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CR8 is a novel and potent inhibitor of CDK with anticancer and neuroprotective effects. As a second-generation analog of Roscovitine, (R)-CR8 (CR8) inhibits 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).
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].
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ln Vivo |
(R)-CR8 (5 mg/Kg; intraperitoneal injection) significantly reduced the size of the lesion at 28 days in histological examination [2].
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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. |
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. |
References |
[1]. Bettayeb K, et al. CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases. Oncogene. 2008 Oct 2;27(44):5797-807.
[2]. Kabadi SV, et al. CR8, a novel inhibitor of CDK, limits microglial activation, astrocytosis, neuronal loss, and neurologic dysfunction after experimental traumatic brain injury. J Cereb Blood Flow Metab. 2014 Mar;34(3):502-13. [3]. Słabicki M, et al. The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K [published online ahead of print, 2020 Jun 3]. Nature. 2020;10.1038/s41586-020-2374-x. |
Molecular Formula |
C24H29N7O
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Molecular Weight |
431.53
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Exact Mass |
431.24336
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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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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
CC[C@H](CO)N=C1NC(=C2C(=N1)N(C=N2)C(C)C)NCC3=CC=C(C=C3)C4=CC=CC=N4
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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.