| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
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| Targets |
PNU112455A HCl targets cyclin-dependent kinase 2 (CDK2) and cyclin-dependent kinase 5 (CDK5). CDK2 is a key regulator of the cell cycle, particularly the G1/S transition, and is often dysregulated in cancer. CDK5 is involved in neuronal signaling and has been implicated in neurodegenerative diseases. PNU112455A HCl is an ATP-competitive inhibitor that binds to the ATP-binding site of both kinases.
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| ln Vitro |
PNU112455A HCl demonstrates potent inhibition of CDK2 and CDK5 with Km values of 3.6 and 3.2 μM, respectively. It binds to the ATP site of both kinases in an ATP-competitive manner. It inhibits hyperphosphorylation of tau in vitro. It also inhibits cell death induced by dexamethasone. The compound's selectivity for CDK2 and CDK5 over other kinases has been characterized.
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| ln Vivo |
PNU112455A HCl has been studied in vivo for its effects on tau phosphorylation and neurodegeneration. It inhibits hyperphosphorylation of tau and cell death induced by dexamethasone. Its potential therapeutic applications include neurodegenerative diseases where CDK5 dysregulation plays a role. Detailed in vivo efficacy data are limited in publicly available sources.
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| Enzyme Assay |
CDK2 and CDK5 kinase activity assays are performed using recombinant human CDK2/cyclin E or CDK5/p25 complexes. The enzyme is incubated with a peptide substrate (e.g., histone H1) and [γ-32P]ATP or fluorescently labeled ATP in kinase buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT). The reaction is incubated at 30°C for 30-60 minutes. Phosphorylated substrate is quantified by scintillation counting or fluorescence polarization. Test compounds are serially diluted and added to the reaction mixture. IC50 or Ki values are determined by non-linear regression analysis. Each concentration is tested in duplicate.
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| Cell Assay |
Cellular CDK2 and CDK5 inhibition is evaluated in neuronal cell lines (e.g., SH-SY5Y, PC12) or cancer cell lines. Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with PNU112455A HCl at various concentrations (0.1-100 μM) for 24-72 hours. CDK2 and CDK5 activity in cell lysates is measured using kinase assays. Tau phosphorylation is measured by Western blotting using phospho-specific antibodies (e.g., AT8 for pSer202/Thr205). Cell viability is assessed using MTT or LDH assays. Apoptosis is evaluated by caspase-3/7 activity. Each experiment includes known CDK inhibitors (e.g., roscovitine) as positive controls.
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| Animal Protocol |
In vivo efficacy is evaluated in animal models of neurodegeneration or tauopathy. PNU112455A HCl is administered orally or intraperitoneally at doses determined by preclinical studies. Tau phosphorylation is measured in brain tissue by Western blotting. Behavioral assessments may include tests of motor function and cognition. Neurodegeneration is assessed by histology and measurement of neuronal loss. Sample sizes typically range from 8-12 animals per group. Detailed protocols are not publicly available.
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| ADME/Pharmacokinetics |
PNU112455A HCl has a molecular weight of 301.76 g/mol and a molecular formula of C10H12ClN5O2S. Storage: store at -20°C. Solubility: DMSO. Bioavailability, half-life, and tissue distribution data are not publicly available. The compound is a research tool for studying CDK2 and CDK5 function.
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| Toxicity/Toxicokinetics |
Limited toxicology data are available for PNU112455A HCl. As a CDK inhibitor, potential toxicities may include effects on cell cycle regulation and neuronal function. Standard toxicology studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on the nervous system. No clinical trials have been reported for this compound. The compound is intended for research use only.
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| References |
: Monaco EA 3rd, Beaman-Hall CM, Mathur A, Vallano ML. Roscovitine, olomoucine, purvalanol: inducers of apoptosis in maturing cerebellar granule neurons. Biochem Pharmacol. 2004 May 15;67(10):1947-64.
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| Additional Infomation |
PNU112455A HCl is also known as PNU 112455A hydrochloride. It is an ATP-competitive inhibitor of CDK2 and CDK5 with Km values of 3.6 and 3.2 μM, respectively. It inhibits tau hyperphosphorylation and dexamethasone-induced cell death. It is used for research on cell cycle regulation and neurodegeneration. No clinical trials or regulatory approvals have been reported. The compound is for research use only.
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| Molecular Formula |
C10H12CLN5O2S
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|---|---|
| Molecular Weight |
301.749
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| Exact Mass |
301.04
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| CAS # |
21886-12-4
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| Related CAS # |
400611-95-2;21886-12-4 (HCl);
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| PubChem CID |
16760362
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.532g/cm3
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| Boiling Point |
568.6ºC at 760 mmHg
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| Flash Point |
297.7ºC
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| Vapour Pressure |
6.04E-13mmHg at 25°C
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| Index of Refraction |
1.697
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| LogP |
3.687
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
19
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| Complexity |
361
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
XBXQRCJKDCEQBS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H11N5O2S.ClH/c11-9-5-10(14-6-13-9)15-7-1-3-8(4-2-7)18(12,16)17/h1-6H,(H2,12,16,17)(H3,11,13,14,15)1H
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| Chemical Name |
4-[(6-aminopyrimidin-4-yl)amino]benzenesulfonamide;hydrochloride
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| Synonyms |
PNU 112455A HCl PNU-112455A PNU112455A
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~125 mg/mL (~414.25 mM)
H2O : ~20 mg/mL (~66.28 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.89 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.89 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.89 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3140 mL | 16.5700 mL | 33.1400 mL | |
| 5 mM | 0.6628 mL | 3.3140 mL | 6.6280 mL | |
| 10 mM | 0.3314 mL | 1.6570 mL | 3.3140 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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