MAS1L Inhibitors

Chemical inhibitors of MAS1L can employ various mechanisms to attenuate the protein's functional activity, primarily by targeting the renin-angiotensin system (RAS), which is closely associated with MAS1L's physiological roles. Losartan, Telmisartan, Candesartan, Eprosartan, Valsartan, Olmesartan, Irbesartan, Azilsartan, Fimasartan, and Saprisartan are angiotensin II type 1 (AT1) receptor antagonists. By blocking the AT1 receptor, these inhibitors prevent the binding of angiotensin II, a peptide hormone that plays a crucial role in vasoconstriction and blood pressure regulation. As a result, the expected downstream signaling cascade, which may involve MAS1L, is reduced, leading to a decrease in the functional consequences that MAS1L might otherwise mediate. Among the AT1 receptor antagonists, each exhibits a similar method of action yet with differing affinities and selectivities, which accounts for the nuances in their capacity to inhibit the potential MAS1L-related pathways.

Aliskiren directly inhibits renin, thereby reducing the conversion of angiotensinogen to angiotensin I and ultimately decreasing the amount of angiotensin II available to interact with receptors that could engage MAS1L. Similarly, PD123319 is a selective inhibitor of the angiotensin II type 2 (AT2) receptor. Although the role of AT2 is less well-defined compared to AT1, its inhibition can influence the balance of angiotensin II effects. The inhibition of AT2 receptor by PD123319 may lead to an alteration in the RAS that can indirectly result in reduced MAS1L signaling due to a shift in angiotensin II's receptor interactions. Collectively, these chemical inhibitors, by modulating the RAS, contribute to the inhibition of MAS1L's activity by limiting its possible engagement in angiotensin-mediated physiological responses.