Novel Antagonists of Angiotensin Type I Receptor to Treat Hypertension
Categories: “Cardiovascular Diseases“
Reference #: 2013-002
Hypertension and associated diseases, including heart attack, stroke, atherosclerosis, and chronic kidney disease remain the number one cause of death throughout the world. In the United States, more than 50% of hypertensive patients do not have their blood pressure well controlled. Suboptimal blood pressure control is, in part, due to poor patient compliance because of the adverse side effects of (e.g., dizziness, headache, cough, and sexual dysfunction) associated with the widely prescribed angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). Another contributing factor is that patients often need more than one medication to achieve target blood pressure.
Researchers at Georgetown University have identified a seven amino acid peptide (PEP7) that suppresses Angiotensin Type I Receptor (AT1) signaling. Surprisingly, the PEP7 peptide had no effect on ANGII induced IP3 production. PEP7, by inhibiting only Erk1/2 signaling downstream of AT1, is the first selective tool and potential therapeutic that alters only one specific pathway of ANGII signaling in vivo. The use of PEP7 has demonstrated efficacy in rodent models of Angiotensin induced hypertension and behavior and may lead to novel therapeutics for attenuating hypertension.
Specific inhibition of a single signaling pathway (Erk 1/2) downstream of AT1 is effective in controlling hypertension with the potential of having fewer side effects.
Stage of Development
Efficacy has been demonstrated in an in vivo rodent model of hypertension
WO2014/151011 entitled “Selective Inhibitor of Angiotensin II” published September 2014.
Kathryn L. Sandberg, Hong Ji, and Jun Liu