Pexidartinib

SKU: orb1227118

Description

An oral-active, BBB-penatrant, potent mutil-targeted RTK inhibitor of CSF-1R, Kit, and Flt3 with IC50 of 20 nM, 10 nM and 160 nM, respectively; inhibits the CSF1-dependent proliferation with IC50 of 0.44 uM, 0.22 uMand 0.1 uM in M-NFS-60, Bac1.2F5 and M-07e cells, respectively; significantly inhibits PTX-induced tumor infiltration in mice.Skin Cancer Phase 2 Clinical(In Vitro):Pexidartinib (PLX-3397) 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 (PLX3397; 0.25, 1 mg/kg, twice daily for 8 days) inhibits the proliferation of microglia and BrdU-positive cells in neonatal mice.Pexidartinib (1 mg/kg, twice daily for 8 day) shows no obvious effect on the cleaved caspase-3-positive cells in mice.Pexidartinib (50 mg/kg; p.o.; every second day for 3 weeks) reduces tissue macrophage levels without affecting glucose homeostasis in mice.

Key Properties

• CAS Number: 1029044-16-3
• MW: 417.8148
• Purity: >98% (HPLC)
• Formula: C₂₀H₁₅ClF₃N₅
• SMILES: FC(F)(F)C1=NC=C(CNC2=NC=C(CC3=CNC4=NC=C(Cl)C=C34)C=C2)C=C1
• Target: CSF1R
• Solubility: DMSO: ≥ 30 mg/mL

Bioactivity

• In Vivo:
  Pexidartinib (PLX3397; 0.25, 1 mg/kg, twice daily for 8 days) inhibits the proliferation of microglia and BrdU-positive cells in neonatal mice. Pexidartinib (1 mg/kg, twice daily for 8 day) shows no obvious effect on the cleaved caspase-3-positive cells in mice. Pexidartinib (50 mg/kg; p.o. ; every second day for 3 weeks) reduces tissue macrophage levels without affecting glucose homeostasis in mice. Animal model: Neonatal mice. Dosage: 0.25, 1 mg/kg. Administration: i.p. twice daily for 8 days. Result: Decreased the number of microglia and BrdU-positive proliferative cells, but did not change the cleaved caspase-3-positive cells. Animal model: 10-week old litter mate C57BL/6 mice (chow and high-fat diet fed mice). Dosage: 50 mg/kg. Administration: p.o. ; every second day for 3 weeks. Result: Substantially reduced macrophage numbers in adipose tissue of both chow and high-fat diet fed mice without affecting total myeloid cell levels.
• In Vitro:
  Pexidartinib (PLX-3397) 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

PLX-3397 | PLX3397

Quick Database Links

Gene Symbol

CSF1R