Naslov
Bio-assays for drug safety assessment: Design, precautions and integration

Autori
Irwin, William A. ; Antolović, Roberto ; Jelić, Dubravko

Vrsta, podvrsta i kategorija rada
Poglavlja u knjigama, pregledni

Knjiga
Medicinal Chemistry in Drug Discovery. Design, Synthesis and Screening

Urednik/ci
Jelić, Dubravko

Izdavač
Transworld Research Network

Grad
Lahti

Godina
2013

Raspon stranica
301-326

ISBN
978-81-7895-560-5

Ključne riječi
HTS, HCS, bioassays, drug safety, drug design

Sažetak
High-throughput screening (HTS) is routinely employed in drug discovery to assay pipeline candidates for on-target and off-target responses (i.e. desired biological effects and safety concerns). HTS is often based on measuring thousands of drug candidates per day with a single endpoint assay, often with a single dose of compound, by utilizing absorbance, fluorescence, or luminescence methods. Conversely, microscopy-based methodologies are founded on measuring properties of a limited number of drugs per day, by using several different microscope assays with multiple drug doses, and even with kinetic measurements. FACS (fluorescence activated cell sorting) is another form of multi-channel screening technology. With automatic analysis algorithms/technologies, tedious and time consuming single-point assays can now be automated with both FACS and microscopy-based methods (i.e. mitochondrial membrane potential, lysosomal mass, cell cycle, etc.). This review will discuss the challenging aspects of in vitro bio-assay design, implementation and integration common to plate reader, FACS, microscopy, together with other aspects of screening technologies (i.e. plate layout, drug dosing, dye artifacts, data interpretation, etc.). Mitochondrial assays have become of interest to discovery toxicology, and will have particular emphasis.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA