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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

Large-scale screening data

DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 3,7
Key to terms and symbols Click column headers to sort
Target Name in screen Sp. Type Action Value Parameter
cyclin G associated kinase GAK Hs Inhibitor Inhibition 9.0 pKd
Janus kinase 2 JAK2(JH1domain-catalytic) Hs Inhibitor Inhibition 9.0 pKd
death associated protein kinase 3 DAPK3 Hs Inhibitor Inhibition 8.9 pKd
fms related receptor tyrosine kinase 3 FLT3(D835H) Hs Inhibitor Inhibition 8.3 pKd
fms related receptor tyrosine kinase 3 FLT3(D835Y) Hs Inhibitor Inhibition 8.2 pKd
serine/threonine kinase 16 STK16 Hs Inhibitor Inhibition 8.2 pKd
doublecortin like kinase 3 DCAMKL3 Hs Inhibitor Inhibition 7.9 pKd
fms related receptor tyrosine kinase 3 FLT3 Hs Inhibitor Inhibition 7.9 pKd
fms related receptor tyrosine kinase 3 FLT3(K663Q) Hs Inhibitor Inhibition 7.9 pKd
death associated protein kinase 1 DAPK1 Hs Inhibitor Inhibition 7.8 pKd
Displaying the top 10 targets  View all targets in screen »