Fedratinib

Summary

Fedratinib (CHEMBL1287853) is an approved small molecule (ATC L01EJ02) targeting BRD4, JAK1, and JAK2; indicated across 8 conditions including neoplasm and primary myelofibrosis; with CIViC clinical evidence for 1 variant-indication association (e.g. JAK2 V617F in polycythemia vera).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01EJ02
• Targets: 5 (BRD4, JAK1, JAK2…)
• Indications: 8 conditions
• Clinical trials: 27
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 524.7 Da · C27H36N6O3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1287853
Name	Fedratinib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	16722836
ATC	L01EJ02
Molecular formula	C27H36N6O3S
Molecular weight	524.7
InChIKey	JOOXLOJCABQBSG-UHFFFAOYSA-N

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

IUPAC name: N-tert-butyl-3-[[5-methyl-2-[4-(2-pyrrolidin-1-ylethoxy)anilino]pyrimidin-4-yl]amino]benzenesulfonamide

Also known as: Fedratinib, Sar-302503, SAR-302503, SAR302503, TG-101348, TG101348, SID137275863, FEDRATINIB, FEDRATINIB (SAR302503, TG101348), Fedratinib hydrochlorideÊ, Fedratinib (SAR302503; TG101348), Fedratinib hydrochlorideÂ

Parent form; salt/anhydrous children: CHEMBL4297216

Patent coverage: 1,383 distinct patent families (3,554 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 3,267 (92%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
BRD4	bromodomain containing 4	Inhibition	6.79	94.7% (common-essential)	O60885
JAK1	Janus kinase 1	Inhibition	7	2.8%	P23458
JAK2	Janus kinase 2	Inhibition	8.52	0.7%	O60674
JAK3	Janus kinase 3	Inhibition	6	0.6%	P52333
TYK2	tyrosine kinase 2	Inhibition	6.82	0.8%	P29597

Broader ChEMBL bioactivity targets: 303 (assay-derived). Sample: Leucine-rich repeat serine/threonine-protein kinase 2, Rhodopsin kinase GRK7, Serine/threonine-protein kinase 38, Homeodomain-interacting protein kinase 4, Serine/threonine-protein kinase TAO2, Serine/threonine-protein kinase/endoribonuclease IRE1, STE20/SPS1-related proline-alanine-rich protein kinase, Cyclin-dependent kinase-like 5, Mitogen-activated protein kinase kinase kinase 13, Bromodomain-containing protein 4.

Bioactivity

ChEMBL activities: 481 potent at pChembl ≥ 5 of 484 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
JAK2	9.12	IC50	0.75	nM	CHEMBL_ACT_22812644
GAK	9	IC50	1	nM	CHEMBL_ACT_24788450
JAK2	8.96	Kd	1.1	nM	CHEMBL_ACT_7576642
GAK	8.96	Kd	1.1	nM	CHEMBL_ACT_7578220
DAPK3	8.92	Kd	1.2	nM	CHEMBL_ACT_7576500
JAK2	8.54	IC50	2.89	nM	CHEMBL_ACT_28738913
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_14545501
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_16844151
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_18863592
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_24661608
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_24788498
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_25044282
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_25555221
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_25555222
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_25701596
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_25848284
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_25952280
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_26023215
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_26309189
JAK2	8.52	IC50	3	nM	CHEMBL_ACT_3605029
JAK2	8.51	IC50	3.08	nM	CHEMBL_ACT_28738907
JAK2	8.51	IC50	3.06	nM	CHEMBL_ACT_28738916
JAK2	8.5	IC50	3.16	nM	CHEMBL_ACT_28738910
JAK2	8.49	IC50	3.2	nM	CHEMBL_ACT_25659548
JAK2	8.49	IC50	3.24	nM	CHEMBL_ACT_28738919
JAK2	8.46	IC50	3.47	nM	CHEMBL_ACT_28738922
JAK2	8.37	Kd	4.3	nM	CHEMBL_ACT_25839819
FLT3	8.31	Kd	4.9	nM	CHEMBL_ACT_7576604
JAK2	8.22	IC50	6	nM	CHEMBL_ACT_24788455
JAK2	8.22	IC50	6	nM	CHEMBL_ACT_24861793

Target pathways

Aggregated over 5 target gene(s): BRD4, JAK1, JAK2, JAK3, TYK2.

Top Reactome pathways

87 total, by targets touching each:

Pathway	Targets	Genes
Potential therapeutics for SARS	5	BRD4, JAK1, JAK2, JAK3, TYK2
Disease	4	BRD4, JAK1, JAK2, JAK3
Infectious disease	4	BRD4, JAK1, JAK2, JAK3
Interleukin-4 and Interleukin-13 signaling	4	JAK1, JAK2, JAK3, TYK2
Interleukin-20 family signaling	4	JAK1, JAK2, JAK3, TYK2
SARS-CoV Infections	4	BRD4, JAK1, JAK2, JAK3
Viral Infection Pathways	4	BRD4, JAK1, JAK2, JAK3
Interleukin-6 signaling	3	JAK1, JAK2, TYK2
MAPK3 (ERK1) activation	3	JAK1, JAK2, TYK2
MAPK1 (ERK2) activation	3	JAK1, JAK2, TYK2
Cytokine Signaling in Immune system	3	JAK1, JAK2, JAK3
Signal Transduction	3	JAK1, JAK2, JAK3
Immune System	3	JAK1, JAK2, JAK3
Signaling by Interleukins	3	JAK1, JAK2, JAK3
Interleukin-2 family signaling	3	JAK1, JAK2, JAK3
Interleukin-3, Interleukin-5 and GM-CSF signaling	3	JAK1, JAK2, JAK3
RAF/MAP kinase cascade	3	JAK1, JAK2, JAK3
MAPK family signaling cascades	3	JAK1, JAK2, JAK3
MAPK1/MAPK3 signaling	3	JAK1, JAK2, JAK3
IL-6-type cytokine receptor ligand interactions	3	JAK1, JAK2, TYK2
Interleukin-35 Signalling	3	JAK1, JAK2, TYK2
Interleukin-12 signaling	3	JAK1, JAK2, TYK2
Interleukin-27 signaling	3	JAK1, JAK2, TYK2
Interleukin receptor SHC signaling	3	JAK1, JAK2, JAK3
Signaling by CSF3 (G-CSF)	3	JAK1, JAK2, TYK2
Inactivation of CSF3 (G-CSF) signaling	3	JAK1, JAK2, TYK2
Activation of STAT3 by cadherin engagement	3	JAK1, JAK2, TYK2
RAF-independent MAPK1/3 activation	2	JAK1, JAK2
Interleukin-7 signaling	2	JAK1, JAK3
Interleukin-12 family signaling	2	JAK1, JAK2

Dominant GO biological processes

GO term	Targets
protein phosphorylation	4
cell surface receptor signaling pathway via JAK-STAT	4
cytokine-mediated signaling pathway	4
cell differentiation	4
intracellular signal transduction	4
growth hormone receptor signaling pathway via JAK-STAT	4
regulation of cell-cell adhesion	4
regulation of transcription by RNA polymerase II	3
type II interferon-mediated signaling pathway	3
cellular response to virus	3
regulation of receptor signaling pathway via JAK-STAT	3
regulation of alpha-beta T cell activation	3
chromatin remodeling	2
positive regulation of transcription by RNA polymerase II	2
regulation of inflammatory response	2

Indications & clinical

Indications

8 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
neoplasm	4	MONDO:0005070	EFO:0000616
primary myelofibrosis	3	MONDO:0009692	EFO:0002430
myelodysplastic syndrome	2	MONDO:0018881	EFO:0000198
chronic neutrophilic leukemia	2	MONDO:0019451	EFO:1000179
liver disorder	1	MONDO:0005154	EFO:0001421
kidney disorder	1	MONDO:0005240	EFO:0003086

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 27.

Phase distribution

Phase	Trials
PHASE1	12
PHASE2	6
PHASE3	3
PHASE1/PHASE2	3
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01437787	PHASE3	COMPLETED	Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis
NCT03755518	PHASE3	TERMINATED	A Trial of Fedratinib in Subjects With DIPSS, Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib
NCT03952039	PHASE3	COMPLETED	An Efficacy and Safety Study of Fedratinib Compared to Best Available Therapy in Subjects With DIPSS-intermediate or High-risk Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib
NCT04282187	PHASE2	RECRUITING	Decitabine With Ruxolitinib, Fedratinib or Pacritinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms
NCT04446650	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of Fedratinib in Japanese Subjects With DIPSS (Dynamic International Prognostic Scoring System)- Intermediate or High-risk Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (Post-PV MF), or Post-essential Thrombocythemia Myelofibrosis (Post-ET MF)
NCT04817007	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Assess the Safety and Tolerability of BMS-986158 Alone and in Combination With Either Ruxolitinib or Fedratinib in Participants With Blood Cancer (Myelofibrosis)
NCT05177211	PHASE2	ACTIVE_NOT_RECRUITING	Fedratinib in Myelodysplastic /Myeloproliferative Neoplasms (MDS/MPNs) and Chronic Neutrophilic Leukemia (CNL)
NCT00724334	PHASE1/PHASE2	COMPLETED	A Long-Term Study of the Effects of Orally Administered SAR302503 in Patients With Myelofibrosis
NCT01420770	PHASE2	COMPLETED	Phase 2 Study of SAR302503 in Patients With Myelofibrosis
NCT01420783	PHASE2	COMPLETED	Study With SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia
NCT01523171	PHASE2	COMPLETED	Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib
NCT01692366	PHASE2	COMPLETED	Phase 2 Study in Japanese Patients With Intermediate-2 or High Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly
NCT00631462	PHASE1	COMPLETED	A Dose-escalation Study of the Safety and Tolerability of Orally Administered TG101348 in Patients With Myelofibrosis
NCT01585623	PHASE1	COMPLETED	Drug Interaction Study of SAR302503 in Patients With Solid Tumor
NCT01762462	PHASE1	COMPLETED	Open Label Pharmacokinetic Study of SAR302503 in Subjects With Hepatic Impairment
NCT01763190	PHASE1	COMPLETED	Open Label Pharmacokinetic Study of SAR302503 in Subjects With Renal Impairment
NCT01836705	PHASE1	COMPLETED	Effect of SAR302503 on ECG Activity in Patients With Solid Tumors
NCT03983161	PHASE1	COMPLETED	A Pharmacokinetics and Tolerability Study of Fedratinib in Subjects With Moderate and Severe Hepatic Impairment
NCT03983239	PHASE1	COMPLETED	Effect of Rifampin and Efavirenz on the Pharmacokinetics of Fedratinib in Healthy Adult Subjects
NCT04231435	PHASE1	COMPLETED	Influence of Fedratinib on the Pharmacokinetics of the Transporter Probe Substrates Digoxin, Rosuvastatin, and Metformin
NCT04702464	PHASE1	COMPLETED	A Study to Evaluate the Effect of a Dual CYP2C19 and CYP3A4 Inhibitor, Fluconazole, on the Pharmacokinetics of Fedratinib in Healthy Adult Subjects
NCT04955938	PHASE1	WITHDRAWN	A Study of Fedratinib With IDH Inhibition in Advanced-Phase, IDH-Mutated Ph-Negative Myeloproliferative Neoplasms
NCT05051553	PHASE1	COMPLETED	A Study to Evaluate the Bioavailability of Fedratinib When Administered in Different Ways to Healthy Adult Participants
NCT05127174	PHASE1	TERMINATED	Maintenance Fedratinib to Prevent Post-Transplant Relapse in Myeloproliferative Neoplasms
NCT03723148	Not specified	AVAILABLE	Individual Patient Compassionate Use of Fedratinib
NCT06073847	Not specified	RECRUITING	A Post-Marketing Surveillance Study to Assess the Safety of Fedratinib in Korean Patients With Myelofibrosis
NCT05883904	Not specified	UNKNOWN	Real World Evidence of Fedratinib Effectiveness in MF

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
JAK2 V617F	Polycythemia Vera	Sensitivity/Response	Fedratinib	CIViC D	EID20

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

150 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
DEUCRAVACITINIB	ChEMBL + PubChem	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
Pazopanib	ChEMBL + PubChem	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
RITLECITINIB	ChEMBL + PubChem	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
ABROCITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
BARICITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
FILGOTINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
MOMELOTINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
NINTEDANIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
PACRITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
PEFICITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
RUXOLITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
SUNITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
TOFACITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
UPADACITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3, TYK2
BREPOCITINIB	ChEMBL	Phase 3	JAK1, JAK2, JAK3, TYK2
DELGOCITINIB	ChEMBL	Phase 3	JAK1, JAK2, JAK3, TYK2
DOVITINIB	ChEMBL	Phase 3	JAK1, JAK2, JAK3, TYK2
ITACITINIB	ChEMBL	Phase 3	JAK1, JAK2, JAK3, TYK2
LESTAURTINIB	ChEMBL	Phase 3	JAK1, JAK2, JAK3, TYK2
AT-9283	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
ATINVICITINIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
AZD-1480	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
BMS-911543	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
CC-401	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
CERDULATINIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
DECERNOTINIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
GANDOTINIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
GOLIDOCITINIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
GUSACITINIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
IFIDANCITINIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
IZENCITINIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
NEZULCITINIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
NS-018	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
OCLACITINIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
R-406	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
ROPSACITINIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
SOLCITINIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
SU-014813	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
TOZASERTIB	ChEMBL	Phase 2	JAK1, JAK2, JAK3, TYK2
Afatinib	PubChem	Approved	JAK1, JAK2, JAK3, TYK2
Gefitinib	PubChem	Approved	JAK1, JAK2, JAK3, TYK2
Idelalisib	PubChem	Approved	JAK1, JAK2, JAK3, TYK2
Selumetinib	PubChem	Approved	JAK1, JAK2, JAK3, TYK2
dacomitinib	ChEMBL + PubChem	Phase 4 (approved)	JAK1, JAK3, TYK2
IMATINIB	ChEMBL + PubChem	Phase 4 (approved)	JAK1, JAK2, TYK2
AXITINIB	ChEMBL	Phase 4 (approved)	JAK2, JAK3, TYK2
BOSUTINIB	ChEMBL	Phase 4 (approved)	JAK2, JAK3, TYK2
CERITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3
DASATINIB	ChEMBL	Phase 4 (approved)	JAK2, JAK3, TYK2
ENTRECTINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK2, JAK3
ERLOTINIB	ChEMBL	Phase 4 (approved)	JAK2, JAK3, TYK2
ABIVERTINIB	ChEMBL	Phase 3	JAK1, JAK2, JAK3
ALVOCIDIB	ChEMBL	Phase 3	JAK2, JAK3, TYK2
DEFACTINIB	ChEMBL	Phase 3	JAK2, JAK3, TYK2
BMS-919373	ChEMBL	Phase 2	JAK2, JAK3, TYK2
CENISERTIB	ChEMBL	Phase 2	JAK2, JAK3, TYK2
LONDAMOCITINIB	ChEMBL	Phase 2	JAK1, JAK2, TYK2
belumosudil	PubChem	Approved	JAK2, JAK3, TYK2