Comparative mode-of-action analysis following manual and automated phenotype detection in Xenopus laevis

MedChemComm ◽  
2014 ◽  
Vol 5 (3) ◽  
pp. 386-396 ◽  
Author(s):  
Georgios Drakakis ◽  
Adam E. Hendry ◽  
Kimberley Hanson ◽  
Suzanne C. Brewerton ◽  
Michael J. Bodkin ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Xenopus Laevis ◽  
Mechanism Of Action ◽  
Mode Of Action ◽  
Action Analysis

Given the increasing utilization of phenotypic screens in drug discovery also the subsequent mechanism-of-action analysis gains increased attention.

Triazol: a privileged scaffold for proteolysis targeting chimeras

2019 ◽  
Vol 11 (22) ◽  
pp. 2919-2973 ◽  
Author(s):  
Li-Wen Xia ◽  
Meng-Yu Ba ◽  
Wei Liu ◽  
Weyland Cheng ◽  
Chao-Ping Hu ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Anticancer Activity ◽  
Mode Of Action ◽  
Critical Analysis ◽  
Enzyme Inhibitors ◽  
Structure Activity Relationship ◽  
Target Protein ◽  
Activity Relationship ◽  
Structure Activity ◽  
Privileged Scaffold

Current traditional drugs such as enzyme inhibitors and receptor agonists/antagonists present inherent limitations due to occupancy-driven pharmacology as the mode of action. Proteolysis targeting chimeras (PROTACs) are composed of an E3 ligand, a connecting linker and a target protein ligand, and are an attractive approach to specifically knockdown-targeted proteins utilizing an event-driven mode of action. The length, hydrophilicity and rigidity of connecting linkers play important role in creating a successful PROTAC. Some PROTACs with a triazole linker have displayed promising anticancer activity. This review provides an overview of PROTACs with a triazole scaffold and discusses its structure–activity relationship. Important milestones in the development of PROTACs are addressed and a critical analysis of this drug discovery strategy is also presented.

Mechanism of Action of Niacin: Implications for Atherosclerosis and Drug Discovery

2011 ◽  
pp. 235-251
Author(s):  
Devan Marar ◽  
Shobha H. Ganji ◽  
Vaijinath S. Kamanna ◽  
Moti L. Kashyap
Keyword(s):  
Drug Discovery ◽  
Mechanism Of Action

scholarly journals The Phosphoenolpyruvate:Sugar Phosphotransferase System Is Involved in Sensitivity to the Glucosylated Bacteriocin Sublancin

2015 ◽  
Vol 59 (11) ◽  
pp. 6844-6854 ◽  
Author(s):  
C. V. Garcia De Gonzalo ◽  
E. L. Denham ◽  
R. A. T. Mars ◽  
J. Stülke ◽  
W. A. van der Donk ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Mechanism Of Action ◽  
Mode Of Action ◽  
Phosphotransferase System ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Distinct Mechanism ◽  
Genomic Studies ◽  
Increased Sensitivity ◽  
Bacterial Sensitivity

ABSTRACTThe mode of action of a group of glycosylated antimicrobial peptides known as glycocins remains to be elucidated. In the current study of one glycocin, sublancin, we identified the phosphoenolpyruvate:sugar phosphotransferase system (PTS) ofBacillusspecies as a key player in bacterial sensitivity. Sublancin kills several Gram-positive bacteria, such asBacillusspecies andStaphylococcus aureus, including methicillin-resistantS. aureus(MRSA). Unlike other classes of bacteriocins for which the PTS is involved in their mechanism of action, we show that the addition of PTS-requiring sugars leads to increased resistance rather than increased sensitivity, suggesting that sublancin has a distinct mechanism of action. Collectively, our present mutagenesis and genomic studies demonstrate that the histidine-containing phosphocarrier protein (HPr) and domain A of enzyme II (PtsG) in particular are critical determinants for bacterial sensitivity to sublancin.

Multivariate mode-of-action analysis of acute toxicity of phenols

1997 ◽  
Vol 38 (4) ◽  
pp. 277-296 ◽  
Author(s):  
Gerrit Schüürmann ◽  
Helmut Segner ◽  
Klaus Jung
Keyword(s):  
Acute Toxicity ◽  
Mode Of Action ◽  
Action Analysis ◽  
Multivariate Mode

scholarly journals Connecting gene expression data from connectivity map and in silico target predictions for small molecule mechanism-of-action analysis

2015 ◽  
Vol 11 (1) ◽  
pp. 86-96 ◽  
Author(s):  
Aakash Chavan Ravindranath ◽  
Nolen Perualila-Tan ◽  
Adetayo Kasim ◽  
Georgios Drakakis ◽  
Sonia Liggi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ligand Binding ◽  
Gene Expression Data ◽  
Mechanism Of Action ◽  
In Silico ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Expression Data ◽  
Connectivity Map ◽  
Action Analysis

Integrating gene expression profiles with certain proteins can improve our understanding of the fundamental mechanisms in protein–ligand binding.

Development of a High-Content Screening Assay Panel to Accelerate Mechanism of Action Studies for Oncology Research

2012 ◽  
Vol 17 (8) ◽  
pp. 1005-1017 ◽  
Author(s):  
Danli L. Towne ◽  
Emily E. Nicholl ◽  
Kenneth M. Comess ◽  
Scott C. Galasinski ◽  
Philip J. Hajduk ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Mechanism Of Action ◽  
Large Scale ◽  
Morphological Changes ◽  
Single Cells ◽  
High Content Screening ◽  
Individual Compound ◽  
Screening Assay ◽  
Oncology Research ◽  
Protein Functions

Efficient elucidation of the biological mechanism of action of novel compounds remains a major bottleneck in the drug discovery process. To address this need in the area of oncology, we report the development of a multiparametric high-content screening assay panel at the level of single cells to dramatically accelerate understanding the mechanism of action of cell growth–inhibiting compounds on a large scale. Our approach is based on measuring 10 established end points associated with mitochondrial apoptosis, cell cycle disruption, DNA damage, and cellular morphological changes in the same experiment, across three multiparametric assays. The data from all of the measurements taken together are expected to help increase our current understanding of target protein functions, constrain the list of possible targets for compounds identified using phenotypic screens, and identify off-target effects. We have also developed novel data visualization and phenotypic classification approaches for detailed interpretation of individual compound effects and navigation of large collections of multiparametric cellular responses. We expect this general approach to be valuable for drug discovery across multiple therapeutic areas.

Mechanism of Action of Progestins in the Treatment of Hormone-dependent Breast Cancer.

1975 ◽  
Vol 61 (6) ◽  
pp. 501-508 ◽  
Author(s):  
Francesco Di Carlo ◽  
Giovanni Pacilio ◽  
Giuseppe Conti
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptors ◽  
Mechanism Of Action ◽  
Mode Of Action ◽  
Binding Capacity ◽  
Specific Receptors ◽  
High Concentrations ◽  
Good Agreement

The in vitro interference of some gestagens with the binding of 3H-17 β-oestradiol to cytosol specific receptors was investigated with a view to elucidating the mechanism of action of progestins in the treatment of human hormone-dependent breast cancer. A decrease (up to 85 %) of oestradiol binding capacity was observed with high concentrations of progesterone, clogestone and medrogestone. These findings are in good agreement with those previously obtained by the same progestins in our laboratory on rat uterine estrogen receptors in vitro or in vivo. These results provide support for the hypothesis that the mode of action of progestins in the therapy of mammary and perhaps uterine carcinomas is to some extent related to the inhibition of oestradiol binding to cytosol specific receptors.

scholarly journals Targeting secondary protein complexes in drug discovery: studying the druggability and chemical biology of the HSP70/BAG1 complex

2017 ◽  
Vol 53 (37) ◽  
pp. 5167-5170 ◽  
Author(s):  
Lindsay E. Evans ◽  
Keith Jones ◽  
Matthew D. Cheeseman
Keyword(s):  
Drug Discovery ◽  
Mechanism Of Action ◽  
Chemical Biology ◽  
Protein Complexes

A non-nucleotide FP-probe was designed to study the mechanism of action and druggability of the secondary HSP70/BAG1 complex.

Antidepressant Drugs and Migraine

Cephalalgia ◽  
1985 ◽  
Vol 5 (2_suppl) ◽  
pp. 225-228 ◽  
Author(s):  
N Martucci ◽  
V Manna ◽  
A Agnoli
Keyword(s):  
Mechanism Of Action ◽  
Clinical Studies ◽  
Mode Of Action ◽  
Antidepressant Drugs ◽  
Antidepressant Activity

There is evidence that some antidepressant drugs, above all amitriptyline and mianserine, are beneficial in the prophylaxis of migraine. The mechanism of action of antidepressants in migraine is likely to be complex. Mood disturbances accompanying migraine syndromes suggest a mode of action of such a class of drugs. In the last few years some clinical studies tend to show that the antimigraine effects of these drugs seem relatively independent of the antidepressant activity.

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