Pexidartinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种口服活性、BBB 渗透性、CSF-1R、Kit 和 Flt3 的强效多靶点 RTK 抑制剂，IC50 分别为 20 nM、10 nM 和 160 nM。

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.

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.

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.

PLX-3397 | PLX3397

Tyrosine Kinase

CSF1R

CSF-1R|FLT3|Kit

Cancer

Skin Cancer

1029044-16-3

417.8148

C20H15ClF3N5

>98% (HPLC)

DMSO: ≥ 30 mg/mL

FC(F)(F)C1=NC=C(CNC2=NC=C(CC3=CNC4=NC=C(Cl)C=C34)C=C2)C=C1

3-Pyridinemethanamine, N-[5-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2-pyridinyl]-6-(trifluoromethyl)-

(-20℃)

With Ice Pack

≥ 2 years