Examining the evidence of non-monotonic dose-response in Androgen Receptor agonism high-throughput screening assay was written by Klimenko, Kyrylo. And the article was included in Toxicology and Applied Pharmacology in 2021.Category: amides-buliding-blocks This article mentions the following:
Modern High-Throughput Screening (HTS) techniques allow to determine in vitro bioactivity of tens of thousands of chems. within a relatively short period of time and tested compounds are usually interpreted as either active or inactive. The interpretation is mostly based on the assumption of monotonic dose-response. This approach ignores potential abnormal dose-response relationships, such as non-monotonic dose-response (NMDR). NMDR presents a serious challenge to toxicologists and pharmacologists, since they undermine the usefulness of such concepts as lowest-observed-adverse-effect level (LOAEL) and no-observed-adverse-effect level (NOAEL). The possible presence of the NMDR in Androgen receptor (AR) agonism was examined for a structurally diverse set of chems. (∼8 300 unique compounds) from Tox21 project library. The source of activity data is Tox21 AR agonism luciferase-based HTS on the MDA-MB-453 cell line. The examination of curve fitting for 35,328 dose-response data entries was based on modified version of existing criteria for determination of NMDR. The bias that arises from compounds’ cytotoxicity and interference with firefly luciferase protein was also studied. The examination has shown evidence of NMDR for several compounds, including known AR antagonists (e. g. Cyproterone acetate) and other known endocrine disruptors (e. g. Tranilast). Compounds were divided into 3 groups based on chem. class, known biol. activity profile and the shape of dose-response curve. The challenges of using HTS data to determine NMDR and benefits of this anal. are discussed. In the experiment, the researchers used many compounds, for example, 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8Category: amides-buliding-blocks).
2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8) belongs to amides. Compared to amines, amides are very weak bases and do not have clearly defined acid–base properties in water. On the other hand, amides are much stronger bases than esters, aldehydes, and ketones. The presence of the amide group –C(=O)N– is generally easily established, at least in small molecules. It can be distinguished from nitro and cyano groups in IR spectra. Amides exhibit a moderately intense νCO band near 1650 cm−1. By 1H NMR spectroscopy, CONHR signals occur at low fields. In X-ray crystallography, the C(=O)N center together with the three immediately adjacent atoms characteristically define a plane.Category: amides-buliding-blocks
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics