Modulating target engagement of small molecules via drug delivery: approaches and applications in drug discovery and development

2020 ◽  
Author(s):  
Wenzhan Yang ◽  
Shobha N. Bhattachar ◽  
Phenil J. Patel ◽  
Margaret Landis ◽  
Dipal Patel ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Discovery ◽  
Small Molecules ◽  
Target Engagement ◽  
Drug Discovery And Development

scholarly journals Nuclear Magnetic Resonance Spectroscopyan Evolutionary Approach to Drug Design

2007 ◽  
Vol 4 (3) ◽  
pp. 294-301
Author(s):  
Neeraj Upmanyu ◽  
Gopal Garg ◽  
Archana Dolly ◽  
Pradeep Mishra
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Drug Discovery ◽  
Magnetic Resonance ◽  
Drug Design ◽  
Small Molecules ◽  
Pharmaceutical Research ◽  
Three Dimensional ◽  
Drug Discovery And Development ◽  
4D Nmr ◽  
Nuclear Magnetic

Ever since Nuclear Magnetic Resonance (NMR) spectroscopy hit the analytical scene; its capabilities and applications continue to evolve. Originally designed as a way to verify the structure of relatively small compounds, the technology of NMR has exploded and become a valuable means for studying protein structure. NMR has proved to be a valuable tool in pharmaceutical research, as it has entered new arena of drug discovery and structural genomics. NMR can provide information on the three-dimensional structures of small molecules in solution, high-molecular-weight complexes, and the details of enzyme mechanisms that can be used to aid in drug design. In the present scenario, the availability of high magnetic fields; improved software, high resolution probes, and electronics; more versatile pulse programmers; and most importantly the development of 2D, 3D and 4D NMR, have revolutionized the field of drug discovery and development.

scholarly journals MM-PBSA and the Importance of the Dielectric Constant for Kinase Drug Design

2020 ◽  
Author(s):  
Melanie Schneider ◽  
Gilles Labesse
Keyword(s):  
Dielectric Constant ◽  
Drug Discovery ◽  
Drug Design ◽  
Small Molecules ◽  
Design Process ◽  
Critical Role ◽  
Binding Pocket ◽  
Solvation Energy ◽  
Drug Discovery And Development ◽  
The Common

Predicting the interactions between a set of small molecules and its target plays a critical role in drug discovery and development. Especially in later stages of the drug design process, when a reduced set of molecules is in focus, reliable and accurate binding affinity estimations are important for targeted modifications of given lead molecules.<div><div>Current limitations in affinity prediction originate from the lack of accurate estimates for solvation energy and entropy. MM-PBSA and the related MM-GBSA aim at providing better estimates.</div><div>From our studies we infer that the common approach using one dielectric constant for the binding pocket may be misleading (here in the case of a kinase), especially when designed ligands/drugs contain charges. Thus, a range of selected values for the solute dielectric constant is preferred for better and more reliable comparisons.</div></div>

scholarly journals Zebrafish as a model system for biomedical studies

2010 ◽  
Vol 56 (1) ◽  
pp. 120-131 ◽  
Author(s):  
N.F. Belyaeva ◽  
V.N. Kashirtseva ◽  
N.V. Medvedeva ◽  
Yu.Yu. Khudoklinova ◽  
O.M. Ipatova ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Developmental Disorders ◽  
Model Organism ◽  
Toxicity Testing ◽  
New Drugs ◽  
Human Diseases ◽  
Research Model ◽  
Drug Discovery And Development ◽  
Phospholipid Nanoparticles

Zebrafish (Danio rerio) are now firmly established as a powerful research model for many areas of biology and medicine. Here, we review some achievements of zebrafish - based assays for modeling human diseases and for drug discovery and development. For drug discovery, zebrafish are especially valuable in the earlier stages of research as they provide a model organism to demonstrate a new treatment's efficacy and toxicity before more costly mammalian models are used. This review provides examples of compounds known to be toxic to humans that have been demonstrated to functional similarly in zebrafish. Major advantages of zebrafish embryons are that they are readily permeable to small molecules added to their incubation medium and the transparent chorion enables the easy observation of development. Assay of acute toxicity (LC50 estimation) in embryos can also include the screening for developmental disorders as an indicator of teratogenic effects. We used zebrafish for toxicity testing of new drugs on the base of phospholipid nanoparticles. The organization of the genome and the pathways controlling signal transduction appear to be highly conserved between zebrafish and humans that allow using zebrafish for modeling of human diseases some examples of which are illustrated in this paper.

scholarly journals MM-PBSA and the Importance of the Dielectric Constant for Kinase Drug Design

2020 ◽  
Author(s):  
Melanie Schneider ◽  
Gilles Labesse
Keyword(s):  
Dielectric Constant ◽  
Drug Discovery ◽  
Drug Design ◽  
Small Molecules ◽  
Design Process ◽  
Critical Role ◽  
Binding Pocket ◽  
Solvation Energy ◽  
Drug Discovery And Development ◽  
The Common

Predicting the interactions between a set of small molecules and its target plays a critical role in drug discovery and development. Especially in later stages of the drug design process, when a reduced set of molecules is in focus, reliable and accurate binding affinity estimations are important for targeted modifications of given lead molecules.<div><div>Current limitations in affinity prediction originate from the lack of accurate estimates for solvation energy and entropy. MM-PBSA and the related MM-GBSA aim at providing better estimates.</div><div>From our studies we infer that the common approach using one dielectric constant for the binding pocket may be misleading (here in the case of a kinase), especially when designed ligands/drugs contain charges. Thus, a range of selected values for the solute dielectric constant is preferred for better and more reliable comparisons.</div></div>

scholarly journals Small molecule recognition of disease-relevant RNA structures

2020 ◽  
Vol 49 (19) ◽  
pp. 7167-7199 ◽  
Author(s):  
Samantha M. Meyer ◽  
Christopher C. Williams ◽  
Yoshihiro Akahori ◽  
Toru Tanaka ◽  
Haruo Aikawa ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Small Molecule ◽  
Rna Structures ◽  
Drug Discovery And Development ◽  
New Frontier ◽  
Molecule Recognition

Targeting RNAs with small molecules, a new frontier in drug discovery and development.

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