scholarly journals Stem cells in natural product and medicinal plant drug discovery—An overview of new screening approaches

2020 ◽  
Vol 131 ◽  
pp. 110730
Author(s):  
Erastus Nembu Nembo ◽  
Jürgen Hescheler ◽  
Filomain Nguemo
Author(s):  
Mai Luo ◽  
Jessica N. Spradlin ◽  
Scott M. Brittain ◽  
Jeffery M. McKenna ◽  
John A. Tallarico ◽  
...  

AbstractThe translation of natural product function to fully synthetic small molecules has remained an important process in medicinal chemistry for decades resulting in numerous FDA-approved medicines. We recently discovered that the terpene natural product nimbolide can be utilized as a covalent recruiter of the E3 ubiquitin ligase RNF114 for use in targeted protein degradation (TPD) – a powerful therapeutic modality within modern day drug discovery. Using activity-based protein profiling-enabled covalent ligand screening approaches, we herein report the discovery of fully synthetic RNF114-based recruiter molecules that can also be exploited for PROTAC applications, and demonstrate their utility in degrading therapeutically relevant targets such as BRD4 and BCR-ABL in cells. The identification of simple and easily manipulated drug-like scaffolds that can mimic the function of a complex natural product is beneficial in further expanding the toolbox of E3 ligase recruiters, an area of great importance in drug discovery and chemical biology.


2020 ◽  
Vol 21 (10) ◽  
pp. 751-767
Author(s):  
Pobitra Borah ◽  
Sangeeta Hazarika ◽  
Satyendra Deka ◽  
Katharigatta N. Venugopala ◽  
Anroop B. Nair ◽  
...  

The successful conversion of natural products (NPs) into lead compounds and novel pharmacophores has emboldened the researchers to harness the drug discovery process with a lot more enthusiasm. However, forfeit of bioactive NPs resulting from an overabundance of metabolites and their wide dynamic range have created the bottleneck in NP researches. Similarly, the existence of multidimensional challenges, including the evaluation of pharmacokinetics, pharmacodynamics, and safety parameters, has been a concerning issue. Advancement of technology has brought the evolution of traditional natural product researches into the computer-based assessment exhibiting pretentious remarks about their efficiency in drug discovery. The early attention to the quality of the NPs may reduce the attrition rate of drug candidates by parallel assessment of ADMET profiling. This article reviews the status, challenges, opportunities, and integration of advanced technologies in natural product research. Indeed, emphasis will be laid on the current and futuristic direction towards the application of newer technologies in early-stage ADMET profiling of bioactive moieties from the natural sources. It can be expected that combinatorial approaches in ADMET profiling will fortify the natural product-based drug discovery in the near future.


2016 ◽  
Vol 17 (2) ◽  
pp. 256 ◽  
Author(s):  
Mohammed Kawser Hossain ◽  
Ahmed Abdal Dayem ◽  
Jihae Han ◽  
Subbroto Kumar Saha ◽  
Gwang-Mo Yang ◽  
...  

2010 ◽  
Vol 51 (1) ◽  
pp. 171-180 ◽  
Author(s):  
George E. Chlipala ◽  
Aleksej Krunic ◽  
Shunyan Mo ◽  
Megan Sturdy ◽  
Jimmy Orjala

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