| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
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| Other Sizes |
Purity: ≥98%
| Targets |
PAK1 (IC50 = 14 nM); PAK2 (IC50 = 33 nM); PAK3 (IC50 = 39 nM); PAK4 (IC50 = 575 nM)
FRAX486 targets p21-activated kinases (PAKs), specifically PAK1, PAK2, PAK3, and to a lesser extent PAK4. PAKs are serine/threonine kinases that play roles in cell proliferation, migration, and survival. By inhibiting PAK1, PAK2, and PAK3 with high potency (IC50 values of 14, 33, and 39 nM, respectively), FRAX486 blocks downstream signaling pathways. |
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| ln Vitro |
FRAX486 causes concentration-dependent (1–10 μM) actin filament degeneration in WPMY-1 cells. Attenuation of the proliferation rate was also observed between 1 and 10 μM FRAX486. In WPMY-1 cells, FRAX486's cytotoxicity is concentration- and time-dependent. FRAX486 had effects on actin organization, survival, and proliferation in WPMY-1 cells as early as 1–5 μM. While only partial inhibition of PAK4 may occur at these concentrations, complete inhibition of PAK1-3 may be anticipated[2].
In vitro, FRAX486 is a potent PAK inhibitor, with IC50 values of 14, 33, 39, and 575 nM for PAK1, PAK2, PAK3, and PAK4, respectively. Its potent and selective inhibition of Group I PAKs has been characterized in kinase assays. Its ability to penetrate cells has been demonstrated. |
| ln Vivo |
FRAX486 is able to penetrate the blood-brain barrier. It can reach the brain as early as 1 hour after administration and stay there for up to 24 hours.Its maximum concentration in the target tissue is reached after 8 hours. FRAX486 levels in the brain stabilize after daily dosing. Instead of just decreasing spine density regardless of genotype or phenotypic presence, FRAX486 specifically rescues the Fmr1 KO abnormality, in which the spine phenotype is present in apical neurons. Moreover, FRAX486 lessens stereotypical movements and hyperactivity, two traits that define the mouse model of fragile X syndrome[3].
In vivo, FRAX486 is able to penetrate the blood-brain barrier. It reaches the brain as early as 1 hour after administration and stays there for up to 24 hours, with a maximum concentration in the target tissue reached after 8 hours. This makes it a valuable tool for studying PAK function in the central nervous system. |
| Enzyme Assay |
In vitro kinase assays for FRAX486 measure its inhibition of PAK1, PAK2, PAK3, and PAK4 activity. The compound is incubated with each kinase and a peptide substrate in the presence of ATP. The IC50 values are determined from dose-response curves.
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| Cell Assay |
WPMY-1 cells are plated on a coverslip with 16 wells and a density of 50,000/well. Cells are treated with FRAX486 (1, 5, 10 μM), IPA3 (1, 5, 10 μM), or DMSO after a 24-hour period. A further twenty-four hours later, the medium is swapped out for a 10-mM 5-ethynyl-2'-deoxyuridine (EdU) solution in an FCS-free medium that contains solvent or inhibitors. Cells were fixed with 3.7% formaldehyde 20 hours later. Utilizing the "EdU-Click 555" cell proliferation assay, EdU incorporation is studied. The assay measures the amount of EdU incorporated into DNA by using fluorescing 5-carboxytetramethylrhodamine (5-TAMRA) to detect the incorporation. Every nucleus is counterstained using DAPI. Fluorescence microscopy is used to examine cells (emission: 479 nm; excitation: 546 nm).
In vitro cell-based assays for FRAX486 involve treating cells with the compound and measuring PAK phosphorylation levels. Its effects on cell proliferation, migration, and survival are assessed in various cell lines. Its ability to penetrate cells is confirmed in these assays. |
| Animal Protocol |
Mice: There are male C57BL/6 mice that are fasted. When it comes to FRAX486, the intravenous (IV) dose is 3 mg/kg with a 1 mg/mL solution in 20% (wt/vol) 2-hydroxypropyl-β-cyclodextrin in water, and the oral (PO) dose is 30 mg/kg with a 3 mg/mL solution in water. In the in vivo trial, FRAX486 is injected intraperitoneally [10 μg/BW (g)] once daily between P35 and P60, resulting in brain concentrations greater than 175 nM.
In vivo animal experiments for FRAX486 have been conducted to assess its brain penetration. Animals are administered the compound, and its concentration in the brain is measured at various time points. Its effects on PAK signaling in the brain are also assessed. |
| ADME/Pharmacokinetics |
FRAX486 has a molecular weight of 513.39 and a molecular formula of C25H23Cl2FN6O. It has a density of 1.4±0.1 g/cm3 and a boiling point of 689.9±65.0 °C. Its purity is >98%. It is typically stored at -20°C.
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| Toxicity/Toxicokinetics |
FRAX486 is for research use only and is not intended for human use. Its safety profile is being evaluated in preclinical studies. As a potent PAK inhibitor, its toxicity is related to its mechanism of action. Standard safety precautions should be taken when handling.
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| References | |
| Additional Infomation |
FRAX486 is a potent PAK inhibitor with IC50 values of 14, 33, 39, and 575 nM for PAK1, PAK2, PAK3, and PAK4, respectively. It is able to penetrate the blood-brain barrier. It reaches the brain rapidly and stays there for up to 24 hours. It is a research compound for studying PAK function in the CNS.
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| Molecular Formula |
C25H23CL2FN6O
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|---|---|
| Molecular Weight |
513.4
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| Exact Mass |
512.129
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| Elemental Analysis |
C, 58.49; H, 4.52; Cl, 13.81; F, 3.70; N, 16.37; O, 3.12
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| CAS # |
1232030-35-1
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| Related CAS # |
1232030-35-1
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| PubChem CID |
68060125
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.893
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
35
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| Complexity |
783
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1=CC(NC2=NC=C3C(N(CC)C(C(C4=CC=C(Cl)C=C4Cl)=C3)=O)=N2)=CC=C1N5CCNCC5
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| InChi Key |
DHKFOIHIUYFSOF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H23Cl2FN6O/c1-2-34-23-15(11-19(24(34)35)18-5-3-16(26)12-20(18)27)14-30-25(32-23)31-17-4-6-22(21(28)13-17)33-9-7-29-8-10-33/h3-6,11-14,29H,2,7-10H2,1H3,(H,30,31,32)
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| Chemical Name |
6-(2,4-dichlorophenyl)-8-ethyl-2-(3-fluoro-4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one
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| Synonyms |
FRAX486; FRAX 486; FRAX-486
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 21.2~30 mg/mL (41.3~58.4 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9478 mL | 9.7390 mL | 19.4780 mL | |
| 5 mM | 0.3896 mL | 1.9478 mL | 3.8956 mL | |
| 10 mM | 0.1948 mL | 0.9739 mL | 1.9478 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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