This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003 and is able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame.
This review is an updated and expanded version of the three prior reviews and adds a new designation, "natural product botanical" or "NB", to cover those botanical "defined mixtures" that have now been recognized as drug entities by the FDA and similar organizations.
From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well, and in the area of cancer, the percentage of small molecule, new chemical entities that are nonsynthetic has remained at 62% averaged over the whole time frame.
This contribution is a completely updated and expanded version of the four prior analogous reviews that were published in this journal in 1997, 2003, 2007, and 2012, and the time frame has been extended to cover the 34 years from January 1, 1981, to December 31, 2014, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2014 for all approved antitumor drugs worldwide.
Cystatin C measurement using PETIA technology can be automated on the same instruments used routinely for the measurement of creatinine and offers better analytical performance and probably improved clinical sensitivity as a screening test for early renal damage.
Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have been used very successfully in the optimization of many recently approved agents, they are still able to identify only two de novo combinatorials compounds approved as drugs in this 39-year time frame.