294646-77-8 Usage
Description
2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-(4-(2-pyridyl)benzyl)-9-isopropylpurinetrihydrochloride, also known as CR8, is a second-generation analog of roscovitine with increased potency in inhibiting cyclin-dependent kinases (CDKs) and casein kinase 1 (CK1). It is a cell-permeable, ATP-binding pocket-targeting CDK/CK1 dual-specific inhibitor that acts as a molecular glue degrader, depleting cyclin K and displaying neuroprotective effects in various models, including traumatic brain injury.
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 articles and documents
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.