Chemical biological testing

The area of nonsteroidal antiestrogens along with other classes of nonsteroidal antagonists of sex-steroid hormone action has been reviewed to 1986, and these compounds have been grouped by chemical stmcture as a basis of classification rather than any biochemical or biological test system utilized to assess antagonist activity (46). 

In additional EPA studies, subchronic inhalation was evaluated ia the rat for 4 and 13 weeks, respectively, and no adverse effects other than nasal irritation were noted. In the above-mentioned NTP chronic toxicity study ia mice, no chronic toxic effects other than those resulting from bronchial irritation were noted. There was no treatment-related increase ia tumors ia male mice, but female mice had a slight increase in bronchial tumors. Neither species had an increase in cancer. Naphthalene showed no biological activity in other chemical carcinogen tests, indicating Htde cancer risk (44). No incidents of chronic effects have been reported as a result of industrial exposure to naphthalene (28,41). 

P Willett, V Wmterman, D Bawden. Implementation of nonhierarchic cluster analysis methods m chemical information systems Selection of compounds for biological testing and clustering of substiaictures search output. I Chem Inf Comput Sci 26 109-118, 1986. 

Quality Chemical, Pharmaceutical and Biological Testing of Medicinal Products 11... 

The FDA did not include outlier tests in the USP for chemical assays, but allowed the practice for biological tests. The reason for this could be that because of the high precision, n is usually small in chemical testing with n < 3, outlier tests cannot be conducted. It appears that Judge Wolin followed this recommendation when deliberating his decision. 

The half-life of the 2,3,7,8-tetrachlorodibenzo-p-dioxin in isooctane was estimated to be 40 min for the 0.5 meter exposure and 3 hours for the one meter exposure. The half-life in 1-octanol was essentially the same. The 24-hour photolysis products of the 2,3,7,8-tetrachlorodibenzo-p-dioxin were examined by gas chromatography. The smallest concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that could be detected by the instrument was 0.5 ppm. When an injection of the 24-hour photolysis product was made, no tetra was detected. An additional confirmation of the disappearance of the 2,3,7,8-tetrachlorodibenzo-p-dioxin in the 24-hour photolysis products was obtained when thej yiaterial was submitted to the Chemical-Biology Research Laboratory for rabbit testing. No chloracnegenic activity was indicated. ... 

The previous sections have summarized the basic techniques available for searching chemical databases for specific types of query. Another important database application is compound selection, the ability to select a subset of a database for submission to a biological testing program. The selection procedure can be applied to in-house databases, to externally available compound collections, or to virtual libraries, that is, sets of compounds that could potentially be synthesized. 

Willett P, Winterman V, Bawden DJ. Implementation of non hierarchical cluster-analysis methods in chemical information-systems-selection of compounds for biological testing and clustering of substructure search output. Chem Inf Comp Sci 1986 26 109-18. 

The same template as for compound 71 was used by Peukert et al. for a 2D similarity search in the Aventis in-house compound collection [144]. 75 Compounds with a similarity index >0.80 were biologically tested. The moderately active l-carboxy,8-sulfonamido-naphthalene (IC50 = 9.5pM), with insufficient chemical stability, was the starting point for the design of substi-... 

The flask is rotated using a standard chemical/biologic shaker to swirl the contents. Results show that all high-energy tests (the Mackay, the Laboflna, and the oscillating hoop) produce unique dispersant effectiveness results that correlate poorly with the physical properties of the oil. 

Chemicals, Inc., who conducted the biological tests and assisted in the compilation of the data. 

Table II. Several of the reactions outlined in Table II were discussed under the chemical reactions of DFDT. In general, the DFDT analogs listed here were prepared in the laboratory for the purpose of producing a sample of the material for biological testing rather than to study the several reactions involved or to improve the yields. The latter were usually omitted in the literature.

The third step is to optimize the lead molecule through iterative chemical synthesis and biological testing, aiming to obtain molecules with the required potency (typically nanomolar), selectivity, bioavailability, and DMPK (drug metabolism and pharmacokinetics) properties. This step usually requires considerable time and resources usually the synthesis of hundreds of compounds is needed to deduce a robust SAR (structure-activity relationship). Such resources can be considerably reduced and the... 

The power of the pooled GST fusion protein approach will increase as new biochemical reagents and assays become available. The development of chemical probes for biological processes, termed chemical biology, is a rapidly advancing field. For example, the chemical synthesis of an active site directed probe for identification of members of the serine hydrolase enzyme family has recently been described (Liu et al., 1999). The activity of the probe is based on the potent and irreversible inhibition of serine hydrolases by fluorophosphate (FP) derivatives such as diisopropyl fluorophosphate. The probe consists of a biotinylated long-chain fluorophosphonate, called FP-biotin (Liu et al., 1999). The FP-biotin was tested on crude tissue extracts from various organs of the rat. These experiments showed that the reagent can react with numerous serine hydrolases in crude extracts and can detect enzymes at subnanomolar... 

Woolery, D. O. Thornton, K. Lian, N. D. Hunter, S. A. Abbreviated Test Report for the Chemical Performance Retest of the Chemical Biological Mass... 

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