ABSTRACT
The use of in silico predictions for the assessment of bacterial mutagenicity under the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M7 guideline is recommended when two complementary (quantitative) structure-activity relationship (Q)SAR models are used. Using two systems may increase the sensitivity and accuracy of predictions but also increases the need to review predictions, particularly in situations where results disagree. During the 4th ICH M7/QSAR Workshop held during the Joint Meeting of the 6th Asian Congress on Environmental Mutagens (ACEM) and the 48th Annual Meeting of the Japanese Environmental Mutagen Society (JEMS) 2019, speakers demonstrated their approaches to expert review using 20 compounds provided ahead of the workshop that were expected to yield ambiguous (Q)SAR results. Dr. Chris Barber presented a selection of the reviews carried out using Derek Nexus and Sarah Nexus provided by Lhasa Limited. On review of these compounds, common situations were recognised and are discussed in this paper along with standardised arguments that may be used for such scenarios in future.
ABSTRACT
The CCR5 chemokine receptor is expressed on a wide range of immune cell types and binding to this receptor mediates cellular entry by the majority of HIV isolates. Blocking viral entry via this receptor reduces the viral load in patients infected with HIV, suggesting that a CCR5 antagonist could become a key component in the treatment of HIV-compromised patients. A number of CCR5 antagonists are currently in clinical trials. This review details the status of leading agents and highlights recent advances in the development of new CCR5 antagonists.
