Development thalidomide

Thalidomide was born out of the Pharmaceutical Industry in the 1950s. At that time the Pharmaceutical Industry comprised a multitude of competing Companies, many of which were not dedicated to drug development, with few or no laws governing development and marketing. Chemie-Griinenthal, who developed thalidomide, was a subsidiary of a soap and cosmetics manufacturer (Dali Werke, Maurer, and Wirtz). Many new medicines were simple concoctions... 

Development of novel response modifiers derived from thalidomide (3-phthaIimidopyridine-2,6-dione) and other phthalimide derivatives 99 YGK94. 

The thalidomide analogs CPS49 (30) and CPS11 (31) have been reported to inhibit PI3/AKT signaling in multiple myeloma cells via an anti-angiogenic effect. These compounds are devoid of the teratogenic properties seen with thalidomide and are currently in preclinical development [66]. Compound 30, and to a lesser extent 31, induced a dose-dependent inhibition of proliferation in several multiple myeloma cell lines and reduced phospho-AKT levels [66]. These compounds also inhibited DNA synthesis in cell lines resistant to conventionally used anti-multiple myeloma drugs (e.g. dexamethasone, anthracyclines and melphalan) in a dose-dependent manner. 

The ideal solubility equation has significant value in chiral systems, where a single enantiomer is desired as the product [20]. The behaviour of chiral compounds is very important in biological systems and in drug development, where it is typical for just one enantiomer of an API to be biologically active. The undesired enantiomer may be inert, or possess more serious toxicity effects, as in the case of Thalidomide. Many enantiomeric systems form three discrete solid phases, depending on the solution concentration. Pure crystals of each enantiomer will form at high concentrations of their respective enantiomer. At... 

However, it had not been discovered that the thalidomide drug molecule could cross the placental barrier and affect fetal development. As a result, thousands of babies were born with crippled extremities, disfigurement, and disabilities. Numerous fetuses were stillborn or died soon after birth. 

Thalidomide Developed as a sedative in the early 1960s but found to cause a rare birth defect, phocomelia. In 1962 legislation was passed that new drugs must undergo sufficient animal and human testing prior to approval for use by the US FDA. 

This is the way the methods for the scientific study of drugs in humans, the first theme of clinical pharmacology, were developed. The thalidomide disaster of 1961 stimulated the acceptance of the need for scientific evidence of efficacy and safety of drugs before they are marketed and promoted. Requiring this evidence by government agencies before approval for marketing then followed. 

The second catastrophe that influenced the development of medicines regulation far more than any event in history was the thalidomide disaster. Thalidomide was a sedative and hypnotic that first went on sale in Western Germany in 1956. Between 1958 and 1960 it was introduced in 46 different countries worldwide resulting in an estimated 10,000 babies being born with phocomelia and other... 

Neubert R, Neubert D (1997) Peculiarities and possible mode of actions of thalidomide. Chapter 22. Drug toxicity in embryonic development II. In Kavlock RJ, Daston GP (eds) Springer Verlag. The handbook of experimental Pharmacology 124/11, pp 41-119... 

Although the concept of drug-induced teratogenicity was well established at the time thalidomide was being developed, questions remain today as to whether the effects on embryo-fetal development would have been detected using the standard testing methods. 

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