FRAX486 is a p21-activated kinase (PAK) inhibitor with IC50s of 14, 33 and 39 nM for PAK1, PAK2 and PAK3, respectively. in vitro kinase assays using pure enzymes reveal IC50s for FRAX486 between 10-100 nM for PAK1-3, while the IC50 of 779 nM for PAK4 is just below the micromolar range. In WPMY-1 cells, FRAX486 (24 h) induces concentration-dependent (1-10 μM) degeneration of actin filaments. FRAX486 (1-10 μM, 24 h) causes concentration-dependent degeneration of actin filaments. Actin filaments in solvent-treated control cells are arranged to bundles, forming long and thin protrusions, with elongations from adjacent cells overlapping each other. FRAX486 in concentrations of 1 μM causes partial loss of actin organization, including regressing degree of actin polymerization and degeneration of protrusions. FRAX486 in concentrations of 5 or 10 μM causes complete breakdown of filament organization, resulting in a rounded cell shape without protrusions[1].
体内研究
FRAX486 displays the highest penetrance of blood–brain barrier in DISC1-knockdown C57BL/6 mice. Daily administration of FRAX486, but not that of vehicle, between P35 and P60 blocks the exacerbated spine loss during adolescence. In addition to the significant blockade of spine elimination, a trend of enhanced spine generation is observed by treatment with FRAX486[2].
体外研究
FRAX486 is a p21-activated kinase (PAK) inhibitor with IC50s of 14, 33 and 39 nM for PAK1, PAK2 and PAK3, respectively. in vitro kinase assays using pure enzymes reveal IC50s for FRAX486 between 10-100 nM for PAK1-3, while the IC50 of 779 nM for PAK4 is just below the micromolar range. In WPMY-1 cells, FRAX486 (24 h) induces concentration-dependent (1-10 μM) degeneration of actin filaments. FRAX486 (1-10 μM, 24 h) causes concentration-dependent degeneration of actin filaments. Actin filaments in solvent-treated control cells are arranged to bundles, forming long and thin protrusions, with elongations from adjacent cells overlapping each other. FRAX486 in concentrations of 1 μM causes partial loss of actin organization, including regressing degree of actin polymerization and degeneration of protrusions. FRAX486 in concentrations of 5 or 10 μM causes complete breakdown of filament organization, resulting in a rounded cell shape without protrusions[1].
FRAX486 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MV4-11 cells
1 µM
72 h
FRAX-486 blocked proliferation and induced apoptosis in MV4-11 cells
Cell Commun Signal. 2025 Mar 13;23(1):135.
P31/Fuj cells
10 µM
72 h
FRAX-486 blocked proliferation and induced apoptosis in P31/Fuj cells
Cell Commun Signal. 2025 Mar 13;23(1):135.
E0771
2 μM
24 h
FRAX486 significantly inhibited migration and invasion of TNBC cells by blocking autophagic degradation of E-cadherin.
Br J Cancer. 2024 Feb;130(3):394-405.
MDA-MB-231
2 μM
24 h
FRAX486 significantly inhibited migration and invasion of TNBC cells by blocking autophagic degradation of E-cadherin.
Br J Cancer. 2024 Feb;130(3):394-405.
fibroblasts
50 nM
1 hour
To investigate the effect of FRAX486 on reversing the cellular phenotype caused by PAK1 mutations, results showed FRAX486 completely reversed the cellular phenotype
Am J Hum Genet. 2018 Oct 4;103(4):579-591.
primary hippocampal neurons
100 nM
48 h
To evaluate the rescue effect of FRAX486 on CDKL5 deficiency-related neuronal maturation and synaptic defects. Results showed that FRAX486 completely rescued the abnormal neuronal maturation and the number of PSD95-positive puncta in Cdkl5-KO mouse neurons.
CNS Neurosci Ther. 2022 Nov;28(11):1718-1732.
Trichophyton rubrum mycelia
3.1 µM
10 days
To evaluate the inhibitory effect of FRAX486 on mycelial growth, results showed that FRAX486 significantly inhibited mycelial growth
Microbiol Spectr. 2023 Dec 12;11(6):e0292323.
Trichophyton rubrum spores
50 µM
21 h
To evaluate the inhibitory effect of FRAX486 on spore germination, results showed that FRAX486 significantly inhibited spore germination
Microbiol Spectr. 2023 Dec 12;11(6):e0292323.
FRAX486 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Syrian hamsters
SARS-CoV-2 infection model
Oral
30 mg/kg
Once daily for a total of four doses
To evaluate the in vivo anti-SARS-CoV-2 activity of FRAX-486
Signal Transduct Target Ther. 2023 Oct 9;8(1):385
Mice
Fmr1 KO mice
Subcutaneous injection
20 mg/kg
Single dose or daily for 5 days
FRAX486 reversed the increased dendritic spine density, seizures, hyperactivity, and repetitive behaviors in Fmr1 KO mice.
Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5671-6
Balb/c nude mice
TNBC lung metastasis model
Gavage
20 mg/kg
5 days per week for 7 weeks
FRAX486 significantly reduced the number of lung metastatic nodules of TNBC cells, inhibiting autophagy-dependent metastasis.
Br J Cancer. 2024 Feb;130(3):394-405.
NSG mice
FLT3D835H PDX-ALL model
Subcutaneous injection of FRAX486 and oral midostaurin
The combination of sotorasib with FRAX597 led to noticeable tumour regression.
Br J Cancer. 2023 Jan;128(1):148-159
Mice
Female mouse model of CDKL5 deficiency disorder
Subcutaneous injection
20 mg/kg
Once daily for 5 consecutive days
To assess the therapeutic effects of FRAX486 on behavioral abnormalities and metabolic defects in Cdkl5-Het mice. Results showed that FRAX486 improved general health status, hyperactive behavior, and fear learning deficits, and restored the levels of reactive oxidizing species in the blood and fasting-induced hypoglycemia.
CNS Neurosci Ther. 2022 Nov;28(11):1718-1732.
Silkworm
Silkworm infection model
Injection
0.5 mM
Single injection, survival monitored
To evaluate the therapeutic effect of FRAX486 in the silkworm infection model, results showed that FRAX486 significantly improved survival rates
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