FRAX486 HCL(1232030-35-1 free base)

SKU: orb1300417

Description

FRAX486 hydrochloride is a potent and selective p21-activated kinase (PAK) inhibitor, demonstrating IC50 values of 14 nM for PAK1, 33 nM for PAK2, 39 nM for PAK3, and 575 nM for PAK4. This small molecule is a valuable research tool for studying PAK signaling in cancer cell proliferation, neuronal morphology, and other cellular processes in both in vitro and in vivo models.

Research Area

Signal Transduction

Key Properties

• MW: 549.86
• Purity: 98.85% (May vary between batches)
• Formula: C₂₅H₂₄Cl₃FN₆O
• SMILES: FC1=CC(NC2=NC=C3C(N(C(C(C4=CC=C(C=C4Cl)Cl)=C3)=O)CC)=N2)=CC=C1N5CCNCC5.[H]Cl
• Target: PAK
• Solubility: DMSO:10.3 mg/mL (18.73 mM)

Bioactivity

• Target IC50:
  PAK4:575 nM|PAK1:14 nM|PAK2:33 nM|PAK3:39 nM
• In Vivo:
  FRAX486 crosses the blood-brain barrier and that therapeutically useful concentrations of FRAX486 are in the brain as early as 1 h and remain as long as 24 h after administration, with the maximum concentration in the target tissue at 8 h. Daily dosing results in steady-state levels of FRAX486 in the brain. FRAX486 specifically rescues the Fmr1 KO abnormality in which the spine phenotype is present in apical neurons and not simply decreasing spine density irrespective of genotype or existence of a phenotype. Also, FRAX486 reduces hyperactivity and stereotypical movements, both of which are phenotypes that characterize the mouse model of Fragile X syndrome.
• In Vitro:
  In WPMY-1 cells, FRAX486 induces concentration-dependent (1-10 μM) degeneration of actin filaments. This was paralleled by attenuation of proliferation rate, being observed from 1 to 10 μM FRAX486. Cytotoxicity of FRAX486 in WPMY-1 cells is time- and concentration-dependent. In WPMY-1 cells, effects of FRAX486 on actin organization, survival, and proliferation occurred already at concentrations of 1-5 μM. In these concentrations, full inhibition of PAK1-3 may be expected, while PAK4 may be inhibited only partially.
• Cell Research:
  Cells are grown in 96-well plates (20,000 cells/well) for 24 h, before FRAX486, IPA3, or DMSO are added in indicated concentrations (1, 5, 10 μM). Subsequently, cells are grown for different periods (24, 48, 72 h). Separate controls are performed for each period. At the end of this period, 10 μl of [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt (WST-8) from CCK-8 is added, and absorbance in each well is measured at 450 nm after incubation for 2 h at 37°C.

Storage & Handling

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

Alternative Names

PAK4, PAK3, PAK2, PAK1, FRAX486 HCL(1232030 35 1 free base), FRAX486 HCL(1232030351 free base), FRAX-486 HCL(1232030-35-1 free base), FRAX486 HCL(1232030-35-1 free base)

Compound Identifiers

PubChem CID

156598960