Compound 21, a new drug in the fight against vascular damage linked to obesity

A study demonstrating the benefits of the new drug Compound 21 has been published in the prestigious journal Clinical Science as a result of research conducted by the Metabolism and Vascular Function Group-  at the Universidad CEU San Pablo led by Dr. Marta Viana, and under the supervision of Drs. Beatriz Somoza and Marta Gil Ortega. The research project was run in collaboration with Dr. Marisol Fernández Alfonso from the Universidad Complutense de Madrid, GESCAMET; Dr. Ulrike Muscha Steckelings from the University of Southern Denmark; Dr. Thomas Unger, from Maastricht University; and Dr. William Boisvert, from the University of Hawaii. It was financed by the Fundación Universitaria San Pablo CEU / Banco Santander and the Ministry of Economy and Competitiveness.

This research shows the complications provoked by a high-fat diet on endothelial angiotensin II type 2 receptor (AT2R) signaling. This receptor, with an important role in the regulation of arterial tone by maintaining the vascular endothelium functionality through the activation of nitric oxide synthesis, exerts its effects through the formation of dimers with the bradykinin type 2 receptor (B2R) and the Mas receptor (MasR). However, obesity interferes in the communication between these receptors, leading to vascular damage.

The treatment with Compound 21 prevents these alterations by promoting the dimerization and signaling of these receptors, thereby increasing nitric oxide availability and preserving endothelial function. "In this sense, this work represents an important progress in the knowledge of new molecular mechanisms that underlie the development of vascular damage associated with obesity," explains Beatriz Somoza, adding that "Compound 21 is an activator of the so-called 'protective arm' of the renin-angiotensin system that could constitute a potential therapeutic tool in the treatment of vascular damage in obese people due to its non-peptide structure and its oral activity”.

Overweight is an important risk factor for the development of cardiovascular diseases - one of the leading causes of death in the world. While obesity treatment has improved in recent years, vascular damage in obese patients is difficult to reverse. The researchers insist that it is therefore necessary to conduct further research on the mechanisms involved in the development of such damage, and to search for more effective drugs.

According to Raquel González-Blázquez and Martín Alcalá, "it is interesting to point out that the vascular effects of Compound 21 are independent of its metabolic effects since no changes in body weight are observed in response to treatment". In addition, Marta Gil Ortega states, "the study also shows that Compound 21 can contribute both to identifying new therapeutic targets and to the design of new effective drugs in the treatment/prevention of vascular disorders observed in obesity".

Compound 21 has been recognized as an orphan drug - a type of drug aimed at treating rare diseases that is not widely developed by the pharmaceutical industry for economic reasons, but which meets public health needs – for the treatment of idiopathic pulmonary fibrosis, either by European regulatory authorities and by those of the United States. Furthermore, it is currently being tested for the treatment of COVID-19 in a Phase III clinical trial. 

  • Palabras clave
  • Compound 21
  • Drug
  • Obesity
  • Vascular damage
  • Clinical Science


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