Drug Discovery: Small Molecule Drugs

Drugs ◽  
2005 ◽  
pp. 43-74
Keyword(s):  
Drug Discovery ◽  
Small Molecule ◽  
Small Molecule Drugs

meta-Non-flat substituents: a novel molecular design to improve aqueous solubility in small molecule drug discovery

2021 ◽  
Author(s):  
Yuki Ichikawa ◽  
Michiaki Hiramatsu ◽  
Yusuke Mita ◽  
Makoto Makishima ◽  
Yotaro Matsumoto ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Small Molecule ◽  
Molecular Design ◽  
Aqueous Solubility ◽  
Small Molecule Drug ◽  
Small Molecule Drugs

We found a novel molecular design for improvement in the aqueous solubility of small molecule drugs.

scholarly journals Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery

2020 ◽  
Vol 21 (15) ◽  
pp. 5262 ◽  
Author(s):  
Qingxin Li ◽  
CongBao Kang
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Structural Biology ◽  
Small Molecule ◽  
Molecular Interactions ◽  
Mechanisms Of Action ◽  
Rational Drug Design ◽  
Binding Modes ◽  
Small Molecule Drugs ◽  
Rational Drug

Small-molecule drugs are organic compounds affecting molecular pathways by targeting important proteins. These compounds have a low molecular weight, making them penetrate cells easily. Small-molecule drugs can be developed from leads derived from rational drug design or isolated from natural resources. A target-based drug discovery project usually includes target identification, target validation, hit identification, hit to lead and lead optimization. Understanding molecular interactions between small molecules and their targets is critical in drug discovery. Although many biophysical and biochemical methods are able to elucidate molecular interactions of small molecules with their targets, structural biology is the most powerful tool to determine the mechanisms of action for both targets and the developed compounds. Herein, we reviewed the application of structural biology to investigate binding modes of orthosteric and allosteric inhibitors. It is exemplified that structural biology provides a clear view of the binding modes of protease inhibitors and phosphatase inhibitors. We also demonstrate that structural biology provides insights into the function of a target and identifies a druggable site for rational drug design.

Application of Biological Target Fishing Technology in Drug Discovery

2020 ◽  
Vol 980 ◽  
pp. 210-219
Author(s):  
Xian Zhi Ye
Keyword(s):  
Drug Discovery ◽  
Small Molecule ◽  
Drug Targets ◽  
Surface Plasma Resonance ◽  
Practical Applications ◽  
Small Molecule Drug ◽  
New Methods ◽  
Small Molecule Drugs ◽  
Biological Target ◽  
Target Fishing

Target fishing, a cutting-edge technology for drug research and development, plays a significant role in drug discovery. Varieties of methods for finding small-molecule drug targets have come into being driven by genomics, proteomics, bioinformatics and other technologies. These new methods are mainly based on the expression of gene or protein and proteins properties, including affinity and stability and so on. A serious challenge for the most widely used small molecule drugs is the discovery and identification of biological (and potential therapeutic) targets. Herein, we enumerate five biological target fishing techniques, including surface plasma resonance (SPR) techniques, random photo modified probes, drug affinity responsive target stability, fishing-rod strategy, and photo affinity labeling. And then we introduces the principles of operation, practical applications in the biological field of five methods, and analysis of their shortcomings.

Quantitative Ranking of Ligand Binding Kinetics with a Multiscale Milestoning Simulation Approach

2018 ◽  
Author(s):  
Benjamin R. Jagger ◽  
Christoper T. Lee ◽  
Rommie Amaro
Keyword(s):  
Molecular Dynamics ◽  
Drug Discovery ◽  
Small Molecule ◽  
Brownian Dynamics ◽  
Model Simulation ◽  
Computational Cost ◽  
Lead Selection ◽  
Delta G ◽  
Dynamics Simulations

<p>The ranking of small molecule binders by their kinetic (kon and koff) and thermodynamic (delta G) properties can be a valuable metric for lead selection and optimization in a drug discovery campaign, as these quantities are often indicators of in vivo efficacy. Efficient and accurate predictions of these quantities can aid the in drug discovery effort, acting as a screening step. We have previously described a hybrid molecular dynamics, Brownian dynamics, and milestoning model, Simulation Enabled Estimation of Kinetic Rates (SEEKR), that can predict kon’s, koff’s, and G’s. Here we demonstrate the effectiveness of this approach for ranking a series of seven small molecule compounds for the model system, -cyclodextrin, based on predicted kon’s and koff’s. We compare our results using SEEKR to experimentally determined rates as well as rates calculated using long-timescale molecular dynamics simulations and show that SEEKR can effectively rank the compounds by koff and G with reduced computational cost. We also provide a discussion of convergence properties and sensitivities of calculations with SEEKR to establish “best practices” for its future use.</p>

Growing by Sharing - Story of Ryvu and Selvita

2020 ◽  
Vol 7 (1) ◽  
pp. 33-47
Author(s):  
Magdalena Marciniak
Keyword(s):  
Drug Discovery ◽  
Business Model ◽  
Small Molecule ◽  
Contract Research ◽  
Industrial Enterprises ◽  
Strong Position ◽  
Small Molecule Therapeutics

Ryvu Therapeutics and Selvita originated in 2007, a time when drug discovery in Poland was still not pursued by industrial enterprises. For many years, both entities operated one company and were known under a common name Selvita S.A., combining their efforts on both innovative small-molecule therapeutics for oncology and expertise in Contract Research Services (CRO). Following more than a decade of such a hybrid business model, Selvita established a strong position in the field of drug discovery and built trust among partners, clients, and investors globally. This encouraged the leaders of the company to separate the two divisions into fully autonomous units, which in fact, had already been operating quite independently and both were successful in diverse areas of drug discovery activities. At the beginning of October 2019, two new companies were established and both parts were given independence and more opportunities for growth. Discovery and development engine was named as Ryvu Therapeutics, and the CRO part of the company remained with the name Selvita. To reach this stage, both the divisions went through an interesting journey together, supporting and strengthening each other for the benefit of both.

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