Conditions
PubMed

PubMed

TitleDatePubMed
Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera.
2008 Apr
Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3.
2010 Dec 15
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
Flavanoids induce expression of the suppressor of cytokine signalling 3 (SOCS3) gene and suppress IL-6-activated signal transducer and activator of transcription 3 (STAT3) activation in vascular endothelial cells.
2013 Sep 1
Dual kinase-bromodomain inhibitors for rationally designed polypharmacology.
2014 Apr
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs.
2015 Jun
Patents

Sample Use Guides

In Vivo Use Guide
Fedratinib therapy in patients with primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF: once-daily oral fedratinib, at a dose of 400 mg or 500 mg, or placebo, for at least 6 consecutive 4-week cycles. Fedratinib therapy significantly reduced splenomegaly and symptom burden in patients with MF. These benefits were accompanied by toxic effects in some patients, the most important being encephalopathy of unknown mechanism. Clinical development of fedratinib was subsequently discontinued.
Route of Administration: Oral
In Vitro Use Guide
300 nM Fedratinib (SAR-302503, TG-101348) significantly inhibited JAK2V617F+ progenitor-derived colony formation
Name Type Language
FEDRATINIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
FEDRATINIB [INN]
Common Name English
BENZENESULFONAMIDE, N-(1,1-DIMETHYLETHYL)-3-((5-METHYL-2-((4-(2-(1-PYRROLIDINYL)ETHOXY)PHENYL)AMINO)-4-PYRIMIDINYL)AMINO)-
Systematic Name English
N-TERT-BUTYL-3-((5-METHYL-2-(4-(2-(PYRROLIDIN-1-YL)ETHOXY)ANILINO(PYRIMIDIN-4-YL)AMINO)BENZENESULFONAMIDE
Common Name English
N-TERT-BUTYL-3-(5-METHYL-2-(4-(2-PYRROLIDIN-1-YL-ETHOXY)-PHENYLAMINO)-PYRIMIDIN-4-YLAMINO)-BENZENESULFONAMIDE
Systematic Name English
SAR-302503
Code English
SAR302503
Code English
TG101348
Code English
TG-101348
Code English
FEDRATINIB [WHO-DD]
Common Name English
FEDRATINIB [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 23:18:56 UTC 2019 , Edited by admin on Mon Oct 21 23:18:56 UTC 2019
NCI_THESAURUS C125450
Created by admin on Mon Oct 21 23:18:56 UTC 2019 , Edited by admin on Mon Oct 21 23:18:56 UTC 2019
Code System Code Type Description
WIKIPEDIA
TG101348
Created by admin on Mon Oct 21 23:18:56 UTC 2019 , Edited by admin on Mon Oct 21 23:18:56 UTC 2019
PRIMARY
ChEMBL
CHEMBL1287853
Created by admin on Mon Oct 21 23:18:56 UTC 2019 , Edited by admin on Mon Oct 21 23:18:56 UTC 2019
PRIMARY
INN
9707
Created by admin on Mon Oct 21 23:18:56 UTC 2019 , Edited by admin on Mon Oct 21 23:18:56 UTC 2019
PRIMARY
EPA CompTox
936091-26-8
Created by admin on Mon Oct 21 23:18:56 UTC 2019 , Edited by admin on Mon Oct 21 23:18:56 UTC 2019
PRIMARY
NCI_THESAURUS
C88293
Created by admin on Mon Oct 21 23:18:56 UTC 2019 , Edited by admin on Mon Oct 21 23:18:56 UTC 2019
PRIMARY
CAS
936091-26-8
Created by admin on Mon Oct 21 23:18:56 UTC 2019 , Edited by admin on Mon Oct 21 23:18:56 UTC 2019
PRIMARY
EVMPD
SUB126288
Created by admin on Mon Oct 21 23:18:56 UTC 2019 , Edited by admin on Mon Oct 21 23:18:56 UTC 2019
PRIMARY
PUBCHEM
16722836
Created by admin on Mon Oct 21 23:18:56 UTC 2019 , Edited by admin on Mon Oct 21 23:18:56 UTC 2019
PRIMARY