ArticleJournal of medicinal chemistry2013
Comparative structural and functional studies of 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile CDK9 inhibitors suggest the basis for isotype selectivity.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 68 citations in OpenAlex.
- First ATG101-recruiting small molecule degrader for selective CDK9 degradationActa pharmaceutica Sinica. B · 2025Article
- Characterization of 2,4-Dianilinopyrimidines Against FiveACS medicinal chemistry letters · 2023Article
- Design, synthesis and biological evaluation of 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives as CDK inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Targeting Transcriptional CDKs 7, 8, and 9 with Anilinopyrimidine Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and In Silico Studies.Molecules (Basel, Switzerland) · 2023Article
- CDK9 inhibitors in cancer research.RSC medicinal chemistry · 2022Review
- A Molecular Modeling Approach to Identify Potential Antileishmanial Compounds Against the Cell Division Cycle (cdc)-2-Related Kinase 12 (CRK12) Receptor ofBiomolecules · 2021Article
- Is Structure-Based Drug Design Ready for Selectivity Optimization?Journal of chemical information and modeling · 2020Article
- Therapeutic Targeting of the General RNA Polymerase II Transcription Machinery.International journal of molecular sciences · 2020Review
- Computational Simulations Identify Pyrrolidine-2,3-Dione Derivatives as Novel Inhibitors of Cdk5/p25 Complex to Attenuate Alzheimer's Pathology.Journal of clinical medicine · 2019Article
- Differences in the Conformational Energy Landscape of CDK1 and CDK2 Suggest a Mechanism for Achieving Selective CDK Inhibition.Cell chemical biology · 2019Article
- Structure-based discovery of cyclin-dependent protein kinase inhibitors.Essays in biochemistry · 2017Review
- Positive transcription elongation factor b (P-TEFb) is a therapeutic target in human multiple myeloma.Oncotarget · 2017Article
- The XChemExplorer graphical workflow tool for routine or large-scale protein-ligand structure determination.Acta crystallographica. Section D, Structural biology · 2017Article
- Cyclin Dependent Kinase 9 Inhibitors for Cancer Therapy.Journal of medicinal chemistry · 2016Article
- Overview of CDK9 as a target in cancer research.Cell cycle (Georgetown, Tex.) · 2016Review
- CDK1 structures reveal conserved and unique features of the essential cell cycle CDK.Nature communications · 2015Article
- Discovery of novel 5-fluoro-MedChemComm · 2015Article
- Determining the Functions of HIV-1 Tat and a Second Magnesium Ion in the CDK9/Cyclin T1 Complex: A Molecular Dynamics Simulation Study.PloS one · 2015Article
- Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73.Oncotarget · 2014Article
- Substituted 4-(thiazol-5-yl)-2-(phenylamino)pyrimidines are highly active CDK9 inhibitors: synthesis, X-ray crystal structures, structure-activity relationship, and anticancer activities.Journal of medicinal chemistry · 2013Article
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10 authors at 1 institution in 1 country.
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Abstract
Cyclin-dependent kinase 9/cyclin T, the protein kinase heterodimer that constitutes positive transcription elongation factor b, is a well-validated target for treatment of several diseases, including cancer and cardiac hypertrophy. In order to aid inhibitor design and rationalize the basis for CDK9 selectivity, we have studied the CDK-binding properties of six different members of a 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile series that bind to both CDK9/cyclin T and CDK2/cyclin A. We find that for a given CDK, the melting temperature of a CDK/cyclin/inhibitor complex correlates well with inhibitor potency, suggesting that differential scanning fluorimetry (DSF) is a useful orthogonal measure of inhibitory activity for this series. We have used DSF to demonstrate that the binding of these compounds is independent of the presence or absence of the C-terminal tail region of CDK9, unlike the binding of the CDK9-selective inhibitor 5,6-dichlorobenzimidazone-1-β-d-ribofuranoside (DRB). Finally, on the basis of 11 cocrystal structures bound to CDK9/cyclin T or CDK2/cyclin A, we conclude that selective inhibition of CDK9/cyclin T by members of the 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile series results from the relative malleability of the CDK9 active site rather than from the formation of specific polar contacts.
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