fedratinib   Click here for help

GtoPdb Ligand ID: 5716

Synonyms: Inrebic® | SAR302503 | TG-101348 | TG101348
Approved drug PDB Ligand
fedratinib is an approved drug (FDA (2019), EMA (2021))
Compound class: Synthetic organic
Comment: Fedratinib (TG‑101348) was initially reported as an orally active JAK2-FLT3 kinase inhibitor, with biological activity via JAK2 inhibition [6]. More recently, this compound has been discovered to function, in addition, as a BRD4 (bromodomain) inhibitor [2,4]. It is suggested that TG‑101348 be termed a dual kinase-bromodomain inhibitor. Fedratinib is been identified and officially approved as an alternative to the JAK1/2 inhibitor ruxolitinib for the treatment of primary and secondary myelofibrosis [1].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 8
Hydrogen bond donors 3
Rotatable bonds 11
Topological polar surface area 116.86
Molecular weight 524.26
XLogP 4.26
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES Cc1cnc(nc1Nc1cccc(c1)S(=O)(=O)NC(C)(C)C)Nc1ccc(cc1)OCCN1CCCC1
Isomeric SMILES Cc1cnc(nc1Nc1cccc(c1)S(=O)(=O)NC(C)(C)C)Nc1ccc(cc1)OCCN1CCCC1
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)
InChI Key JOOXLOJCABQBSG-UHFFFAOYSA-N
References
1. Bose P, Alfayez M, Verstovsek S. (2019)
New Concepts of Treatment for Patients with Myelofibrosis.
Curr Treat Options Oncol, 20 (1): 5. [PMID:30675650]
2. Ciceri P, Müller S, O'Mahony A, Fedorov O, Filippakopoulos P, Hunt JP, Lasater EA, Pallares G, Picaud S, Wells C et al.. (2014)
Dual kinase-bromodomain inhibitors for rationally designed polypharmacology.
Nat Chem Biol, 10 (4): 305-12. [PMID:24584101]
3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
4. Ember SW, Zhu JY, Olesen SH, Martin MP, Becker A, Berndt N, Georg GI, Schönbrunn E. (2014)
Acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts with diverse kinase inhibitors.
ACS Chem Biol, 9 (5): 1160-71. [PMID:24568369]
5. Malerich JP, Lam JS, Hart B, Fine RM, Klebansky B, Tanga MJ, D'Andrea A. (2010)
Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3.
Bioorg Med Chem Lett, 20 (24): 7454-7. [PMID:21106455]
6. Wernig G, Kharas MG, Okabe R, Moore SA, Leeman DS, Cullen DE, Gozo M, McDowell EP, Levine RL, Doukas J et al.. (2008)
Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera.
Cancer Cell, 13 (4): 311-20. [PMID:18394554]
7. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem Biol, 17 (11): 1241-9. [PMID:21095574]