The Problems of Applying Classical Pharmacology Analysis to Modern In Vitro Drug Discovery Assays: Slow Binding Kinetics and High Target Concentration

Autor: Sam R J Hoare

Publikováno v: SLAS Discovery. 26:835-850

The analysis framework used to quantify drug potency in vitro (e.g., Kd or Ki) was initially developed for classical pharmacology bioassays, for example, organ bath experiments testing moderate-affinity natural products. Modern drug discovery can inf

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5d22325d8931350092be022f8e29261a
https://doi.org/10.1177/24725552211019653

High-content phenotypic and pathway profiling to advance drug discovery in diseases of unmet need

Autor: Rebecca E. Hughes, John C. Dawson, Neil O. Carragher, Richard J. R. Elliott

Publikováno v: Hughes, B, Elliott, R, Dawson, J C & Carragher, N O 2021, ' High content phenotypic and pathway profiling to advance drug discovery in diseases of unmet need ', Cell Chemical Biology . https://doi.org/10.1016/j.chembiol.2021.02.015

Conventional thinking in modern drug discovery postulates that the design of highly selective molecules which act on a single disease-associated target will yield safer and more effective drugs. However, high clinical attrition rates and lack of prog

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::27e56b1a4730709aaf2f24876f58cf5f
https://doi.org/10.1016/j.chembiol.2021.02.015

A High-Throughput Assay for the Pancreatic Islet Beta-Cell Potassium Channel: Use in the Pharmacological Characterization of Insulin Secretagogues Identified from Phenotypic Screening

Autor: Samreen K. Syed, David Gene Barrett, Francis S. Willard, Karen Leigh Cox, Dirk Tomandl, Alexander M. Efanov, Luyan Song

Publikováno v: ASSAY and Drug Development Technologies. 19:27-37

Phenotypic screening is a neoclassical approach for drug discovery. We conducted phenotypic screening for insulin secretion enhancing agents using INS-1E insulinoma cells as a model system for pancreatic beta-cells. A principal regulator of insulin s

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::56b9ab4bd48304b142f94dca349233cb
https://doi.org/10.1089/adt.2020.1011

Z’ Does Not Need to Be > 0.5

Autor: Adam Zweifach, Haim Bar

Publikováno v: SLAS Discovery. 25:1000-1008

The assay metric Z' has come to play a critical gatekeeping role in determining whether high-throughput assays can be performed. While Z' is commonly required to be > 0.5, this expectation is not well supported. Requiring Z' > 0.5 likely prevents man

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::b2711942e15d4b2c50130080b6055f8d
https://doi.org/10.1177/2472555220942764

Combined siRNA and Small-Molecule Phenotypic Screening Identifies Targets Regulating Rhinovirus Replication in Primary Human Bronchial Epithelial Cells

Autor: Elisabeth Bäck, Jörgen Östling, Mei Ding, Christopher McCrae, Christian Tyrchan, Steffen Schubert

Publikováno v: SLAS Discovery. 25:634-645

Human rhinovirus (RV) is the most common cause of acute upper respiratory tract infections and has recently been shown to play a significant role in exacerbations of asthma and chronic obstructive pulmonary disease (COPD). There is a significant unme

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::39b4f8369a5524d8f0b23da8d2f65f89
https://doi.org/10.1177/2472555220909726