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Details

Stereochemistry ACHIRAL
Molecular Formula C20H15ClF3N5
Molecular Weight 417.815
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PEXIDARTINIB

SMILES

FC(F)(F)C1=CC=C(CNC2=CC=C(CC3=CNC4=C3C=C(Cl)C=N4)C=N2)C=N1

InChI

InChIKey=JGWRKYUXBBNENE-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Description

Pexidartinib (PLX3397) is a small-molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Pexidartinib binds to and inhibits phosphorylation of stem cell factor receptor (KIT), colony-stimulating factor-1 receptor (CSF1R) and FMS-like tyrosine kinase 3 (FLT3), which may result in the inhibition of tumor cell proliferation and down-modulation of macrophages, osteoclasts and mast cells involved in the osteolytic metastatic disease. FDA has granted Breakthrough Therapy Designation to pexidartinib (PLX3397) for the treatment of tenosynovial giant cell tumor (TGCT) where surgical removal of the tumor would be associated with potentially worsening functional limitation or severe morbidity. In addition to Breakthrough Therapy Designation, pexidartinib (PLX3397) has been granted Orphan Drug Designation by FDA for the treatment of pigmented villonodular synovitis (PVNS) and giant cell tumor of the tendon sheath (GCT-TS). It also has received Orphan Designation from the European Commission for the treatment of TGCT.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides.
2007 Jun
Molecular pathways involved in synovial cell inflammation and tumoral proliferation in diffuse pigmented villonodular synovitis.
2010 Sep
Synovial colony-stimulating factor-1 mRNA expression in diffuse pigmented villonodular synovitis.
2011 May-Jun
Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor.
2015 Jul 30
Colony-Stimulating Factor 1 Receptor Blockade Inhibits Tumor Growth by Altering the Polarization of Tumor-Associated Macrophages in Hepatocellular Carcinoma.
2017 Aug
Patents

Sample Use Guides

In Vivo Use Guide
1000 mg per day for 2 weeks (dose split over morning and evening), then 800 mg per day for 22 weeks (dose split over morning and evening).
Route of Administration: Oral
In Vitro Use Guide
In vitro, a population doubling assay showed that the IC50 of pexidartinib (PLX3397) for CSF1-induced bone marrow–derived macrophages (M(CSF1)) was 22 nM. Marked suppression of CSF-1R phosphorylation in M(CSF1) cells could be achieved with PLX3397. In contrast, the same doses of PLX3397 showed no antiproliferation effect on Hepa1-6, MHCC97-H, HCCLM3, HepG2, HUVEC, T cells, fibroblasts cells, and CSF2-induced bone marrow–derived macrophages.
Name Type Language
PEXIDARTINIB
INN   WHO-DD  
INN  
Official Name English
PEXIDARTINIB [INN]
Common Name English
PLX3397
Code English
PLX-3397
Code English
PEXIDARTINIB [USAN]
Common Name English
PEXIDARTINIB [WHO-DD]
Common Name English
CML-261
Code English
5-((5-CHLORO-1H-PYRROLO(2,3-B)PYRIDIN-3-YL)METHYL)-N-((6-(TRIFLUOROMETHYL)PYRIDIN-3-YL)METHYL)PYRIDIN-2-AMINE
Systematic Name English
3-PYRIDINEMETHANAMINE, N-(5-((5-CHLORO-1H-PYRROLO(2,3-B)PYRIDIN-3-YL)METHYL)-2-PYRIDINYL)-6-(TRIFLUOROMETHYL)-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 19:44:26 UTC 2019 , Edited by admin on Mon Oct 21 19:44:26 UTC 2019
NCI_THESAURUS C1967
Created by admin on Mon Oct 21 19:44:26 UTC 2019 , Edited by admin on Mon Oct 21 19:44:26 UTC 2019
Code System Code Type Description
ChEMBL
CHEMBL3545158
Created by admin on Mon Oct 21 19:44:26 UTC 2019 , Edited by admin on Mon Oct 21 19:44:26 UTC 2019
PRIMARY
CAS
1029044-16-3
Created by admin on Mon Oct 21 19:44:26 UTC 2019 , Edited by admin on Mon Oct 21 19:44:26 UTC 2019
PRIMARY
INN
10056
Created by admin on Mon Oct 21 19:44:26 UTC 2019 , Edited by admin on Mon Oct 21 19:44:26 UTC 2019
PRIMARY
PUBCHEM
25151352
Created by admin on Mon Oct 21 19:44:26 UTC 2019 , Edited by admin on Mon Oct 21 19:44:26 UTC 2019
PRIMARY
NCI_THESAURUS
C88303
Created by admin on Mon Oct 21 19:44:26 UTC 2019 , Edited by admin on Mon Oct 21 19:44:26 UTC 2019
PRIMARY
CAS
1447274-99-8
Created by admin on Mon Oct 21 19:44:26 UTC 2019 , Edited by admin on Mon Oct 21 19:44:26 UTC 2019
NO STRUCTURE GIVEN