Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Structure-activity relationships have been developed around 5-bromo-8-toluylsulfonamidoquinoline 1 a hit compound in an assay for the interaction of the E3 ligase Skp2 with Cks1, part of the SCF ligase complex. Disruption of this protein-protein interaction results in higher levels of CDK inhibitor p27, which can act as a tumor suppressor. The results of the SAR developed highlight the relationship between the sulfonamide and quinoline nitrogen, while also suggesting that an aryl substituent at the 5-position of the quinoline ring contributes to the potency in the interaction assay. Compounds showing potency in the interaction assay result in greater levels of p27 and have been shown to inhibit cell growth of two p27 sensitive tumor cell lines.
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PMID:Developing structure-activity relationships from an HTS hit for inhibition of the Cks1-Skp2 protein-protein interaction. 2646 31

In plants, the calmodulin-binding transcription activators (CAMTAs) are required for transcriptional regulation of abiotic and biotic stress responses. Among them, CAMTA3 in Arabidopsis has been intensively studied and shown to function redundantly with CAMTA1 and CAMTA2 to negatively regulate plant immunity. The camta1/2/3 triple mutant accordingly exhibits severe dwarfism due to autoimmunity. Here, through a suppressor screen using camta1/2/3 triple mutant, we found that a mutation in Cyclin-Dependent Kinase 8 (CDK8) partially suppresses the dwarfism and constitutive resistance phenotypes of camta1/2/3. CDK8 positively regulates steady-state salicylic acid (SA) levels and systemic required resistance (SAR). The expression of SA biosynthesis genes such as ICS1 and EDS5 is down-regulated in cdk8 mutants under uninfected conditions, suggesting that CDK8 contributes to the transcriptional regulation of these SA pathway genes. Knocking out another Mediator kinase module member MED12 yielded similar defects including decreased steady-state SA level and compromised SAR, suggesting that the whole Mediator kinase module contributes to the transcriptional regulation of SA levels and SAR.
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PMID:The Mediator kinase module serves as a positive regulator of salicylic acid accumulation and systemic acquired resistance. 3073 57

The TAIRE family of kinases are an understudied branch of the CDK kinase family, that have been implicated in a number of cancers. This manuscript describes the design, synthesis and SAR of covalent CDK14 inhibitors, culminating in identification of FMF-04-159-2, a potent, covalent CDK14 inhibitor with a TAIRE kinase biased selectivity profile.
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PMID:Synthesis and structure activity relationships of a series of 4-amino-1H-pyrazoles as covalent inhibitors of CDK14. 3117 10


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