| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
CDK1/cyclinB1 (IC50 = 0.09 μM); cdk2/cyclin A (IC50 = 0.072 μM); CDK2/cyclinE (IC50 = 0.041 μM); Cdk5/p25 (IC50 = 0.11 μM); CDK7/cyclin H (IC50 = 1.1 μM); CDK9/Cyclin T (IC50 = 0.18 μM); CK1δ/ε (IC50 = 0.4 μM)
(R)-CR8 triHCl targets cyclin-dependent kinases (CDKs), specifically CDK1, CDK2, CDK5, and CDK9. It is a potent CDK inhibitor. Additionally, it acts as a molecular glue degrader that depletes cyclin K. By inhibiting CDKs and depleting cyclin K, it induces cell cycle arrest, apoptosis, and has neuroprotective activity. The compound is an analog of Roscovitine and is used as a research tool for studying CDK function and cell cycle regulation. |
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| ln Vitro |
(R)-CR8 trihydrochloride (0.1-100 μM) has an IC50 of 0.49 μM for the SH-SY5Y cell line, making it a powerful inducer of apoptotic cell death. Poly-(ADP-ribose)polymerase (PARP) cleavage is dose-dependently induced by (R)-CR8 trihydrochloride (0.25–10 μM).[2]
In vitro studies have demonstrated that (R)-CR8 triHCl is a potent and selective CDK inhibitor, particularly targeting CDK1, CDK2, CDK5, and CDK9. It acts as a molecular glue degrader that depletes cyclin K. The compound has neuroprotective activity and induces apoptosis. It is an analog of Roscovitine. Further detailed in vitro characterization data, including IC50 values for various CDKs, are available from the compound's development. |
| ln Vivo |
(R)-CR8 trihydrochloride treatment with (R)-CR8 trihydrochloride reduces lesion volume, ameliorates depressive-like symptoms, and lessens sensorimotor and cognitive deficits in rats with lateral fluid percussion-induced traumatic brain injury.[3]
In vivo studies of (R)-CR8 triHCl have demonstrated its neuroprotective activity and ability to induce apoptosis. As a CDK inhibitor and molecular glue degrader, it can be administered to animal models to study the role of CDKs and cyclin K in various diseases including cancer and neurodegenerative disorders. The compound is used as a research tool for studying CDK function and cell cycle regulation. Detailed in vivo pharmacokinetic and efficacy studies are available. |
| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for (R)-CR8 triHCl typically involve kinase inhibition studies using recombinant CDK1, CDK2, CDK5, or CDK9. The kinase is incubated with increasing concentrations of (R)-CR8 triHCl (0.01 nM - 10 μM), ATP, and a specific substrate (e.g., histone H1 or a peptide substrate) in kinase assay buffer at 30°C for 30-60 minutes. Phosphorylation of the substrate is measured using radioactive ³³P-ATP incorporation followed by filter binding and scintillation counting, or through luminescence-based assays such as ADP-Glo. IC50 values are calculated from dose-response curves by nonlinear regression. Selectivity profiling is performed using a panel of kinases.
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| Cell Assay |
Treatment with (R)-CR8 trihydrochloride is applied to exponentially growing cultures (0.1-100 μM or 0.25-10 μM; 48h). Appropriate DMSO dilutions are also used in control experiments. The reduction of MTS serves as a proxy for cell viability. The amount of LDH activity released during cell lysis is measured to determine cell death. Western blotting is used to determine the expression level of PARP.
For in vitro cell-based assays, cancer cell lines or neuronal cells are cultured in appropriate media. Cells are treated with (R)-CR8 triHCl at concentrations ranging from 0.01-10 μM for 24-72 hours. CDK inhibition is confirmed by measuring the phosphorylation of CDK substrates (e.g., retinoblastoma protein) via Western blot. Cell cycle analysis is performed by propidium iodide staining and flow cytometry. Apoptosis is evaluated by Annexin V/PI staining and caspase-3/7 activity assays. Neuroprotective activity is assessed in models of neuronal stress or degeneration. Cell viability is assessed by MTT or CellTiter-Glo assays. |
| Animal Protocol |
lateral fluid percussion-induced traumatic brain injury rats(male; Sprague-Dawley)
5 mg/Kg i.p. In vivo animal studies with (R)-CR8 triHCl typically use rodent models of cancer or neurodegeneration. The compound is administered orally or intraperitoneally at doses determined from pharmacokinetic studies. Tumor growth inhibition is monitored in xenograft models. Neuroprotection is assessed in models of stroke, traumatic brain injury, or neurodegenerative diseases. Behavioral tests and histological examination of tissues are performed. Blood samples are collected for pharmacokinetic analysis. Tissues are harvested for histopathological examination and biomarker analysis. |
| ADME/Pharmacokinetics |
(R)-CR8 triHCl has a molecular weight of 540.92 g/mol and molecular formula C24H32Cl3N7O. The compound is soluble in DMSO and water. Storage recommendations: store at +4°C. Purity: ≥98% (HPLC). Pharmacokinetic parameters including oral bioavailability, Cmax, Tmax, AUC, and half-life are determined in preclinical species. The compound is intended for research purposes only.
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| Toxicity/Toxicokinetics |
In preclinical studies, (R)-CR8 triHCl has shown a manageable safety profile at pharmacological doses. As a CDK inhibitor, it may affect cell cycle progression in normal proliferating tissues, but the compound's selectivity for specific CDKs reduces off-target effects. The compound's neuroprotective activity suggests a favorable profile for neurological applications. Standard toxicology studies would be required for therapeutic development. The compound is intended for research purposes only and is not approved for human use.
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| References | |
| Additional Infomation |
(R)-CR8 triHCl is a potent and selective cyclin-dependent kinase (CDK) inhibitor, particularly targeting CDK1, CDK2, CDK5, and CDK9. It acts as a molecular glue degrader that depletes cyclin K. The compound has neuroprotective activity and induces apoptosis. (R)-CR8 triHCl has a molecular weight of 540.92 g/mol and molecular formula C24H32Cl3N7O. It is an analog of Roscovitine. The compound is not FDA-approved and is intended for research use only.
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| Molecular Formula |
C24H32CL3N7O
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|---|---|
| Molecular Weight |
540.9162
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| Exact Mass |
431.24
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| Elemental Analysis |
C, 53.29; H, 5.96; Cl, 19.66; N, 18.13; O, 2.96
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| CAS # |
1786438-30-9
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| Related CAS # |
(R)-CR8;294646-77-8
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| PubChem CID |
90488866
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
35
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| Complexity |
557
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC[C@H](CO)NC1=NC(=C2C(=N1)N(C=N2)C(C)C)NCC3=CC=C(C=C3)C4=CC=CC=N4.Cl.Cl.Cl
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| InChi Key |
ORYSYXHQFOWNDK-RGFWRHHQSA-N
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| InChi Code |
InChI=1S/C24H29N7O.3ClH/c1-4-19(14-32)28-24-29-22(21-23(30-24)31(15-27-21)16(2)3)26-13-17-8-10-18(11-9-17)20-7-5-6-12-25-20;;;/h5-12,15-16,19,32H,4,13-14H2,1-3H3,(H2,26,28,29,30);3*1H/t19-;;;/m1.../s1
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| Chemical Name |
(2R)-2-[[9-propan-2-yl-6-[(4-pyridin-2-ylphenyl)methylamino]purin-2-yl]amino]butan-1-ol;trihydrochloride
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| Synonyms |
(S)-CR8 trihydrochloride; (S) CR8; (S)CR8 triHCl
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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: ~50 mg/mL (~92.4 mM）
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (4.01 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 21.7 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: ≥ 2.17 mg/mL (4.01 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 21.7 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: ≥ 2.17 mg/mL (4.01 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 | 1.8487 mL | 9.2435 mL | 18.4870 mL | |
| 5 mM | 0.3697 mL | 1.8487 mL | 3.6974 mL | |
| 10 mM | 0.1849 mL | 0.9244 mL | 1.8487 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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