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)
No information available.
Summary of Clinical Use Click here for help
The US FDA granted pexidartinib orphan drug designation for the proliferative disorder tenosynovial giant cell tumour (TGCT; a.k.a. pigmented villonodular synovitis or PVNS) in 2014. Following Priority Review, the FDA approved pexidartinib in August 2019, as a treament for symptomatic TGCT in adult patients with severe morbidity or functional limitations, and whose symptoms are not improved by surgery.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
CSF1R is a primary driver in PVNS [1-3], and expression is elevated in most tumours of this type [5]. PLX3397 stabilises the kinase in an autoinhibited conformation, the clinical outcome of which is partial response or stable disease in patients with PVNS [5].