scholarly journals Chemical Screening Approaches Enabling Drug Discovery of Autophagy Modulators for Biomedical Applications in Human Diseases

2019 ◽  
Vol 7 ◽  
Author(s):  
Prashanta Kumar Panda ◽  
Alexandra Fahrner ◽  
Somya Vats ◽  
Elena Seranova ◽  
Vartika Sharma ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Biomedical Applications ◽  
Human Diseases ◽  
Chemical Screening ◽  
Screening Approaches

scholarly journals Druggable Transient Pockets in Protein Kinases

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 651
Author(s):  
Koji Umezawa ◽  
Isao Kii
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Protein Kinases ◽  
Binding Sites ◽  
Kinase Inhibitors ◽  
Screening Methods ◽  
Research Attention ◽  
Folding Process ◽  
Chemical Screening ◽  
Inhibitory Mechanisms

Drug discovery using small molecule inhibitors is reaching a stalemate due to low selectivity, adverse off-target effects and inevitable failures in clinical trials. Conventional chemical screening methods may miss potent small molecules because of their use of simple but outdated kits composed of recombinant enzyme proteins. Non-canonical inhibitors targeting a hidden pocket in a protein have received considerable research attention. Kii and colleagues identified an inhibitor targeting a transient pocket in the kinase DYRK1A during its folding process and termed it FINDY. FINDY exhibits a unique inhibitory profile; that is, FINDY does not inhibit the fully folded form of DYRK1A, indicating that the FINDY-binding pocket is hidden in the folded form. This intriguing pocket opens during the folding process and then closes upon completion of folding. In this review, we discuss previously established kinase inhibitors and their inhibitory mechanisms in comparison with FINDY. We also compare the inhibitory mechanisms with the growing concept of “cryptic inhibitor-binding sites.” These sites are buried on the inhibitor-unbound surface but become apparent when the inhibitor is bound. In addition, an alternative method based on cell-free protein synthesis of protein kinases may allow the discovery of small molecules that occupy these mysterious binding sites. Transitional folding intermediates would become alternative targets in drug discovery, enabling the efficient development of potent kinase inhibitors.

Recent Advances on Small Molecule Medicinal Chemistry to Treat Human Diseases-Part III

2021 ◽  
Vol 21 (17) ◽  
pp. 1517-1518
Author(s):  
Dharmendra Kumar Yadav
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Small Molecule ◽  
Anticancer Agents ◽  
Medicinal Chemistry ◽  
Review Article ◽  
Human Diseases ◽  
Bioactive Metabolite ◽  
Metabolite Production ◽  
Life Threatening

The discovery and utilization of novel metabolites from natural sources are gaining momentum in the present era. The drug discovery programs have witnessed a remarkable shift from conventional medicines to exploiting natural products and their “value addition”, for treating lifethreatening diseases. The global outbreak of life-threatening diseases namely Ebola, SARS,including infections of the bloodstream (bacteremia), heart valves (endocarditis), lungs (pneumonia), and brain (meningitis) and AIDS calls for a more targeted approach to effectively combat the emerging diseases. In the present scenario, natural products and their extracts are being explored extensively for the treatment of various life threatening diseases. In this thematic issue, several review articles contributed by the scientist and researchers in the different areas of medicinal chemistry, synthetic chemistry, new emerging multi-drug targets were collected. This issue begins with a review article on the “Chemistry and Pharmacology of Natural Catechins from Camellia sinensis as anti-MRSA agents” by Gaur et al. and focuses on the spread of MRSA strains is of great concern because of limited treatment options for staphylococcal infections, since these strains are resistant to the entire class of β-lactam antibiotics. In addition, MRSA exhibits resistance to other classes of antimicrobial agents such as fluoroquinolones, cephalosporins, aminoglycosides, macrolide and even glycopeptides (vancomycin and teicoplanine), leading to the emergence of resistant strains such as glycopeptide intermediate (GISA) and resistant strain (GRSA) of S. aureus. In this review, chemical constituents responsible for the anti-MRSA activity of tea are explored [1]. The next article of this issue is a review article on the “Recent Advancements in the Synthesis and Chemistry of Benzofused Nitrogen- and Oxygen-based Bioactive Heterocycles” by Sharma et al. which focuses on medicinal importance of these bioactive benzo-fused heterocycles; special attention has been given to their synthesis as well as medicinal/pharmaceutical properties in detail [2]. “Trends in pharmaceutical design of Endophytes as anti-infective,” by Tiwari et al., is the third article in this issue. The review focused on the meta-analysis of bioactive metabolite production from endophytes, extensively discussing the bioprospection of natural products for pharmaceutical applications. In light of the emerging importance of endophytes as antiinfective agents, an exploration of the pharmaceutical design of novel chemical entities and analogues has enabled efficient and cost-effective drug discovery programs. However, bottlenecks in endophytic biology and research requires a better understanding of endophytic dynamics and mechanism of bioactive metabolite production towards a sustainable drug discovery program [3]. The last article of this issue is also research article on “Recent development of tetrahydro-quinoline/isoquinoline based compounds as anticancer agents” by Yadav et al. The article reported the synthesis of potent tetrahydroquinoline/isoquinoline molecules of the last 10 years with their anticancer properties in various cancer cell lines and stated their half-maximal inhibitory concentration (IC50). In addition, we also considered the discussion of molecular docking and structural activity relationship wherever provided to understand the possible mode of activity an target involved and structural features responsible for the better activity, so the reader can directly find detail for designing new anticancer agents. [4]. Finally I would like to thank all authors who contributed to this issue, titled “Recent advances on small molecule medicinal chemistry to treat human diseases”.

scholarly journals Identification of IAA Transport Inhibitors Including Compounds Affecting Cellular PIN Trafficking by Two Chemical Screening Approaches Using Maize Coleoptile Systems

2012 ◽  
Vol 53 (10) ◽  
pp. 1671-1682 ◽  
Author(s):  
Takeshi Nishimura ◽  
Naoyuki Matano ◽  
Taichi Morishima ◽  
Chieko Kakinuma ◽  
Ken-ichiro Hayashi ◽  
...  
Keyword(s):  
Chemical Screening ◽  
Maize Coleoptile ◽  
Transport Inhibitors ◽  
Screening Approaches

Novel screening approaches for human prion diseases drug discovery

2019 ◽  
Vol 14 (10) ◽  
pp. 983-993
Author(s):  
Fabio Moda ◽  
Maria Laura Bolognesi ◽  
Giuseppe Legname
Keyword(s):  
Drug Discovery ◽  
Prion Diseases ◽  
Screening Approaches

Epigenetics—an emerging and highly promising source of new drug targets

MedChemComm ◽  
2012 ◽  
Vol 3 (2) ◽  
pp. 162-166 ◽  
Author(s):  
Nessa Carey
Keyword(s):  
Gene Expression ◽  
Drug Discovery ◽  
Drug Targets ◽  
Epigenetic Modifications ◽  
Regulatory Process ◽  
Human Diseases ◽  
Histone Proteins ◽  
New Drug ◽  
Promising Source

Epigenetic modifications to DNA and its associated histone proteins are major influences on gene expression. This regulatory process is disrupted in cancer and a range of chronic human diseases, and provides attractive new intervention points and targets for drug discovery.

Drug discovery and development for spinal muscular atrophy: lessons from screening approaches and future challenges for clinical development

2010 ◽  
Vol 2 (9) ◽  
pp. 1429-1440 ◽  
Author(s):  
Rebecca M Pruss ◽  
Marc Giraudon-Paoli ◽  
Svetlana Morozova ◽  
Patrick Berna ◽  
Jean-Louis Abitbol ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Clinical Development ◽  
Drug Discovery And Development ◽  
Future Challenges ◽  
Screening Approaches
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