294646-77-8 Usage
Uses
Used in Pharmaceutical Industry:
2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-(4-(2-pyridyl)benzyl)-9-isopropylpurinetrihydrochloride is used as a CDK/CK1 dual-specific inhibitor for its ability to inhibit cyclin-dependent kinases with increased potency, making it a potential candidate for the development of therapeutic agents targeting various diseases.
Used in Neuroprotection:
In the field of neuroprotection, 2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-(4-(2-pyridyl)benzyl)-9-isopropylpurinetrihydrochloride is used as a neuroprotective agent due to its ability to display neuroprotective effects in various models, including traumatic brain injury, offering potential therapeutic benefits for treating neurological disorders and injuries.
Biochem/physiol Actions
CR8 is a potent and selective inhibitor of cyclin dependent kinase (CDK1, 2, 5, 7, and 9). CR8 is a more potent pyridyl analogue of roscovitine (Cat. No. R7772). In comparison to roscovirtine, the compound gains in potency toward CK1, which is involved in amyloid-β formation. The R-CR8 enantiomer is slightly more potent than S. CR8 is around 30 times more potent at cellular assay then roscovitine. Acts as a molecular glue to induce cyclin K degradation.
References
Bettayeb et al. (2008), C8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases; Oncogene, 27 5797
Bettayeb et al. (2010), CDK Inhibitors Roscovitine and CR8 Trigger Mcl-1 Down-Regulation and Apoptotic Cell Death in Neuroblastoma Cells; Genes Cancer, 1 369
Slabiki et al. (2020), The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K; Nature, 585 293
Aubrecht et al. (2018), Comparing effects of CDK inhibitor and E2F1/2 ablation on neuronal cell death pathways in vitro and after traumatic brain injury; Cell Death Dis., 9 112
Check Digit Verification of cas no
The CAS Registry Mumber 294646-77-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,9,4,6,4 and 6 respectively; the second part has 2 digits, 7 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 294646-77:
(8*2)+(7*9)+(6*4)+(5*6)+(4*4)+(3*6)+(2*7)+(1*7)=188
188 % 10 = 8
So 294646-77-8 is a valid CAS Registry Number.
294646-77-8Relevant academic research and scientific papers
Practical synthesis of roscovitine and CR8
Oumata, Nassima,Ferandin, Yoan,Meijer, Laurent,Galons, Herve
experimental part, p. 641 - 644 (2010/04/22)
Roscovitine and CR8 are potent inhibitors of cyclin-dependent kinases. A scalable synthesis of both inhibitors is described. In the case of CR8, the biarylmethylamine moiety was obtained as a stable and high-purity salt.
Roscovitine-derived, dual-specificity inhibitors of cyclin-dependent kinases and casein kinases 1
Oumata, Nassima,Bettayeb, Karima,Ferandin, Yoan,Demange, Luc,Lopez-Giral, Angela,Goddard, Marie-Lorène,Myrianthopoulos, Vassilios,Mikros, Emmanuel,Flajolet, Marc,Greengard, Paul,Meijer, Laurent,Galons, Hervé
experimental part, p. 5229 - 5242 (2009/07/01)
Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-β peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC50: 220 nM), CDK5/p25 (IC50: 80 nM), and CK1 (IC 50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1δ provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of amyloid-β in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.
