Cdk4 inhibitor III   Click here for help

GtoPdb Ligand ID: 5952

Synonyms: ryuvidine
Compound class: Synthetic organic
Comment: CDK4 inhibitor III (ryuvidine), as its name suggests was originally reported as a selective inhibitor of CDK4, albeit a weak inhibitor [6]. However, to date (October 2018) there is no published data showing cellular inhibition of CDK4 by this compound, but some evidence of action at another target(s) that regulates the S phase of the cell cycle has been reported [5]. This latter effect may be due to CDK4 inhibitor III-induced inhibition of the lysine methyltransferase SETD8 [2,4].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 2
Topological polar surface area 87.3
Molecular weight 284.06
XLogP 2.2
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES Cc1ccc(cc1)NC1=CC(=O)c2c(C1=O)nc(s2)C
Isomeric SMILES Cc1ccc(cc1)NC1=CC(=O)c2c(C1=O)nc(s2)C
InChI InChI=1S/C15H12N2O2S/c1-8-3-5-10(6-4-8)17-11-7-12(18)15-13(14(11)19)16-9(2)20-15/h3-7,17H,1-2H3
InChI Key HFPLHASLIOXVGS-UHFFFAOYSA-N
References
1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011)
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
Nat. Biotechnol., 29 (11): 1039-45. [PMID:22037377]
2. Blum G, Ibáñez G, Rao X, Shum D, Radu C, Djaballah H, Rice JC, Luo M. (2014)
Small-molecule inhibitors of SETD8 with cellular activity.
ACS Chem. Biol., 9 (11): 2471-8. [PMID:25137013]
3. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013)
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
Biochem. J., 451 (2): 313-28. [PMID:23398362]
4. Houston SI, McManus KJ, Adams MM, Sims JK, Carpenter PB, Hendzel MJ, Rice JC. (2008)
Catalytic function of the PR-Set7 histone H4 lysine 20 monomethyltransferase is essential for mitotic entry and genomic stability.
J. Biol. Chem., 283 (28): 19478-88. [PMID:18480059]
5. Jorda R, Hendrychová D, Voller J, Řezníčková E, Gucký T, Kryštof V. (2018)
How Selective Are Pharmacological Inhibitors of Cell-Cycle-Regulating Cyclin-Dependent Kinases?.
J. Med. Chem., 61 (20): 9105-9120. [PMID:30234987]
6. Ryu CK, Kang HY, Lee SK, Nam KA, Hong CY, Ko WG, Lee BH. (2000)
5-Arylamino-2-methyl-4,7-dioxobenzothiazoles as inhibitors of cyclin-dependent kinase 4 and cytotoxic agents.
Bioorg. Med. Chem. Lett., 10 (5): 461-4. [PMID:10743948]