CR8 hydrochloride
CR8 is a potent and selective inhibitor of CDK. CR8 is a more potent pyridyl analogue of roscovitine. 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.
For research use only. We do not sell to patients.
Chemical Information
| Name | CR8 hydrochloride |
|---|---|
| Iupac Chemical Name | (R)-2-((9-isopropyl-6-((4-(pyridin-2-yl)benzyl)amino)-9H-purin-2-yl)amino)butan-1-ol trihydrochloride |
| Synonyms | (R)-CR8; (R)-CR-8; (R)-CR 8; CR8; CR-8; CR 8; CR8 CDK inhibitor; CR8 CDK inhibitor HCl; CR8 CDK inhibitor hydrochloride; (R)-CR8 trihydrochloride; |
| Molecular Formula | C24H32Cl3N7O |
| Molecular Weight | 540.92 |
| Smile | CC[C@@H](NC1=NC(NCC2=CC=C(C3=NC=CC=C3)C=C2)=C4N=CN(C(C)C)C4=N1)CO.[H]Cl.[H]Cl.[H]Cl |
| InChiKey | ORYSYXHQFOWNDK-RGFWRHHQSA-N |
| InChi | 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 |
| CAS Number | 1786438-30-9 |
| Related CAS |
Ordering Information
| Packaging | Price | Availability | Purity | Shipping Time |
|---|---|---|---|---|
| Bulk | Enquiry | Enquiry | Enquiry |
| Formulation | Solid powder |
|---|---|
| Purity | 98% Min. |
| Storage | Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Solubility | Soluble in DMSO |
| Handling | |
| Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
| HS Code |
| Targets | |
|---|---|
| Mechanism | |
| Cell study | |
| Animal study | |
| Clinical study |
1: Słabicki M, Kozicka Z, Petzold G, Li YD, Manojkumar M, Bunker RD, Donovan KA, Sievers QL, Koeppel J, Suchyta D, Sperling AS, Fink EC, Gasser JA, Wang LR, Corsello SM, Sellar RS, Jan M, Gillingham D, Scholl C, Fröhling S, Golub TR, Fischer ES, Thomä NH, Ebert BL. The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K. Nature. 2020 Jun 3. doi: 10.1038/s41586-020-2374-x. Epub ahead of print. PMID: 32494016.
2: Bettayeb K, Oumata N, Echalier A, Ferandin Y, Endicott JA, Galons H, Meijer L. CR8, a potent and selective, roscovitine-derived inhibitor of cyclin- dependent kinases. Oncogene. 2008 Oct 2;27(44):5797-807. doi: 10.1038/onc.2008.191. Epub 2008 Jun 23. PMID: 18574471.
3: Kabadi SV, Stoica BA, Hanscom M, Loane DJ, Kharebava G, Murray Ii MG, Cabatbat RM, Faden AI. CR8, a selective and potent CDK inhibitor, provides neuroprotection in experimental traumatic brain injury. Neurotherapeutics. 2012 Apr;9(2):405-21. doi: 10.1007/s13311-011-0095-4. PMID: 22167461; PMCID: PMC3324621.
4: Sallam H, El-Serafi I, Meijer L, Hassan M. Pharmacokinetics and biodistribution of the cyclin-dependent kinase inhibitor -CR8- in mice. BMC Pharmacol Toxicol. 2013 Sep 30;14:50. doi: 10.1186/2050-6511-14-50. PMID: 24079553; PMCID: PMC3849647.
5: Bettayeb K, Baunbæk D, Delehouze C, Loaëc N, Hole AJ, Baumli S, Endicott JA, Douc-Rasy S, Bénard J, Oumata N, Galons H, Meijer L. CDK Inhibitors Roscovitine and CR8 Trigger Mcl-1 Down-Regulation and Apoptotic Cell Death in Neuroblastoma Cells. Genes Cancer. 2010 Apr;1(4):369-80. doi: 10.1177/1947601910369817. PMID: 21779453; PMCID: PMC3092200.
6: Goulding SP, de Guglielmo G, Carrette LLG, George O, Contet C. Systemic Administration of the Cyclin-Dependent Kinase Inhibitor (S)-CR8 Selectively Reduces Escalated Ethanol Intake in Dependent Rats. Alcohol Clin Exp Res. 2019 Oct;43(10):2079-2089. doi: 10.1111/acer.14177. Epub 2019 Aug 30. PMID: 31403700; PMCID: PMC6779498.
7: Beadling C, Cereseto A, Fan W, Naramura M, Smith KA. Cytokine response gene 8 (CR8) regulates the cell cycle G1-S phase transition and promotes cellular survival. Oncogene. 2001 Mar 29;20(14):1771-83. doi: 10.1038/sj.onc.1204212. PMID: 11313924.
8: Troadec S, Blairvacq M, Oumata N, Galons H, Meijer L, Berthou C. Antitumoral effects of cyclin-dependent kinases inhibitors CR8 and MR4 on chronic myeloid leukemia cell lines. J Biomed Sci. 2015 Jul 17;22(1):57. doi: 10.1186/s12929-015-0163-x. PMID: 26184865; PMCID: PMC4504225.
9: Delehouzé C, Godl K, Loaëc N, Bruyère C, Desban N, Oumata N, Galons H, Roumeliotis TI, Giannopoulou EG, Grenet J, Twitchell D, Lahti J, Mouchet N, Galibert MD, Garbis SD, Meijer L. CDK/CK1 inhibitors roscovitine and CR8 downregulate amplified MYCN in neuroblastoma cells. Oncogene. 2014 Dec 11;33(50):5675-87. doi: 10.1038/onc.2013.513. Epub 2013 Dec 9. PMID: 24317512; PMCID: PMC4087096.
10: Kabadi SV, Stoica BA, Loane DJ, Luo T, Faden AI. 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. doi: 10.1038/jcbfm.2013.228. Epub 2014 Jan 8. PMID: 24398934; PMCID: PMC3948132.
11: Billot K, Coquil C, Villiers B, Josselin-Foll B, Desban N, Delehouzé C, Oumata N, Le Meur Y, Boletta A, Weimbs T, Grosch M, Witzgall R, Saunier S, Fischer E, Pontoglio M, Fautrel A, Mrug M, Wallace D, Tran PV, Trudel M, Bukanov N, Ibraghimov-Beskrovnaya O, Meijer L. Casein kinase 1ε and 1α as novel players in polycystic kidney disease and mechanistic targets for (R)-roscovitine and (S)-CR8. Am J Physiol Renal Physiol. 2018 Jul 1;315(1):F57-F73. doi: 10.1152/ajprenal.00489.2017. Epub 2018 Mar 14. PMID: 29537311; PMCID: PMC6087785.
12: Cosimo E, McCaig AM, Carter-Brzezinski LJ, Wheadon H, Leach MT, Le Ster K, Berthou C, Durieu E, Oumata N, Galons H, Meijer L, Michie AM. Inhibition of NF- κB-mediated signaling by the cyclin-dependent kinase inhibitor CR8 overcomes prosurvival stimuli to induce apoptosis in chronic lymphocytic leukemia cells. Clin Cancer Res. 2013 May 1;19(9):2393-405. doi: 10.1158/1078-0432.CCR-12-2170. Epub 2013 Mar 26. PMID: 23532892.
13: Liu YY, Wang GP, Peng Z, Guo JY, Wu Q, Xie J, Gong SS. E2F1-CDK1 pathway activation in kanamycin-induced spiral ganglion cell apoptosis and the protective effect of CR8. Neurosci Lett. 2016 Mar 23;617:247-53. doi: 10.1016/j.neulet.2016.02.034. Epub 2016 Feb 22. PMID: 26905670.
14: Toribio AL, Pickard D, Cerdeño-Tárraga AM, Petty NK, Thomson N, Salmond G, Dougan G. Complete Genome Sequences of Two Citrobacter rodentium Bacteriophages, CR8 and CR44b. Genome Announc. 2014 May 29;2(3):e00146-14. doi: 10.1128/genomeA.00146-14. PMID: 24874665; PMCID: PMC4038870.
15: Huang BY, Huang HB, Zhang ZJ, Liu ZG, Luo J, Liu M, Luo T. Cell cycle activation contributes to isoflurane-induced neurotoxicity in the developing brain and the protective effect of CR8. CNS Neurosci Ther. 2019 May;25(5):612-620. doi: 10.1111/cns.13090. Epub 2019 Jan 24. PMID: 30676695; PMCID: PMC6488878.
16: Bukanov NO, Moreno SE, Natoli TA, Rogers KA, Smith LA, Ledbetter SR, Oumata N, Galons H, Meijer L, Ibraghimov-Beskrovnaya O. CDK inhibitors R-roscovitine and S-CR8 effectively block renal and hepatic cystogenesis in an orthologous model of ADPKD. Cell Cycle. 2012 Nov 1;11(21):4040-6. doi: 10.4161/cc.22375. Epub 2012 Oct 3. PMID: 23032260; PMCID: PMC3507499.
17: Kobayashi Y, Watanabe T, Inoue Y, Arakawa H, Mochizuki H, Tokuyama K, Morikawa A. CR8-194--A case of fulminated fatal disseminated Varicella Zoster virus infection with severe pulmonary damage. Paediatr Respir Rev. 2006;7 Suppl 1:S328. doi: 10.1016/j.prrv.2006.04.148. PMID: 17036409.
18: Baker ML, Lancaster T, Chiesa A, Amoretti G, Baker PJ, Barker C, Blundell SJ, Carretta S, Collison D, Güdel HU, Guidi T, McInnes EJ, Möller JS, Mutka H, Ollivier J, Pratt FL, Santini P, Tuna F, Tregenna-Piggott PL, Vitorica-Yrezabal IJ, Timco GA, Winpenny RE. Studies of a Large Odd-Numbered Odd-Electron Metal Ring: Inelastic Neutron Scattering and Muon Spin Relaxation Spectroscopy of Cr8 Mn. Chemistry. 2016 Jan 26;22(5):1779-88. doi: 10.1002/chem.201503431. Epub 2016 Jan 8. PMID: 26748964; PMCID: PMC4744977.
19: Vaknin D, Garlea VO, Demmel F, Mamontov E, Nojiri H, Martin C, Chiorescu I, Qiu Y, Kögerler P, Fielden J, Engelhardt L, Rainey C, Luban M. Level crossings and zero-field splitting in the {Cr8}-cubane spin cluster studied using inelastic neutron scattering and magnetization. J Phys Condens Matter. 2010 Nov 24;22(46):466001. doi: 10.1088/0953-8984/22/46/466001. Epub 2010 Oct 29. PMID: 21403379.
20: Waldmann O, Guidi T, Carretta S, Mondelli C, Dearden AL. Elementary excitations in the cyclic molecular nanomagnet Cr8. Phys Rev Lett. 2003 Dec 5;91(23):237202. doi: 10.1103/PhysRevLett.91.237202. Epub 2003 Dec 4. PMID: 14683210.
Chemical Structure
