Dual-target inhibitors based on BRD4: Novel therapeutic approaches for cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Sitao Zhang ◽  
Yanzhao Chen ◽  
Chengsen Tian ◽  
Yujing He ◽  
Zeru Tian ◽  
...  
Keyword(s):  
Regulatory Elements ◽  
Therapeutic Approaches ◽  
Cellular Processes ◽  
Improve Treatment ◽  
Dual Targeting ◽  
Structure Activity ◽  
Dual Inhibitors ◽  
Insight Into ◽  
Dual Target ◽  
Improve Treatment Efficacy

: Bromodomain and Extraterminal domain (BET) proteins are a family of important proteins to build transcriptionpromoting complexes by reading acetylated chromatin status and accumulating on transcriptionally active regulatory elements. BRD4 as an important member of BET family proteins can assist the expression of various well-known oncogenes, indicating that inhibiting BRD4 is an effective strategy for cancer treatment. In view of the fact that BRD4 inhibitor and inhibitors of some enzymatic/non-enzymatic proteins share many common targets and do similar effects on cellular processes, combined inhibition of BRD4 and these proteins is regarded as a rational strategy to improve treatment efficacy. In this review, we summarize the molecular interplay between BRD4 and other proteins. Moreover, we summarize the corresponding dual targeting inhibitors, for example HDAC/BRD4 dual inhibitors, PLK1/BRD4 dual inhibitors, PI3K/BRD4 dual inhibitors and so on, in cancer therapy and we make an insight into the structure-activity relationships of these dual-target agents.

Multi-Targeting Anticancer Agents: Rational Approaches, Synthetic Routes and Structure Activity Relationship

2019 ◽  
Vol 19 (7) ◽  
pp. 842-874 ◽  
Author(s):  
Harbinder Singh ◽  
Nihar Kinarivala ◽  
Sahil Sharma
Keyword(s):  
Anticancer Agents ◽  
Cancer Drug ◽  
Design And Synthesis ◽  
Cancer Drug Discovery ◽  
Dual Targeting ◽  
Structure Activity ◽  
Anti Cancer ◽  
Dual Inhibitors ◽  
Recent Trends ◽  
Synthetic Routes

We live in a world with complex diseases such as cancer which cannot be cured with one-compound one-target based therapeutic paradigm. This could be due to the involvement of multiple pathogenic mechanisms. One-compound-various-targets stratagem has become a prevailing research topic in anti-cancer drug discovery. The simultaneous interruption of two or more targets has improved the therapeutic efficacy as compared to the specific targeted based therapy. In this review, six types of dual targeting agents along with some interesting strategies used for their design and synthesis are discussed. Their pharmacology with various types of the molecular interactions within their specific targets has also been described. This assemblage will reveal the recent trends and insights in front of the scientific community working in dual inhibitors and help them in designing the next generation of multi-targeted anti-cancer agents.

scholarly journals HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3575
Author(s):  
Dimitris Karagiannis ◽  
Theodoros Rampias
Keyword(s):  
Tumor Heterogeneity ◽  
Histone Deacetylase Inhibitors ◽  
Phenotypic Variability ◽  
Hdac Inhibitors ◽  
Cancer Therapeutics ◽  
Mechanisms Of Action ◽  
Therapeutic Approaches ◽  
Cellular Processes ◽  
Environmental Selection ◽  
Stochastic Events

Intra-tumoral heterogeneity presents a major obstacle to cancer therapeutics, including conventional chemotherapy, immunotherapy, and targeted therapies. Stochastic events such as mutations, chromosomal aberrations, and epigenetic dysregulation, as well as micro-environmental selection pressures related to nutrient and oxygen availability, immune infiltration, and immunoediting processes can drive immense phenotypic variability in tumor cells. Here, we discuss how histone deacetylase inhibitors, a prominent class of epigenetic drugs, can be leveraged to counter tumor heterogeneity. We examine their effects on cellular processes that contribute to heterogeneity and provide insights on their mechanisms of action that could assist in the development of future therapeutic approaches.

scholarly journals Effects of Glucosinolate-Derived Isothiocyanates on Fungi: A Comprehensive Review on Direct Effects, Mechanisms, Structure-Activity Relationship Data and Possible Agricultural Applications

2021 ◽  
Vol 7 (7) ◽  
pp. 539
Author(s):  
Tamás Plaszkó ◽  
Zsolt Szűcs ◽  
Gábor Vasas ◽  
Sándor Gonda
Keyword(s):  
Mycorrhizal Fungi ◽  
Current Knowledge ◽  
Synergistic Activity ◽  
Microbial Composition ◽  
Soil Microbial ◽  
Structure Activity ◽  
Agricultural Applications ◽  
Antifungal Action ◽  
Insight Into ◽  
Soil Microbial Composition

Plants heavily rely on chemical defense systems against a variety of stressors. The glucosinolates in the Brassicaceae and some allies are the core molecules of one of the most researched such pathways. These natural products are enzymatically converted into isothiocyanates (ITCs) and occasionally other defensive volatile organic constituents (VOCs) upon fungal challenge or tissue disruption to protect the host against the stressor. The current review provides a comprehensive insight on the effects of the isothiocyanates on fungi, including, but not limited to mycorrhizal fungi and pathogens of Brassicaceae. In the review, our current knowledge on the following topics are summarized: direct antifungal activity and the proposed mechanisms of antifungal action, QSAR (quantitative structure-activity relationships), synergistic activity of ITCs with other agents, effects of ITCs on soil microbial composition and allelopathic activity. A detailed insight into the possible applications is also provided: the literature of biofumigation studies, inhibition of post-harvest pathogenesis and protection of various products including grains and fruits is also reviewed herein.

scholarly journals Considerations when investigating lncRNA function in vivo

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Andrew R Bassett ◽  
Asifa Akhtar ◽  
Denise P Barlow ◽  
Adrian P Bird ◽  
Neil Brockdorff ◽  
...  
Keyword(s):  
Normal Cell ◽  
Regulatory Elements ◽  
Genomic Locus ◽  
Cellular Processes ◽  
Cell Processes ◽  
Non Coding Rnas ◽  
Per Se ◽  
Dna Regulatory Elements

Although a small number of the vast array of animal long non-coding RNAs (lncRNAs) have known effects on cellular processes examined in vitro, the extent of their contributions to normal cell processes throughout development, differentiation and disease for the most part remains less clear. Phenotypes arising from deletion of an entire genomic locus cannot be unequivocally attributed either to the loss of the lncRNA per se or to the associated loss of other overlapping DNA regulatory elements. The distinction between cis- or trans-effects is also often problematic. We discuss the advantages and challenges associated with the current techniques for studying the in vivo function of lncRNAs in the light of different models of lncRNA molecular mechanism, and reflect on the design of experiments to mutate lncRNA loci. These considerations should assist in the further investigation of these transcriptional products of the genome.

Pyridine moiety: An insight into recent advances in treatment of cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Rakesh Sahu ◽  
Rakhi Mishra ◽  
Rajnish Kumar ◽  
Salahuddin ◽  
Chandana Majee ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Antitumor Agents ◽  
Pyridine Moiety ◽  
Structure Activity ◽  
Wide Range ◽  
Global Health Issue ◽  
Effective Drugs ◽  
Published Research ◽  
Insight Into

: The incidence of cancer is increasing worldwide, affecting a vast majority of the human population. As new different anticancer agents are being developed now, the requirement is to deal somehow with them and evaluate their safety. Among them, pyridine based drugs are contributing a lot, as it is one of the imperative pharmacophores occurring synthetically as well as naturally in heterocyclic compounds, and having a wide range of therapeutic applications in the area of drug discovery, thereby offering many chances for further improvement in antitumor agents via acting onto numerous receptors of extreme prominence. Many pyridine derivatives have been reported to inhibit enzymes, receptors and many other targets for controlling and curing the global health issue of cancer. Nowadays, in combination with other moieties, researchers are focusing on the development of pyridine-based new derivatives for cancer treatment. Therefore, this review sheds light on the recent therapeutic expansions of pyridine together with its molecular docking, structure-activity-relationship, availability in the market, and a summary of recently patented and published research works that shall jointly help the scientists to produce effective drugs with the desired pharmacological activity.

Special Issue on "Immunomodulatory and therapeutic approaches against infectious diseases"

2011 ◽  
Vol 1 (5) ◽  
pp. 1-2
Author(s):  
Lavkush Dwivedi
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Human Health ◽  
Immune Stimulation ◽  
Defense System ◽  
Special Issue ◽  
Therapeutic Approaches ◽  
Major Constraint ◽  
The World ◽  
Insight Into

Infectious diseases and consequent immune imbalancesare major constraint in human health managementthroughout the world. However, in recentdecades enormous efforts have been made to elucidatethe immunomodulatory approaches againstinfectious diseases. Immunomodulation is a therapeuticapproach in which we try to intervene inauto regulating processes of the defense system toadjust the immune response at a desired level.The present special issue on cutting edge issues inImmunomodulation like Immune stimulation, Immunesuppression, Immune potentiating and immunereinforcement summarizes our current understandingof this complex mosaic. The accompanyingselection of recent articles from across theworld provides further insight into this topic. 

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