Leads from HTS

Lahana R. How many leads from HTS Drug Discov Today 1999 4 447-8. 

In generating leads from HTS of corporate compound collections and from focused libraries, there are clearly multiple tools and strategies this situation likely reflects... 

Simply finding leads from HTS or other assays is insufficient evidence since it is conceivable that almost any reasonably sized collection of compounds can yield active compounds. Moreover, leads from a designed library can improve the probability of finding bioactivity but will not necessarily give rise to compounds of higher efficacy or in larger numbers than those from other libraries. 

R. Lahana, Drug Discovery Today, 4, 447 (1999). How Many Leads from HTS ... 

Some aspects of this parallel drug design environment were evident in the pages of J. Med. Chem. in 2001, for example, leads from HTS of designed... 

Overview of Hit to Lead The Medicinal Chemist s Role from HTS Retest to Lead Optimization Hand Off. 1... 

Sherlock JC, Ashby D, Delves HT, et al. 1984. Reduction in exposure to lead from drinking water and its effect on blood lead concentrations. Human Toxicol 3 383-392. 

FIGURE 18.4 Pharmacologist s view of emetic stimuli. Myriad signaling pathways lead from the periphery to the emetic center. Stimulants of these pathways are noted in italics. These pathways involve specific neurotransmitters and their receptors (bold text). Receptors are shown for dopamine, D acetylcholine (muscarinic), M histamine, H and 5-hydroxytryptamine, 5-HT. Some of these receptor types also may mediate signaling in the emetic center. This knowledge offers a rationale for current antiemetic therapy. 

Hit rates from HTS are often low and the hits obtained fail to progress into lead optimisation HTS is the predominant technique for hit finding employed by the majority of pharmaceutical companies and is central to modern drug discovery. However, many scientists are now regarding HTS as a costly necessity rather than a method of choice.191... 

Baxter et al. have nicely demonstrated that one can take a 0.9 xM hit, discovered from HTS, to an 11 nM K compound.1341 An X-ray crystal structure of the HTS lead helped demonstrate the unique binding pose in the active site which only occupied the non prime side of BACE-1 in a hairpin orientation. The crystal structure revealed that the prime side was not occupied and the incorporation of a cyclohexyl ring resulted in a potent 11 nM compound.1331... 

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