Pexidartinib 是具有口服活性的选择性ATP-竞争性的集落刺激因子 1 和c-Kit抑制剂，IC50值分别为 20 和 10 nM。它可诱导细胞凋亡，具有抗肿瘤活性。

Pexidartinib is a capsule formulation containing a small-molecule receptor tyrosine kinase (RTK) inhibitor of KIT, CSF1R and FLT3 with potential antineoplastic activity.

In M-NFS-60, Bac1.2F5 and M-07e cells, Pexidartinib inhibits the CSF1-dependent proliferation with IC50 of 0.44 μM, 0.22 μMand 0.1 μM, respectively. [1]

In MMTV-PyMT mice, Pexidartinib (40 mg/kg, p.o.) significantly inhibits both steady-state and PTX-induced tumor infiltration by CD45+CD11b+Ly6C?Ly6 g?F4/80+. Pexidartinib/PTX therapy also results in a significant reduction in CD31+ vessel density within mammary tumors, paralleling induction of apoptosis and necrosis. [1] In C57 mice bearing GL261 tumors, Pexidartinib (p.o.) inhibits glioblastoma invasion. [2] In cmo mice, PLX3397 significantly attenuates autoinflammatory disease by decreasing the erosive bone lesions in tails and paws and the levels of circulating MIP-1α. [3] In mice bearing B16F10 melanomas, Pexidartinib (45 mg/kg, p.o.) enhances CD8-mediated immunotherapy of melanoma. [4]

Competitive binding fluorescent polarization assay: Recombinant Hsp90β, TAMRA-radicicol, or various concentrations of NVP-BEP800 is added in assay buffer (50 mM TRIS pH 7.4, 5 mM MgCl2, 150 mM KCl, and 0.1% CHAPS), mixed, and incubated at room temperature for 30 to 45 minutes prior to reading. The 2D-FIDA-based HTS assay based on confocal technologies monitors the decreased fluorescence polarization on displacement of the high affinity ligand TAMRA-radicicol from Hsp90β by NVP-BEP800. The concentration of NVP-BEP800 which inhibits Hsp90β by 50% is determined from the competition curve.

1029044-16-3

C20H15ClF3N5

417.82

PLX-3397

DMSO:77 mg/mL (184.3 mM)
Ethanol:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years