| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
CR8 targets multiple cyclin-dependent kinases (CDKs) and casein kinase 1 (CK1). It acts as an ATP-competitive inhibitor, binding to the ATP-binding pocket of these kinases. It inhibits CDK1, CDK2, CDK5, CDK7, CDK9, and CK1δ/ε with varying potencies. By inhibiting these kinases, it modulates cell cycle progression, transcription, and other cellular processes, leading to anticancer and neuroprotective effects.
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| ln Vitro |
(R)-CR8 (CR8) (0.1-100 μM; 48 hours) is a strong inducer of apoptosis with an IC50 of 0.49 μM in SH-SY5Y cell line [1]. (R)-CR8 (0.25-10 μM) promotes dose-dependent cleavage of poly(ADP-ribose) polymerase (PARP) [1]. The CDK-bound version of (R)-CR8 possesses a solvent-exposed pyridyl moiety that stimulates complex formation between CDK12-cyclin K and the CUL4 adaptor protein DDB1, bypassing the need for substrate receptors and presenting to the cell cycle Protein K suffers ubiquitination and destruction [3].
In vitro, CR8 is a potent inhibitor of CDK1/cyclin B (IC50 = 0.09 μM), CDK2/cyclin A (0.072 μM), CDK2/cyclin E (0.041 μM), CDK5/p25 (0.11 μM), CDK7/cyclin H (1.1 μM), CDK9/cyclin T (0.18 μM), and CK1δ/ε (0.4 μM). This broad inhibitory profile makes it a valuable tool for studying the role of these kinases in various cellular processes. It has anticancer and neuroprotective effects. |
| ln Vivo |
(R)-CR8 (5 mg/Kg; intraperitoneal injection) significantly reduced the size of the lesion at 28 days in histological examination [2].
In vivo activity data for CR8 is limited. As a potent CDK inhibitor, it is expected to have antitumor effects in animal models. It has been studied for its neuroprotective effects. However, specific in vivo study details are not well-documented. It is primarily used as a research tool to study the function of CDKs and CK1. |
| Enzyme Assay |
CR8 is evaluated in cell-free kinase assays using purified CDK and CK1 enzymes. The compound is incubated with the kinase, ATP, and a substrate, and the inhibition of kinase activity is measured. IC50 values are determined to quantify the potency of kinase inhibition. Its selectivity profile can be assessed by screening against a panel of kinases.
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| Cell Assay |
Apoptosis analysis [1]
Cell Types: SH-SY5Y Cell line Tested Concentrations: 0.1, 1, 10, 100 μM Incubation Duration: 24 hrs (hours) Experimental Results: Cell survival rate diminished in a dose-dependent manner. CR8 is assessed in cell-based assays using various cancer cell lines and neuronal cells. Cells are treated with CR8, and cell cycle progression, apoptosis, and cell proliferation are measured. Its neuroprotective effects are evaluated in models of neurodegeneration. The compound's ability to inhibit CDK and CK1 activity in a cellular context is confirmed by measuring the phosphorylation of downstream targets. |
| Animal Protocol |
Animal/Disease Models: Adult (10 to 12 weeks old) male SD (SD (Sprague-Dawley)) rats (310 to 330 g) [2]
Doses: ip Route of Administration: 5 mg/Kg Experimental Results: Results in a significant reduction in lesion size. CR8 is administered in animal models to evaluate its effects on tumor growth and neuroprotection. However, specific animal study protocols are not extensively documented. It is typically formulated for in vivo administration using DMSO or other suitable vehicles. Its efficacy in models of cancer or neurodegenerative diseases is of research interest. |
| ADME/Pharmacokinetics |
CR8 has a molecular formula of C24H29N7O and a molecular weight of 431.53. Its CAS number is 294646-77-8. The compound is a solid. It should be stored under recommended conditions. It is also known as (R)-CR8.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is available for CR8. The compound is for research use only and is not intended for human therapeutic use. It is a potent CDK/CK1 inhibitor used as a research tool to study cell cycle regulation and neuroprotection.
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| References |
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| Additional Infomation |
CR8 is a potent and selective inhibitor of CDKs and CK1. It is a second-generation analog of roscovitine. It has anticancer and neuroprotective effects. The compound is not approved for clinical use.
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| Molecular Formula |
C24H29N7O
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|---|---|
| Molecular Weight |
431.53
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| Exact Mass |
431.243
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| CAS # |
294646-77-8
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| Related CAS # |
(S)-CR8;1084893-56-0;(R)-CR8 trihydrochloride;1786438-30-9
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| PubChem CID |
10224714
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
671.4±65.0 °C at 760 mmHg
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| Flash Point |
359.8±34.3 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.664
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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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
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| InChi Key |
HOCBJBNQIQQQGT-LJQANCHMSA-N
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| InChi Code |
InChI=1S/C24H29N7O/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)/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
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| Synonyms |
CR 8 CR-8 CR8
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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 : ~50 mg/mL (~115.87 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 | 2.3173 mL | 11.5867 mL | 23.1734 mL | |
| 5 mM | 0.4635 mL | 2.3173 mL | 4.6347 mL | |
| 10 mM | 0.2317 mL | 1.1587 mL | 2.3173 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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