Phenotypic Screening of Small-Molecule Inhibitors: Implications for Therapeutic Discovery and Drug Target Development in Traumatic Brain Injury

2016 ◽  
pp. 677-688 ◽  
Author(s):  
Hassan Al-Ali ◽  
Vance P. Lemmon ◽  
John L. Bixby
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Small Molecule ◽  
Drug Target ◽  
Small Molecule Inhibitors ◽  
Phenotypic Screening

scholarly journals A small molecule p75NTRligand protects neurogenesis after traumatic brain injury

Stem Cells ◽  
2013 ◽  
Vol 31 (11) ◽  
pp. 2561-2574 ◽  
Author(s):  
Jian Shi ◽  
Frank M. Longo ◽  
Stephen M. Massa
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Small Molecule

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 Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders

2021 ◽  
Vol 22 (9) ◽  
pp. 4333
Author(s):  
Yutaka Koyama
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurotrophic Factors ◽  
Drug Target ◽  
Therapeutic Strategy ◽  
Reactive Astrocytes ◽  
Brain Disorders ◽  
Etb Receptor ◽  
Target Molecules ◽  
Endothelin B

In brain disorders, reactive astrocytes, which are characterized by hypertrophy of the cell body and proliferative properties, are commonly observed. As reactive astrocytes are involved in the pathogenesis of several brain disorders, the control of astrocytic function has been proposed as a therapeutic strategy, and target molecules to effectively control astrocytic functions have been investigated. The production of brain endothelin-1 (ET-1), which increases in brain disorders, is involved in the pathophysiological response of the nervous system. Endothelin B (ETB) receptors are highly expressed in reactive astrocytes and are upregulated by brain injury. Activation of astrocyte ETB receptors promotes the induction of reactive astrocytes. In addition, the production of various astrocyte-derived factors, including neurotrophic factors and vascular permeability regulators, is regulated by ETB receptors. In animal models of Alzheimer’s disease, brain ischemia, neuropathic pain, and traumatic brain injury, ETB-receptor-mediated regulation of astrocytic activation has been reported to improve brain disorders. Therefore, the astrocytic ETB receptor is expected to be a promising drug target to improve several brain disorders. This article reviews the roles of ETB receptors in astrocytic activation and discusses its possible applications in the treatment of brain disorders.

scholarly journals Microglia: A Potential Drug Target for Traumatic Axonal Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xin Huang ◽  
Wendong You ◽  
Yuanrun Zhu ◽  
Kangli Xu ◽  
Xiaofeng Yang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Drug Target ◽  
Microglial Activation ◽  
Axonal Injury ◽  
Traumatic Axonal Injury ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Microglial Phenotype ◽  
M2 Phenotype

Traumatic axonal injury (TAI) is a major cause of death and disability among patients with severe traumatic brain injury (TBI); however, no effective therapies have been developed to treat this disorder. Neuroinflammation accompanying microglial activation after TBI is likely to be an important factor in TAI. In this review, we summarize the current research in this field, and recent studies suggest that microglial activation plays an important role in TAI development. We discuss several drugs and therapies that may aid TAI recovery by modulating the microglial phenotype following TBI. Based on the findings of recent studies, we conclude that the promotion of active microglia to the M2 phenotype is a potential drug target for the treatment of TAI.

scholarly journals Attenuation of traumatic brain injury-induced cognitive impairment in mice by targeting increased cytokine levels with a small molecule experimental therapeutic

2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Adam D Bachstetter ◽  
Scott J Webster ◽  
Danielle S Goulding ◽  
Jonathan E Morton ◽  
D Martin Watterson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cognitive Impairment ◽  
Brain Injury ◽  
Small Molecule ◽  
Cytokine Levels

scholarly journals Identification of a Class of Small Molecule Inhibitors of the Sirtuin Family of NAD-dependent Deacetylases by Phenotypic Screening

2001 ◽  
Vol 276 (42) ◽  
pp. 38837-38843 ◽  
Author(s):  
Christina M. Grozinger ◽  
Elizabeth D. Chao ◽  
Helen E. Blackwell ◽  
Danesh Moazed ◽  
Stuart L. Schreiber
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Phenotypic Screening

scholarly journals A Primary Evaluation of Potential Small‐Molecule Inhibitors of the Astacin Metalloproteinase Ovastacin, a Novel Drug Target in Female Infertility Treatment

ChemMedChem ◽  
2020 ◽  
Vol 15 (16) ◽  
pp. 1499-1504 ◽  
Author(s):  
Hagen Körschgen ◽  
Christian Jäger ◽  
Kathrin Tan ◽  
Mirko Buchholz ◽  
Walter Stöcker ◽  
...  
Keyword(s):  
Small Molecule ◽  
Drug Target ◽  
Small Molecule Inhibitors ◽  
Infertility Treatment ◽  
Female Infertility ◽  
Primary Evaluation ◽  
Novel Drug

scholarly journals A Small Molecule Spinogenic Compound Enhances Functional Outcome and Dendritic Spine Plasticity in a Rat Model of Traumatic Brain Injury

2019 ◽  
Vol 36 (4) ◽  
pp. 589-600 ◽  
Author(s):  
Yanlu Zhang ◽  
Michael Chopp ◽  
Christopher S. Rex ◽  
Vincent F. Simmon ◽  
Stella T. Sarraf ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Functional Outcome ◽  
Small Molecule ◽  
Rat Model ◽  
Dendritic Spine ◽  
Spine Plasticity

scholarly journals Phenotypic Screening for Kinase Targets Using Small Molecule Inhibitors with Proven Cell Penetration

2013 ◽  
Vol 24 ◽  
pp. i18
Author(s):  
J. Winkler ◽  
L. Burgess ◽  
E. Laird ◽  
D. Weaver ◽  
D. Chantry
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Phenotypic Screening ◽  
Cell Penetration

scholarly journals Small Molecule Inhibitors of HSF1-Activated Pathways as Potential Next-Generation Anticancer Therapeutics

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2757 ◽  
Author(s):  
Chiranjeev Sharma ◽  
Young Seo
Keyword(s):  
Small Molecule ◽  
Drug Target ◽  
Small Molecule Inhibitors ◽  
Chemotherapeutic Agents ◽  
Heat Shock Factor 1 ◽  
Next Generation ◽  
Anticancer Activities ◽  
Cancer Cell Growth ◽  
Survival Studies ◽  
New Chemotherapeutic Agents

Targeted therapy is an emerging paradigm in the development of next-generation anticancer drugs. Heat shock factor 1 (HSF1) has been identified as a promising drug target because it regulates several pathways responsible for cancer cell growth, metastasis, and survival. Studies have clearly demonstrated that HSF1 is an effective drug target. Herein, we provide a concise yet comprehensive and integrated overview of progress in developing small molecule inhibitors of HSF1 as next-generation anticancer chemotherapeutics while critically evaluating their potential and challenges. We believe that this review will provide a better understanding of important concepts helpful for outlining the strategy to develop new chemotherapeutic agents with promising anticancer activities by targeting HSF1.

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