Pexidartinib HCl

Pexidartinib, also know as PLX-3397, is a CSF1R inhibitor with IC50 of 20 nM in development by Plexxikon for the treatment of tenosynovial giant cell tumors. It is in a phase 3 clinical trial for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS).

Product information

CAS Number: 2040295-03-0

Molecular Weight: 454.28

Formula: C20H16Cl2F3N5

Synonym:

PLX-3397

CML-261

FP-113

Pexidartinib hydrochloride

Turalio

Chemical Name:  5-((5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyridin-2-amine hydrochloride

Smiles: Cl.FC(F)(F)C1=CC=C(CNC2=CC=C(CC3=CNC4=NC=C(Cl)C=C34)C=N2)C=N1

InChiKey: CJLUYLRKLUYCEK-UHFFFAOYSA-N

InChi: InChI=1S/C20H15ClF3N5.ClH/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);1H

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Pexidartinib hydrochloride (PLX-3397 hydrochloride) is a potent, selective and ATP-competitive CSF1R (cFMS) and c-Kit inhibitor, shows 10- to 100-fold selectivity for c-Kit and CSF1R over other related kinases, such as FLT3, KDR (VEGFR2), LCK, FLT1 (VEGFR1) and NTRK3 (TRKC), with IC50s of 160, 350, 860, 880, and 890 nM, respectively.

In Vivo:

Pexidartinib hydrochloride (0.25, 1 mg/kg, i.p., twice daily for 8 days) inhibits the proliferation of microglia and BrdU-positive cells in neonatal mice. Pexidartinib hydrochloride (1 mg/kg, twice daily for 8 day) shows no obvious effect on the cleaved caspase-3-positive cells in mice. Pexidartinib hydrochloride (50 mg/kg; p.o.; every second day for 3 weeks) reduces tissue macrophage levels without affecting glucose homeostasis in mice.

References:

1. Lamb YN. Pexidartinib: First Approval. Drugs. 2019 Nov;79(16):1805-1812. doi: 10.1007/s40265-019-01210-0. Review. PubMed PMID: 31602563.
2. Mason C, Kossatz S, Carter L, Pirovano G, Brand C, Guru N, Pérez-Medina C, Lewis JS, Mulder W, Reiner T. A (89)Zr-HDL PET tracer monitors response to a CSF1R inhibitor. J Nucl Med. 2019 Aug 16. pii: jnumed.119.230466. doi: 10.2967/jnumed.119.230466. [Epub ahead of print] PubMed PMID: 31420495.
3. Piawah S, Hyland C, Umetsu SE, Esserman LJ, Rugo HS, Chien AJ. A case report of vanishing bile duct syndrome after exposure to pexidartinib (PLX3397) and paclitaxel. NPJ Breast Cancer. 2019 Jun 14;5:17. doi: 10.1038/s41523-019-0112-z. eCollection 2019. PubMed PMID: 31240240; PubMed Central PMCID: PMC6570645.

Products are for research use only. Not for human use.