Compounds are arranged by common name; these non-systemic trivial designations range the way from the USAN (US Adopted Name, generic name) for some commercial products, to supplier's code numbers for some of the more recent entries.
Chemical Structure
Chemical structure is displayed in 2D form as an image captured from the DTP's Drug Information System. The 3D coordinates are accessible by clicking on the 2D picture. The 3D coordinates are served in the MDL molfile format. These 3D coordinates were generally generated from the 2D connection tables by the program Corina. In some cases additional geometry optimization was done, but in no case was there any extensive search for a global energy minimum.
Chemical Names
Chemical Name is taken directly from Chemical Abstracts. Older entries are formatted in the inverted order listed by CAS; these have been reversed for more current compounds. A few very recent entries are not yet listed in that data base; those few compounds of course also lack the CAS Registry Number.
Biological Data
Activity In Human Tumor Cell Line Screen
The NCI cancer screen measures growth inhibition against a panel of human tumor cell lines. The data is presented in a number of formats:
- The meangraph format is served as a postscript file. The user can download and print this file or configure a postscript viewer, such as ghostscript. We have had very little success using ghostscript to view these files on Windows machines.
- The table format is an html file that provides a nested look at the cell panels and each individual cell line.
Toxicity Data
It had been the practice in the earlier editions to include data on the acute and sometimes chronic toxicity data on compounds. This data was derived from the Registry of Toxic Effects of Chemical Substances compiled by the National Institute of Occupational Safety and Health, the Toxicology Branch (NCI) and in vivo screening data (NCI). The growing list of compounds which were included in the book in recent years precluded addition of such data for each compound. Listings from previous editions are carried over into this edition as they may still be useful to some users.
Chemical Data
Approximate Solubility
It was the practice earlier to develop a rather extensive solubility profile on new compounds in a wide range of solvents including non-polar organic media. Those studies were intended only to provide rough solubility estimates rather than precise values. Data on more recent compounds comes mainly from formulation development work. The fact that the majority of NCI agents are intended for parenteral administration means that more recent solubility data shows a marked emphasis on aqueous media.
Stability
Data on Bulk stability is intended to serve as a guide to conditions for storing unformulated compound. Solution stability data usually involves aqueous media; much of this data is obtained from formulation studies.
Ultraviolet Absorption
The absorption maxima listed for compounds will probably prove useful mainly for assay development since UV is seldom used currently to characterize compounds; when extinction coefficients are listed as single values rather than ranges these should be considered approximations.High Performance Liquid Chromatography
Almost all quantitative assays for agents listed in this book consist of HPLC methods. NCI analytical contractors are expected to routinely validate those methods before they are used for assay of IND directed samples. While most of the HPLC methods listed in this book have been validated for bulk drug substance, they may also be suitable for formulated drug. The experienced chromatographer will recognize that there exists very large variations between various vendors' brands of HPLC columns; it is well recognized that it is not sufficient to specify C-18 or ODS. The description of the method consequently includes the brand of column used when the method was validated. This is not to say that other brands of columns may not in fact work just as well or even better. Listings of retention volumes without ranges does not imply that those need be considered invariant.