| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| 10mg | |||
| 50mg | |||
| Other Sizes |
| Targets |
CDK2 and CDK5 (Cyclin-dependent kinases).
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|---|---|
| ln Vitro |
In a panel of colorectal cancer (CRC) cell lines, the CDK5 inhibitor 20-223 (10 nM-10 μM; 72 h) efficiently reduces cell proliferation [1]. Three CRC cell lines were treated at reduced doses with CDK5 inhibitor 20-223 (0.3125 – 20,000 μM; 6 h) to induce pRB (S807/811) and pFAK (S732) levels [1].
In vitro, 20-223 inhibits CDK5 and CDK2 kinase activity, reduces phosphorylation of downstream substrates (pRB and pFAK), and blocks CRC cell migration. It shows antiproliferative activity across multiple CRC cell lines with mean IC50 of 362 nM. |
| ln Vivo |
In human colorectal cancer xenograft tumors in nude mice, the CDK5 inhibitor 20-223 (8 mg/kg; subcutaneous injection; 14 injections) demonstrated tumor anti-tumor efficacy [1].
In vivo, 20-223 (8 mg/kg; subcutaneously; 14 injections) significantly reduces tumor growth and tumor weight in human CRC xenograft tumors in nude mice. |
| Enzyme Assay |
Cell-free kinase assays using recombinant CDK2/cyclinE and CDK5/p35 proteins, incubated with varying compound concentrations and ATP. Activity measured via phosphorylation of histone H1 (CDK2) or pRb (CDK5) substrates using fluorescence polarization or radioactive methods.
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: CRC cell line SW620, DLD1, HT29, HCT116, FET, CBS and GEO Cell Tested Concentrations: 10 μM, 1 μM, 100 nM, 10 nM Incubation Duration: 72 hrs (hours) Experimental Results: diminished cell growth. The IC50 of SW620, DLD1, HT29, HCT116, FET, CBS and GEO cells were 168±20, 480±41, 360±72, 763±92, 117±49, 568±49, 79±31 nM. Western Blot Analysis[1] Cell Types: CRC cell lines GEO, HCT116 and HT29 Tested Concentrations: 20, 10, 5, 2.5, 1.25, 0.625, 0.3125 μM Incubation Duration: 6 hrs (hours) Experimental Results: Did not affect total levels of CDK2/5, and Levels of total FAK or total retinoblastoma protein (Rb). A dose-dependent decrease in pRB (S807/811) and pFAK (S732) levels was induced. CRC cell lines (SW620, DLD1, HT29, HCT116, etc.) treated with 20-223 (10 nM-10 uM; 72h). Cell viability assessed via standard assays (e.g., MTT). Western blotting for pRB and pFAK after 6h treatment at 0.3125-20 uM. |
| Animal Protocol |
Animal/Disease Models: athymic nude mice [1]
Doses: 8 mg/kg Route of Administration: subcutaneous injection every day in the first week, subcutaneous injection every other day for two weeks, a total of 14 injections. Experimental Results: In vivo tumor growth and tumor weight were diminished. Human CRC xenografts in athymic nude mice. Compound administered at 8 mg/kg via subcutaneous injection (daily first week, then every other day; total 14 injections). Tumor size and weight measured throughout study. |
| ADME/Pharmacokinetics |
Pharmacokinetic data not detailed in standard references; logP = 3.7; molecular weight 305.37; predicted high plasma protein binding. Oral bioavailability unknown; typical for tool compounds in pre-clinical development.
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| Toxicity/Toxicokinetics |
In mice, 20-223 (8 mg/kg, 3 weeks) significantly reduces tumor growth without observed toxicity, and lowers pFAK levels in tumors. No major adverse effects reported at this dose in xenograft models.
|
| References | |
| Additional Infomation |
Compound originally from Pfizer (CP668863) for neurodegenerative disorders, repurposed for CRC. Shown 3.5-fold and 65.3-fold more potent than AT7519 against CDK5 and CDK2, respectively. Not yet entered human clinical trials; ongoing research focuses on lead optimization for CRC therapy.
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| Molecular Formula |
C19H19N3O
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|---|---|
| Molecular Weight |
305.373664140701
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| Exact Mass |
305.152
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| CAS # |
865317-30-2
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| PubChem CID |
69761759
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| Appearance |
Light yellow to yellow solid powder
|
| LogP |
3.7
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
23
|
| Complexity |
423
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(CC1C=C2C(C=CC=C2)=CC=1)NC1C=C(C2CCC2)NN=1
|
| InChi Key |
AGVIDDQHAQSPIZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H19N3O/c23-19(20-18-12-17(21-22-18)15-6-3-7-15)11-13-8-9-14-4-1-2-5-16(14)10-13/h1-2,4-5,8-10,12,15H,3,6-7,11H2,(H2,20,21,22,23)
|
| Chemical Name |
N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-naphthalen-2-ylacetamide
|
| Synonyms |
CDK5 inhibitor 20223; CDK5 inhibitor 20 223
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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 : ~100 mg/mL (~327.47 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (16.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2747 mL | 16.3736 mL | 32.7472 mL | |
| 5 mM | 0.6549 mL | 3.2747 mL | 6.5494 mL | |
| 10 mM | 0.3275 mL | 1.6374 mL | 3.2747 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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