Pyrido[2,3-d]pyriMidin-7(8H)-one, 6-(2,4-dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]aMino]-
- CAS No.
- 1232030-35-1
- Chemical 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;CS-1943;FRAX 486; FRAX-486;6-(2,4-Dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]amino]pyrido[2,3-d]pyrimidin-7(8H)-one;6-(2,4-dichlorophenyl)-8-ethyl-2-((3-fluoro-4-(piperazin-1-yl)phenyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one;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
- CBNumber:
- CB82667850
- Molecular Formula:
- C25H23Cl2FN6O
- Molecular Weight:
- 513.39
- MDL Number:
- MFCD26793866
- MOL File:
- 1232030-35-1.mol
- MSDS File:
- SDS
Pyrido[2,3-d]pyriMidin-7(8H)-one, 6-(2,4-dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]aMino]- Properties
Boiling point | 689.9±65.0 °C(Predicted) |
---|---|
Density | 1.403±0.06 g/cm3(Predicted) |
storage temp. | -20°C |
solubility | insoluble in H2O; insoluble in DMSO; insoluble in ETOH |
form | powder |
pka | 8.75±0.10(Predicted) |
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]- price More Price(35)
Manufacturer | Product number | Product description | CAS number | Packaging | Price | Updated | Buy |
---|---|---|---|---|---|---|---|
Sigma-Aldrich | SML2270 | FRAX486 ≥98% (HPLC) | 1232030-35-1 | 5mg | $115 | 2024-03-01 | Buy |
Sigma-Aldrich | SML2270 | FRAX486 ≥98% (HPLC) | 1232030-35-1 | 25mg | $184.8 | 2024-03-01 | Buy |
Cayman Chemical | 24682 | FRAX486 | 1232030-35-1 | 5mg | $105 | 2024-03-01 | Buy |
Cayman Chemical | 24682 | FRAX486 | 1232030-35-1 | 25mg | $341 | 2024-03-01 | Buy |
Cayman Chemical | 24682 | FRAX486 | 1232030-35-1 | 1mg | $36 | 2024-03-01 | Buy |
Pyrido[2,3-d]pyriMidin-7(8H)-one, 6-(2,4-dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]aMino]- Chemical Properties,Uses,Production
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
storage
Store at -20°C
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
Raw materials
Preparation Products
Supplier | Tel | Country | ProdList | Advantage | |
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ATK CHEMICAL COMPANY LIMITED | +undefined-21-51877795 | ivan@atkchemical.com | China | 32836 | 60 |
Zhejiang J&C Biological Technology Co.,Limited | +1-2135480471 +1-2135480471 | sales@sarms4muscle.com | China | 10522 | 58 |
InvivoChem | +1-708-310-1919 +1-13798911105 | sales@invivochem.cn | United States | 6393 | 58 |
Hangzhou MolCore BioPharmatech Co.,Ltd. | +86-057181025280; +8617767106207 | sales@molcore.com | China | 49739 | 58 |
Nantong HI-FUTURE Biology Co., Ltd. | +undefined18051384581 | sales@chemhifuture.com | China | 3136 | 58 |
TargetMol Chemicals Inc. | +1-781-999-5354 | support@targetmol.com | United States | 19973 | 58 |
Shanghai Acmec Biochemical Technology Co., Ltd. | +undefined18621343501 | product@acmec-e.com | China | 33350 | 58 |
Aladdin Scientific | +1-+1(833)-552-7181 | sales@aladdinsci.com | United States | 57511 | 58 |
SHANGHAI KEAN TECHNOLOGY CO., LTD. | +8613817748580 | cooperation@kean-chem.com | China | 40068 | 58 |
Amadis Chemical Company Limited | 571-89925085 | sales@amadischem.com | China | 131980 | 58 |