scholarly journals Modular Approaches to Synthesize Activity- and Affinity-Based Chemical Probes

2021 ◽  
Vol 9 ◽  
Author(s):  
Antonie J. van der Zouwen ◽  
Martin D. Witte
Keyword(s):  
Small Molecule ◽  
Multicomponent Reactions ◽  
Chemical Probes ◽  
Protein Activity ◽  
Phage Displays ◽  
The Past ◽  
New Drug ◽  
Small Molecule Modulators

Combinatorial and modular methods to synthesize small molecule modulators of protein activity have proven to be powerful tools in the development of new drug-like molecules. Over the past decade, these methodologies have been adapted toward utilization in the development of activity- and affinity-based chemical probes, as well as in chemoproteomic profiling. In this review, we will discuss how methods like multicomponent reactions, DNA-encoded libraries, phage displays, and others provide new ways to rapidly screen novel chemical probes against proteins of interest.

scholarly journals Boltzmann Docking Identifies Allosteric Small Molecule Modulators of Protein Activity

2018 ◽  
Vol 114 (3) ◽  
pp. 58a
Author(s):  
Thomas E. Frederick ◽  
Kathryn M. Hart ◽  
Katelyn E. Moeder ◽  
Chris M.W. Ho ◽  
Maxwell I. Zimmerman ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Activity ◽  
Small Molecule Modulators

scholarly journals Perspectives on the Discovery of Small-Molecule Modulators for Epigenetic Processes

2012 ◽  
Vol 17 (5) ◽  
pp. 555-571 ◽  
Author(s):  
Quinn Lu ◽  
Amy M. Quinn ◽  
Mehul P. Patel ◽  
Simon F. Semus ◽  
Alan P. Graves ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Small Molecule ◽  
Intervention Strategies ◽  
Mechanistic Studies ◽  
Chemical Probes ◽  
Epigenetic Gene Regulation ◽  
Small Molecule Modulators ◽  
Hit Identification ◽  
Critical Process ◽  
Epigenetic Processes

Epigenetic gene regulation is a critical process controlling differentiation and development, the malfunction of which may underpin a variety of diseases. In this article, we review the current landscape of small-molecule epigenetic modulators including drugs on the market, key compounds in clinical trials, and chemical probes being used in epigenetic mechanistic studies. Hit identification strategies for the discovery of small-molecule epigenetic modulators are summarized with respect to writers, erasers, and readers of histone marks. Perspectives are provided on opportunities for new hit discovery approaches, some of which may define the next generation of therapeutic intervention strategies for epigenetic processes.

scholarly journals Small Molecule Inhibitors of Influenza Virus Entry

2021 ◽  
Vol 14 (6) ◽  
pp. 587
Author(s):  
Zhaoyu Chen ◽  
Qinghua Cui ◽  
Michael Caffrey ◽  
Lijun Rong ◽  
Ruikun Du
Keyword(s):  
Influenza Virus ◽  
Membrane Fusion ◽  
Small Molecule ◽  
Drug Target ◽  
Small Molecule Inhibitors ◽  
Virus Entry ◽  
Critical Role ◽  
Structural Basis ◽  
Future Directions ◽  
The Past

Hemagglutinin (HA) plays a critical role during influenza virus receptor binding and subsequent membrane fusion process, thus HA has become a promising drug target. For the past several decades, we and other researchers have discovered a series of HA inhibitors mainly targeting its fusion machinery. In this review, we summarize the advances in HA-targeted development of small molecule inhibitors. Moreover, we discuss the structural basis and mode of action of these inhibitors, and speculate upon future directions toward more potent inhibitors of membrane fusion and potential anti-influenza drugs.

scholarly journals Small-molecule modulators of inward rectifier K+channels: recent advances and future possibilities

2010 ◽  
Vol 2 (5) ◽  
pp. 757-774 ◽  
Author(s):  
Gautam Bhave ◽  
Daniel Lonergan ◽  
Brian A Chauder ◽  
Jerod S Denton
Keyword(s):  
Small Molecule ◽  
Inward Rectifier ◽  
K Channels ◽  
Recent Advances ◽  
Small Molecule Modulators

scholarly journals A Personal History of Using Crystals and Crystallography to Understand Biology and Advanced Drug Discovery

Crystals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 676
Author(s):  
Tom L. Blundell
Keyword(s):  
Growth Factors ◽  
Drug Discovery ◽  
Cell Surface ◽  
Small Molecule ◽  
Personal History ◽  
X Ray ◽  
Surface Receptors ◽  
The Past ◽  
Industry Collaboration ◽  
History Of

Over the past 60 years, the use of crystals to define structures of complexes using X-ray analysis has contributed to the discovery of new medicines in a very significant way. This has been in understanding not only small-molecule inhibitors of proteins, such as enzymes, but also protein or peptide hormones or growth factors that bind to cell surface receptors. Experimental structures from crystallography have also been exploited in software to allow prediction of structures of important targets based on knowledge of homologues. Crystals and crystallography continue to contribute to drug design and provide a successful example of academia–industry collaboration.

scholarly journals Targeting histone methylation for colorectal cancer

2016 ◽  
Vol 10 (1) ◽  
pp. 114-131 ◽  
Author(s):  
Tao Huang ◽  
Chengyuan Lin ◽  
Linda L. D. Zhong ◽  
Ling Zhao ◽  
Ge Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Histone Methylation ◽  
Therapeutic Effects ◽  
Epigenetic Alterations ◽  
Chemical Probes ◽  
Histone Methyltransferases ◽  
Functional Roles ◽  
Promising Target ◽  
Multiple Levels ◽  
Small Molecule Modulators

As a leading cause of cancer deaths worldwide, colorectal cancer (CRC) results from accumulation of both genetic and epigenetic alterations. Disruption of epigenetic regulation in CRC, particularly aberrant histone methylation mediated by histone methyltransferases (HMTs) and demethylases (HDMs), have drawn increasing interest in recent years. In this paper, we aim to review the roles of histone methylation and associated enzymes in the pathogenesis of CRC, and the development of small-molecule modulators to regulate histone methylation for treating CRC. Multiple levels of evidence suggest that aberrant histone methylations play important roles in CRC. More than 20 histone-methylation enzymes are found to be clinically relevant to CRC, including 17 oncoproteins and 8 tumor suppressors. Inhibitors of EZH2 and DOT1L have demonstrated promising therapeutic effects in preclinical CRC treatment. Potent and selective chemical probes of histone-methylation enzymes are required for validation of their functional roles in carcinogenesis and clinical translations as CRC therapies. With EZH2 inhibitor EPZ-6438 entering into phase I/II trials for advanced solid tumors, histone methylation is emerging as a promising target for CRC.

Polyamines: Naturally occurring small molecule modulators of electrostatic protein–protein interactions

2010 ◽  
Vol 104 (2) ◽  
pp. 118-125 ◽  
Author(s):  
Anja Berwanger ◽  
Susanne Eyrisch ◽  
Inge Schuster ◽  
Volkhard Helms ◽  
Rita Bernhardt
Keyword(s):  
Small Molecule ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Naturally Occurring ◽  
Small Molecule Modulators
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