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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 |
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(S)-CR8 trihydrochloride, an analog of Roscovitine, is a novel, potent 2nd-generation cyclin-dependent kinase (CDK) inhibitor, also acting as a molecular glue degrader that depletes cyclin K. After experimental traumatic brain injury, it functions by reducing neuronal loss, astrocytosis, microglial activation, and neurologic dysfunction. [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) are all inhibited by (S)-CR8. The neuroprotective effect of (R)-CR8 is accompanied by apoptosis.
| 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)
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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]
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| 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]
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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.
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| Animal Protocol |
lateral fluid percussion-induced traumatic brain injury rats(male; Sprague-Dawley)
5 mg/Kg i.p. |
| References |
| Molecular Formula |
C₂₄H₃₂CL₃N₇O
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|---|---|
| Molecular Weight |
540.92
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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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| Appearance |
Solid powder
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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 |
| 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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