Enhances the Particulate Guanylyl Cyclase Receptor A (pGC-A) to Treat Metabolic Disease, Cardiovascular Disease, and Renal Disease
These organic compounds are effective in treating metabolic, cardiovascular and renal diseases. Cardiovascular diseases are the leading cause of death globally. Hypertension, a common cardiac disease, is the primary risk factor for heart failure, myocardial infarction, sudden cardiac death, chronic kidney disease, stroke, and dementia. Therefore, lowering blood pressure is essential to mitigate the risk of developing severe cardiac disease and to improve outcomes.
The particulate guanylyl cyclase receptor A (pGC-A) is the molecular target of the cardiac hormones atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). The binding of ANP or BNP to pGC-A produces cyclic 3’,5’-guanosine monophosphate (cGMP), involved in physiological functions such as regulation of blood pressure and endocrine and renal functions, as well as cardiovascular protection from obesity. Previous studies have shown that individuals expressing elevated levels of ANP or BNP are at a lower risk for developing hypertension or type II diabetes, respectively, signifying the protective role of pGC-A. Additionally, administration of BNP can reverse cardiac hypertrophy and improve myocardial function in patients. However, although activation of the pGC-A/cGMP pathway depicts an attractive pharmacological target for metabolic, cardiovascular and renal, the rapid clearance of ANP and BNP poses an obstacle to efficiently leveraging its protective functions.
Researchers at the University of Florida have discovered a group of halobenzo[d]thiazole compounds, effective in treating metabolic, cardiovascular and renal diseases. This class of organic compounds increases the responsiveness of the particulate guanylyl cyclase receptor A(pGC-A) to the endogenous ligands ANP and BNP, leading to enhancement of pGC-A activity and increased production of cyclic guanosine monophosphate(cGMP).
Application
Activation of the endogenous pGC-A/cGMP pathway to restore or augment natural levels and treat metabolic disease, cardiovascular disease, and renal disease
Advantages
- These compounds increase pGC-A responsiveness to its endogenous ligands ANP and BNP, even at low levels, enhancing pGC-A function in a positive allosteric manner
- The compounds activate the particulate guanylyl cyclase receptor A (pGC-A)/ cyclic guanosine monophosphate (cGMP) pathway, enhancing protection against obesity, metabolic syndrome, renal and cardiovascular and diseases
- In in vitro studies, the compounds have shown the potential to mediate protection in human cardiomyocytes, renal cells, and adipocytes
Technology
These halobenzo[d]thiazole compounds can effectively treat metabolic, cardiovascular and renal diseases by enhancing the particulate guanylyl cyclase receptor A (pGC-A). pGC-A is the molecular target of the cardiac hormones atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), functioning via the production of cyclic 3’,5’-guanosine monophosphate (cGMP). Production of cGMP after binding the ANP and BNP to pGC-A, results in the regulation of blood pressure, obesity, and cancer, as well as renoprotective and cardioprotective actions. These halobenzo[d]thiazole increase pGC-A responsiveness to ANP and BNP in a positive allosteric fashion, activating the pGC-A/cGMP pathway and increasing cGMP production.
Brochure
