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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2D Structure
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Physico-chemical Properties
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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
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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)
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.