Baxdrostat

At the molecular level, baxdrostat works by selectively targeting and inhibiting the enzyme aldosterone synthase, which is encoded by the CYP11B2 gene and expressed heavily within the adrenal zona glomerulosa. Aldosterone synthase catalyzes the final rate-limiting steps of aldosterone biosynthesis, converting 11-deoxycorticosterone into aldosterone through successive oxidation reactions. By blocking this specific target, baxdrostat effectively prevents the synthesis of aldosterone, reducing the circulating hormone levels that would normally bind to downstream mineralocorticoid receptors (MR). The direct cellular and physiological effect of this inhibition is a significant decrease in the expression of epithelial sodium channels (ENaC) and sodium-potassium ATPase pumps within the plasma membranes of the renal collecting ducts. Consequently, this reduces the passive reabsorption of sodium and the osmotic flow of water back into the bloodstream, successfully preventing fluid retention and lowering systemic blood pressure. Because of its precise molecular structure, baxdrostat avoids steric clashing or interaction with 11β-hydroxylase, a near-identical paralog enzyme encoded by CYP11B1 that is strictly required for cortisol synthesis, thereby maintaining normal adrenocorticotropic hormone-induced cortisol responses. Furthermore, this upstream mechanism effectively circumvents the pathophysiological phenomenon known as "aldosterone escape," which typically causes a paradoxical return of aldosterone secretion during chronic downstream renin-angiotensin-aldosterone system (RAAS) blockade.