Biomedical Engineering Reference
In-Depth Information
Lead discovery strategies for both,pharmaceutical,and agrochemical appli-
cations are in a highly rapid developmental stage. The driving force is the re-
duction in the time to reach the market for new drugs which requires dramatic
performance improvements in lead finding and development. Success and
failure are tremendously coupled to both,the novelty and meaningfulness ofthe
applied biological test systems,and the number and structural diversity of test
compounds available.Unambiguous infrastructural elements for effective HTS
are target discovery and evaluation, screen design, sample sourcing, robotic
hardware, and data management. Therefore, laboratory automation is an in-
dispensible tool for the efficiency in HTS, and plays a crucial role in the early
lead-finding stages of drug discovery.The deployment of automation bears key
benefits.These include the potential for increased reliability and precision,and
reduced error frequency arising from removal of operator tedium.
In a first order,drug discovery strategies can be divided into the following
parts:
i) accessing structural diversity either from natural sources or from synthetic
approaches,
ii) sample preparation and handling,
iii) the screening based on new and significant biological assay systems,
iv) the profiling of so-called hits from the primary screening,and
v) data management.
Today,a number of pharmaceutical companies dealing with HTS reach a turn-
over of more than 15 different assay systems a year,in which 300,000 samples or
even more are tested.This confronts the scientist with more than 5,000,000 data
points which point to the need for efficient automation at all stages ofHTS,even
in data collection, data quality control and analysis. Robots, especially large
systems integrated with multiple peripheral devices,are prominent at present.
In order to take real advantage of HTS,access to high sample numbers cover-
ing a broad range of low-molecular mass diversity is essential. The answer of
organic chemistry to high capacities in testing was combinatorial chemistry.
The answer for natural product chemistry is still pending.Combinatorial bio-
chemistry aims at enhancing molecular diversity ofnatural products by altering
and combining of biosynthetic genes.Although,these promising strategies may
probably contribute substantially to HTS test sample supply in future,improve-
ments that can be realized more rapidly are needed urgently to decrease the
delay of innovation, and to focus attention of the management boards in the
pharmaceutical companies again towards natural products based test sampling.
2
Natural Product-derived Drugs on the Market
The accidental discovery of penicillin in 1928 by Alexander Fleming and its
introduction in 1941/42 as an efficient antibacterial drug bearing no substantial
side effects revolutionized medicinal chemistry and pharmaceutical research by
stimulating completely new strategies in industrial drug discovery. Penicillin
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