Biological data, evaluation

For all three compounds, biological data relevant to the evaluation of carcinogenic risk to humans are summarized in the World Health Organization International Agency for Research on Cancer monograph (70). 

The book is separated into five major sections One short section on general aspects of spectroscopy, molecular biology and data evaluation is followed by an introduction into the NMR of commonly encountered classes of biomolecules. Thereafter, recent developments in spectroscopic techniques are highlighted. The next section describes experiments and practical aspects useful for the characterization of protein-ligand interactions. The final section presents an account on strategies for drug development using NMR written by experts from pharmaceutical industry. 

Similar data evaluation problems exist in other scientific fields and can also be treated by multivariate statistical data analysis, for instance, in economics (econometrics), sociology, psychology (psychometrics), medicine, biology (chemotaxonomy),... 

Classical Drug Discovery focused on the biological evaluation of individual purified compounds. But in light of HTS and combinatorial chemistry, it became widely accepted that the biological screening of mixtures of compounds should, in theory, provide much more biological data in the same amount of time used for bioassay of individual compounds,... 

Atkinson, R., D. L. Baulch, R. A. Cox, R. F. Hampson, J. A. Kerr, M. J. Rossie, and J. Troe, Evaluated Kinetic and Photochemical Data for Atmospheric Chemistry. Supplement V. IUPAC Subcommittee on Gas Kinetic Data Evaluation for Atmospheric Chemistry, J. Phys. Chem. Ref. Data, 26, 521-1011 (1997). Bordewijk, J. A., H. Slaper, H. A. J. M. Reinen, and E. Schlamann, Total Solar Radiation and the Influence of Clouds and Aerosols on the Biologically Effective UV, Geophys. Res. Lett., 22, 2151-2154 (1995). 

Lehnert. G. and D. Henschier Biological Exposure Values for Occupational Toxicants and Carcinogens Substances Critical Data Evaluation for Bat and Eka Values. Vol. 3, John Wiley Sons. Tnc., New York. NY. 1998. 

Twenty-Eight- to Ninety-Day Tests. Chemicals are usually tested by administration in the diet, less commonly in the drinking water, and only when absolutely necessary by gavage, because the last process involves much handling and subsequent stress. Numerous experimental variables must be controlled and biologic variables evaluated. In addition the number of end points that can be measured is large, and as a consequence record keeping and data analysis must be carefully planned. If all is done with care, much may be learned from such tests. 

Table 6-4. Biological evaluation of phytotoxicity of metal contaminated substrates with Phaseolus vulgaris as the test plant. Classification of biological data into phytotoxicity classes, depending on the magnitude of the effect (% of control for morphological parameters and enzymes capacities) (after Van Assche and Clijsters, 1990 Vangronsveld and Clijsters, 1992).

C21-Amino-Epo B [BMS-310705 (23)] is undergoing clinical evaluation in humans, but only hmited biological data are currently available in the literature for this compound. Thus, an IC50 value of 0.8 nM for growth inhibition of the human epidermoid cancer cell line KB.31 has been reported in a patent application (vs 1.2nM for Epo B under comparable experimental conditions" ). More recently, Uyar et al." have demonstrated that 50 nM BMS-310705 induces substantial apoptosis in early passage ovarian cancer cells (OC-2), which were derived from a clinical tumor sample and were refractory to paclitaxel and platinum treatment. A concentration of 50 nM of BMS-310705 (23) is clinically achievable at a dose of 10 mg/m, which is below the phase 1 maximum tolerated dose (MTD) for the compound. " BMS-310705 (23) exhibits improved water-solubility over BMS-247550 (1), which enables the use of chnical formulations not containing Cremophor-EL. ... 

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