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| Pyrido[2,3-d]pyriMidin-7(8H)-one, 6-(2,4-dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]aMino]- Basic information |
| Product Name: | Pyrido[2,3-d]pyriMidin-7(8H)-one, 6-(2,4-dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]aMino]- | | Synonyms: | FRAX486;6-(2,4-Dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]amino]pyrido[2,3-d]pyrimidin-7(8H)-one;CS-1943;Pyrido[2,3-d]pyriMidin-7(8H)-one, 6-(2,4-dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]aMino]-;6-(2,4-dichlorophenyl)-8-ethyl-2-{[3-fluoro-4-(1-piperazinyl)phen Yl]amino}pyrido[2,3-d]pyrimidin-7(8h)-one FRAX597;6-(2,4-dichlorophenyl)-8-ethyl-2-((3-fluoro-4-(piperazin-1-yl)phenyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one;FRAX 486; FRAX-486 | | CAS: | 1232030-35-1 | | MF: | C25H23Cl2FN6O | | MW: | 513.39 | | EINECS: | | Product Categories: | | Mol File: | 1232030-35-1.mol |
| Pyrido[2,3-d]pyriMidin-7(8H)-one, 6-(2,4-dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]aMino]- Chemical Properties |
| storage temp. | -20°C | | solubility | insoluble in H2O; insoluble in DMSO; insoluble in ETOH | | form | powder | | color | white to beige |
| Pyrido[2,3-d]pyriMidin-7(8H)-one, 6-(2,4-dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]aMino]- Usage And Synthesis |
| Description | FRAX486 is an inhibitor of group I p21-activated kinases (PAKs; IC50s = 8.25, 39.5, and 55.3 nM for PAK1, PAK2, and PAK3, respectively). It is selective for group I PAKs over PAK4, a group II PAK (IC50 = 779 nM). FRAX486 (20 mg/kg) reverses decreases in the mean density of apical dendritic spines in the temporal cortex in the Fmr1-/- mouse model of fragile X syndrome. It completely abolishes audiogenic seizures, hyperactivity, and stereotypical movements in Fmr1-/- mice when administered at a dose of 30 mg/kg. FRAX486 prevents adolescent cortical dendritic spine loss and rescues prepulse inhibition deficits in a Disc1 knockdown mouse model of schizophrenia. | | Uses | FRAX 486 is a small-molecule PAK inhibitor. This compound has neuroprotective properties. | | Biochem/physiol Actions | FRAX486 is a potent, group I-selective p21-activated kinase (PAK) inhibitor (PAK1/2/3 IC50 = 8.25/39.5/55.3 nM; group II PAK4 IC50 = 779 nM). FRAX486 effectively inhibits PAK-mediated PKD1 Ser203 phosphorylation and PAK1/2 Ser144/141 autophosphorylation upon angiotensin II (ANGII) stimulation of rat IEC-18 cells (IC50 ～0.5 μM) and exhibits in vivo efficacy in rescuing the autism-like phenotypes among Fmr1 knockout fragile syndrome (FXS) mice (20 mg/kg s.c.) as well as in ameliorating schizophrenia-associated dendritic spine deterioration among Disc1 knockdown mice (10 μg/g or 10 mg/kg i.p.) with good pharmacokinetic properties and blood–brain barrier (BBB) permeability. | | in vitro | previous study showed in wpmy-1 cells, frax486 could dose-dependently induce the degeneration of actin filaments, which was accompanied by proliferation rate attenuation. moreover, the frax486 cytotoxicity in wpmy-1 cells was found to be both time- and concentration-dependent. in addition, the effects of frax486 on actin organization, survival, and proliferation were observed at 1-5 μm in wpmy-1 cells, and complete inhibition of pak1-3 might be expected, whereas pak4 might be inhibited only partially at these concentrations [1]. | | in vivo | animal study found that frax486 was able to cross the blood-brain barrier (bbb) and the brain therapeutical frax486 concentrations were detected as early as 1 h and remained as long as 24 h, with the maximum concentration (cmax) at 8 h. moreover, frax486 could reduce hyperactivity and stereotypical movements, both of which were phenotypes characterizing the fragile x syndrome mouse model [2]. | | IC 50 | 14, 33, 39 and 575 nm for pak1, pak2, pak3 and pak4 respectively | | references | [1] wang y,et al. p21-activated kinase inhibitors frax486 and ipa3: inhibition of prostate stromal cell growth and effects on smooth muscle contraction in the human prostate. plos one. 2016 apr 12;11(4):e0153312. [2] dolan bm,duron sg,campbell da,vollrath b,shankaranarayana rao bs,ko hy,lin gg,govindarajan a,choi sy,tonegawa s. rescue of fragile x syndrome phenotypes in fmr1 ko mice by the small-molecule pak inhibitor frax486. proc natl acad sci u s a. 2013 apr 2;110(14):5671-6. |
| Pyrido[2,3-d]pyriMidin-7(8H)-one, 6-(2,4-dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]aMino]- Preparation Products And Raw materials |
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