pexidartinib   Click here for help

GtoPdb Ligand ID: 8710

Synonyms: PLX-3397 | PLX3397 | Turalio®
Approved drug PDB Ligand
pexidartinib is an approved drug (FDA (2019))
Compound class: Synthetic organic
Comment: Pexidartinib is an orally available, multi-targeted inhibitor of the receptor tyrosine kinases, Fms-related tyrosine kinase 3 (FLT3), stem cell growth factor receptor (KIT) and colony stimulating factor 1 receptor (CSF1R), with potential antineoplastic activity [5]. Pexidartinib is compound P-0181 in patent US7893075 B2 [6].
It is active against wild type FLT3 and the FLT3 gatekeeper F691L resistance mutant, but its activity is vulnerable to mutations in the FLT3 activation loop [4].
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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

pexidartinib is commercially available from our sponsors

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 4
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 66.49
Molecular weight 417.1
XLogP 4.58
No. Lipinski's rules broken 0

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 Clc1cnc2c(c1)c(c[nH]2)Cc1ccc(nc1)NCc1ccc(nc1)C(F)(F)F
Isomeric SMILES Clc1cnc2c(c1)c(c[nH]2)Cc1ccc(nc1)NCc1ccc(nc1)C(F)(F)F
InChI InChI=1S/C20H15ClF3N5/c21-15-6-16-14(10-28-19(16)29-11-15)5-12-2-4-18(26-7-12)27-9-13-1-3-17(25-8-13)20(22,23)24/h1-4,6-8,10-11H,5,9H2,(H,26,27)(H,28,29)
InChI Key JGWRKYUXBBNENE-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/)
References
1. Cupp JS, Miller MA, Montgomery KD, Nielsen TO, O'Connell JX, Huntsman D, van de Rijn M, Gilks CB, West RB. (2007)
Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides.
Am J Surg Pathol, 31 (6): 970-6. [PMID:17527089]
2. Fiocco U, Sfriso P, Lunardi F, Pagnin E, Oliviero F, Scagliori E, Cozzi L, Vezzù M, Molena B, Scanu A et al.. (2010)
Molecular pathways involved in synovial cell inflammation and tumoral proliferation in diffuse pigmented villonodular synovitis.
Autoimmun Rev, 9 (11): 780-4. [PMID:20620241]
3. Molena B, Sfriso P, Oliviero F, Pagnin E, Teramo A, Lunardi F, Stramare R, Scanu A, Nardacchione R, Rubaltelli L et al.. (2011)
Synovial colony-stimulating factor-1 mRNA expression in diffuse pigmented villonodular synovitis.
Clin Exp Rheumatol, 29 (3): 547-50. [PMID:21640049]
4. Smith CC, Zhang C, Lin KC, Lasater EA, Zhang Y, Massi E, Damon LE, Pendleton M, Bashir A, Sebra R et al.. (2015)
Characterizing and Overriding the Structural Mechanism of the Quizartinib-Resistant FLT3 "Gatekeeper" F691L Mutation with PLX3397.
Cancer Discov, 5 (6): 668-79. [PMID:25847190]
5. Tap WD, Wainberg ZA, Anthony SP, Ibrahim PN, Zhang C, Healey JH, Chmielowski B, Staddon AP, Cohn AL, Shapiro GI et al.. (2015)
Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor.
N Engl J Med, 373 (5): 428-37. [PMID:26222558]
6. Zhang J, Ibrahim PN, Artis DR, Bremer R, Wu G, Zhu H, Nespi M, Zhang C. (2011)
Compounds modulating c-fms and/or c-kit activity and uses therefor.
Patent number: US7893075 B2. Assignee: Plexxikon, Inc.. Priority date: 22/11/2006. Publication date: 22/02/2011.