Organogermanium compound, Ge-132, forms complexes with adrenaline, ATP and other physiological cis-diol compounds

Living things contains many important cis-diol compounds, and some of these compounds act in cell-to-cell signalling. For example, extracellular ATP is used as a signal of cellular damage, and catecholamines are used as stress signals and stress hormones. These compounds share the elemental structure of cis-diols. Therefore, cis-diol compound signalling is essential for the maintenance of homeostasis.Moreover, these cis-diol compounds are triggers of pain and some other problems. For example, adrenaline, noradrenaline and dopamine are catecholamines. Additionally, the ribose structures of ATP, GTP, and UTP contain cis-diols, and di-phosphates, mono-phosphates and adenosine are all mono-ribonucleic acids, which also contain cis-diols. Moreover, RNA also contains a cis-diol at the 3′-terminal. We investigated the interactions between cis-diol compounds and the organic germanium compound 3-(trihydroxygermyl) propanoic acid, THGPA. Our data demonstrate that ATP-induced calcium influx in normal human epidermal keratinocytes is reduced by THGPA. THGPA is also known as Ge-132; this compound is very stable, and its safety has been confirmed.

Across the world, many medicines that target receptors (e.g., receptor antagonists) are being used. The blocking of signals at the level of the receptor causes side effects that are due to the blocking of the transduction of important signals. Here, we suggest targeting the ligand to maintain cellular function and reduces side effects. This concept could create new avenues of drug-development research that could benefit patients.

Moreover, our findings are specifically related to adrenaline and noradrenaline as stress signals. We expected that the complex formations of these important compounds will have many biological effects. THGPA, a monomer of Ge-132, has been reported many physiological and therapeutic effects, and we believe that these interactions are likely a major contributor to these effects.

There are many subtypes of receptors for ATP, adrenaline, noradrenaline and adenosine. Therefore, the receptor affinities of these cis-diol compounds are likely diverse, which implies these compounds likely have multiple physiological functions. Indeed, THGPA has many interesting effects. Controlling the strength of the interactions of molecules with structures similar to THGPA and ligands may be useful for a new type of health care. Ge-132 has many physiological effects; e.g., the activation of the immune response by Ge-132 has been reported in many studies. The experiments and results presented in this article may represent a breakthrough in novel drug design.