Thalidomide, which caused severe fetal limb malformations in the 1950s, is now a medicine of hope to save cancer patients around the world.
Thalidomide has right-handed and left-handed enantiomers, and only the left-handed type has teratogenicity, which was reported in 1979 by animal experiments by Professor Blasschke of the University of Münster and others.In other words, it is an experimental result that the right-handed type is safe without inducing malformation, and in fact, it has been re-approved all over the world now that thalidomide has been found to be a therapeutic drug for various diseases such as Hansen and AIDS.

 On the other hand, in the 1990s, a new fact was discovered that thalidomide, whether right-handed or left-handed, becomes an equilibrium mixture (racemized) of them in the body.If racemized in the body, it is unlikely that the right-handed type and the left-handed type will give different animal experimental results, which contradicts the report by Professor Blachke et al.This "thalidomide paradox" could not be explained so far.

 Professor Tetsuo Shibata of Nagoya Institute of Technology and others have succeeded in explaining this paradox using the phenomenon of in vivo self-unequalization.
The hypothesis made by Professor Shibata and others is as follows.First, right-handed thalidomide is transformed into an equal mixture (racemic) with left-handed thalidomide in the body, and then further separated into racemate and right-handed thalidomide by self-heterogeneity.Racemics are expelled from the blood due to their extremely low solubility, leaving only safe right-handed thalidomide to be taken up by metabolic pathways.

 Professor Shibata and his colleagues, who repeated experiments based on this hypothesis, also succeeded in confirming that thalidomide causes a self-heterogeneous phenomenon in vivo.This result supports the validity of the report by Professor Blachke et al. And is expected to be a great impetus for the development of safe thalidomide-type drugs.At the same time, when dealing with drugs containing enantiomers, it can be said that the possibility of in vivo self-heterogeneity may occur.

Paper information:[Scientific Reports] Understanding the Thalidomide Chirality in Biological Processes by the Self-disproportionation of Enantiomers

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