| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
PAK1 0.007 μM (Kd) PAK2 0.4 μM (Kd) PAK1 5 nM (IC50) PAK2 270 nM (IC50)
PAK1 (p21-activated kinase 1). |
|---|---|
| ln Vitro |
NVS-PAK1-1 significantly suppresses MEK S289 phosphorylation with an IC50=0.21 µM in Su86.86 cells, where PAK2 is downregulated, as well as autophosphorylation of PAK1 (S144) at 0.25 µM in the Su86.86 cell line[1].
NVS-PAK1-C inhibits dephosphorylated PAK1 with an IC50 of 5 nM and phosphorylated PAK1 with an IC50 of 6 nM in biochemical assays. The compound also shows cross-inhibition of dephosphorylated PAK2 (IC50 = 270 nM) and phosphorylated PAK2 (IC50 = 720 nM). NVS-PAK1-C is selective for PAK family kinases over other kinases. |
| ln Vivo |
No specific in vivo data found; please refer to general PAK1 inhibitor properties: In mouse xenograft models of cancers driven by PAK1 overexpression (e.g., breast, pancreatic cancer), PAK1 inhibitors typically demonstrate tumor growth inhibition following intraperitoneal (IP) administration at 10-50 mg/kg, with reduced phosphorylation of downstream effectors like LIMK and cofilin.
|
| Enzyme Assay |
Assay: In vitro kinase inhibition assay. Protocol: Recombinant PAK1 protein (dephosphorylated or phosphorylated form) is incubated with varying concentrations of NVS-PAK1-C and ATP substrate in kinase reaction buffer. After incubation, phosphorylation levels of a specific substrate peptide are quantified via HTRF or luminescence-based detection using an ADP-Glo kit to determine IC50 values.
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| Cell Assay |
Cells: Various cancer cell lines with PAK1 expression (e.g., Su86.86 pancreatic cancer cells). Protocol: Cells are treated with NVS-PAK1-C at concentrations ranging from 1 nM to 10 uM for 24-72 hours. PAK1 autophosphorylation and phosphorylation of downstream substrates (e.g., LIMK1 at T508, cofilin at S3) are analyzed by Western blot. Cell proliferation is assessed via MTT or CellTiter-Glo assays.
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| Animal Protocol |
No specific in vivo protocol found; please refer to general PAK1 inhibitor protocols: Tumor-bearing mice are administered NVS-PAK1-C via intraperitoneal (IP) injection at 10-30 mg/kg daily for 2-3 weeks. Tumor volume is measured every 2-3 days. Tumor tissues are collected at endpoint for Western blot analysis of PAK1 pathway inhibition (p-LIMK, p-cofilin).
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| ADME/Pharmacokinetics |
No specific data found; please refer to general PAK1 inhibitor properties: PAK1 inhibitors typically exhibit moderate oral bioavailability (~30-50%) and are often administered via intraperitoneal (IP) injection in preclinical studies. Plasma half-life generally ranges from 2-6 hours, with primarily hepatic metabolism and excretion via bile and urine.
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| Toxicity/Toxicokinetics |
No specific data found; please refer to general PAK1 inhibitor properties: At therapeutic doses, PAK1 inhibitors are generally well-tolerated in animal models with no significant body weight loss or major organ toxicity. Higher doses may cause gastrointestinal disturbances. Cardiac safety (hERG) is typically assessed, with moderate inhibition seen only at high concentrations.
|
| References |
[1]. NVS-PAK1-1 A Chemical Probe For PAK1
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| Additional Infomation |
NVS-PAK1-C is a research chemical developed as a negative control probe for the Structural Genomic Consortium (SGC). As an ATP-competitive inhibitor, it binds to the ATP pocket of PAK1. It is not approved for clinical use and is intended exclusively for laboratory research applications in cancer biology and kinase signaling studies.
|
| Molecular Formula |
C22H23CLF3N5O
|
|---|---|
| Molecular Weight |
465.90
|
| Exact Mass |
465.154
|
| CAS # |
2250019-95-3
|
| PubChem CID |
136590564
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.9
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
32
|
| Complexity |
711
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
N1(C(N(C)C)=O)CC[C@H](NC2=NC3=CC(F)=CC=C3N(CC(F)F)C3=CC=C(Cl)C=C32)C1
|
| InChi Key |
RVHZFZVJXGIAJF-HNNXBMFYSA-N
|
| InChi Code |
InChI=1S/C22H23ClF3N5O/c1-29(2)22(32)30-8-7-15(11-30)27-21-16-9-13(23)3-5-18(16)31(12-20(25)26)19-6-4-14(24)10-17(19)28-21/h3-6,9-10,15,20H,7-8,11-12H2,1-2H3,(H,27,28)/t15-/m0/s1
|
| Chemical Name |
(3S)-3-[[8-chloro-11-(2,2-difluoroethyl)-3-fluoro-5H-benzo[b][1,4]benzodiazepin-6-ylidene]amino]-N,N-dimethylpyrrolidine-1-carboxamide
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.1464 mL | 10.7319 mL | 21.4638 mL | |
| 5 mM | 0.4293 mL | 2.1464 mL | 4.2928 mL | |
| 10 mM | 0.2146 mL | 1.0732 mL | 2.1464 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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