Runcaciguat

Runcaciguat (BAY 1101042) is a selective, orally active, allosteric activator of soluble guanylate cyclase (sGC) that specifically targets its oxidized and heme-free form. Runcaciguat binds to sGC in a histidine-dependent manner and restores cyclic guanosine monophosphate (cGMP) production under oxidative stress, independent of nitric oxide (NO) or heme. Runcaciguat exhibits renoprotective and cardioprotective activities, such as reduced proteinuria and improved renal function. Runcaciguat is primarily being studied in chronic kidney disease (CKD) associated with hypertension, diabetes, and metabolic disorders, as well as potential cardiovascular indications such as heart failure with preserved ejection fraction (HFpEF)^[1][2][3]. In Vitro:Runcaciguat (100 pM-10 μM; 10 min) activates wild-type soluble guanylate cyclase (sGC, EC₅₀=789 nM) in HEK293 cells, but inactive against the β₁H105A/F mutant, confirming that its activation is dependent on the histidine 105 residue of the β₁ subunit^[1]. In Vivo:Runcaciguat (1-10 mg/kg; oral gavage or mixed feed; 1-2 times a day; 2-12 weeks) significantly reduces proteinuria, improves renal function markers (such as Cyst-C, KIM-1), alleviates renal pathological damage (such as glomerular sclerosis, tubular degeneration) in chronic kidney disease (CKD) models such as ANG-SD rats, RenTG rats, ZDF rats and ZSF1 rats, and improves the survival rate of RenTG rats^[2][3].