Recent Update on Targeting <i>c-MYC</i> G-Quadruplexes by Small Molecules for Anticancer Therapeutics

Chaudhuri, Ritapa; Bhattacharya, S.; Dash, Jyotirmayee; Bhattacharya, Santanu

doi:10.1021/acs.jmedchem.0c01145

Cited by 76 publications

(73 citation statements)

References 185 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, the transcriptional activity of an ample number of cancer-associated genes has been reported to be amenable of G4-mediated regulation [ 2 , 14 , 15 , 17 ]. The finding that the expression of the proto-oncogene MYC (V-myc avian myelocytomatosis viral oncogene homolog) may undergo a G4-mediated regulation has been paradigmatic and has furnished the proof-of-concept for the G4-dependent regulation of gene expression [ 57 , 58 ].…”

Section: Targeting G-quadruplex Structures In Cancermentioning

confidence: 99%

On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

Alessandrini

Recagni

Zaffaroni

et al. 2021

IJMS

View full text Add to dashboard Cite

Nucleic acid sequences able to adopt a G-quadruplex conformation are overrepresented within the human genome. This evidence strongly suggests that these genomic regions have been evolutionary selected to play a pivotal role in several aspects of cell biology. In the present review article, we provide an overview on the biological impact of targeting G-quadruplexes in cancer. A variety of small molecules showing good G-quadruplex stabilizing properties has been reported to exert an antitumor activity in several preclinical models of human cancers. Moreover, promiscuous binders and multiple targeting G-quadruplex ligands, cancer cell defense responses and synthetic lethal interactions of G-quadruplex targeting have been also highlighted. Overall, evidence gathered thus far indicates that targeting G-quadruplex may represent an innovative and fascinating therapeutic approach for cancer. The continued methodological improvements, the development of specific tools and a careful consideration of the experimental settings in living systems will be useful to deepen our knowledge of G-quadruplex biology in cancer, to better define their role as therapeutic targets and to help design and develop novel and reliable G-quadruplex-based anticancer strategies.

show abstract

Section: Targeting G-quadruplex Structures In Cancermentioning

confidence: 99%

On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

Alessandrini

Recagni

Zaffaroni

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Indeed, contemporary research has demonstrated the importance of G4s in various cellular processes, including interactions with TFs [60][61][62][63]. Moreover, the targeting of the unique structure of G4s is proposed as a good tool for various diseases therapies including cancer [64][65][66][67][68].…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay

Monti

Brázda

Bohálová

et al. 2021

Genes

View full text Add to dashboard Cite

P53, P63, and P73 proteins belong to the P53 family of transcription factors, sharing a common gene organization that, from the P1 and P2 promoters, produces two groups of mRNAs encoding proteins with different N-terminal regions; moreover, alternative splicing events at C-terminus further contribute to the generation of multiple isoforms. P53 family proteins can influence a plethora of cellular pathways mainly through the direct binding to specific DNA sequences known as response elements (REs), and the transactivation of the corresponding target genes. However, the transcriptional activation by P53 family members can be regulated at multiple levels, including the DNA topology at responsive promoters. Here, by using a yeast-based functional assay, we evaluated the influence that a G-quadruplex (G4) prone sequence adjacent to the p53 RE derived from the apoptotic PUMA target gene can exert on the transactivation potential of full-length and N-terminal truncated P53 family α isoforms (wild-type and mutant). Our results show that the presence of a G4 prone sequence upstream or downstream of the P53 RE leads to significant changes in the relative activity of P53 family proteins, emphasizing the potential role of structural DNA features as modifiers of P53 family functions at target promoter sites.

show abstract

“…Indeed, these intrinsically stable folds can be further stabilised by chemicals, including PDS, PhenDC3 ( Figure 4 ), and other structurally related and unrelated compounds (reviewed in ref. [ 203 ]). Such GQ stabilisers are currently under focus for their potential use as anticancer drugs.…”

Section: Targeting the Viral Rnamentioning

confidence: 99%

Rhinovirus Inhibitors: Including a New Target, the Viral RNA

Real-Hohn

Blaas

2021

Viruses

View full text Add to dashboard Cite

Rhinoviruses (RVs) are the main cause of recurrent infections with rather mild symptoms characteristic of the common cold. Nevertheless, RVs give rise to enormous numbers of absences from work and school and may become life-threatening in particular settings. Vaccination is jeopardised by the large number of serotypes eliciting only poorly cross-neutralising antibodies. Conversely, antivirals developed over the years failed FDA approval because of a low efficacy and/or side effects. RV species A, B, and C are now included in the fifteen species of the genus Enteroviruses based upon the high similarity of their genome sequences. As a result of their comparably low pathogenicity, RVs have become a handy model for other, more dangerous members of this genus, e.g., poliovirus and enterovirus 71. We provide a short overview of viral proteins that are considered potential drug targets and their corresponding drug candidates. We briefly mention more recently identified cellular enzymes whose inhibition impacts on RVs and comment novel approaches to interfere with infection via aggregation, virus trapping, or preventing viral access to the cell receptor. Finally, we devote a large part of this article to adding the viral RNA genome to the list of potential drug targets by dwelling on its structure, folding, and the still debated way of its exit from the capsid. Finally, we discuss the recent finding that G‑quadruplex stabilising compounds impact on RNA egress possibly via obfuscating the unravelling of stable secondary structural elements.

show abstract

Recent Update on Targeting c-MYC G-Quadruplexes by Small Molecules for Anticancer Therapeutics

Cited by 76 publications

References 185 publications

On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay

Rhinovirus Inhibitors: Including a New Target, the Viral RNA

Contact Info

Product

Resources

About