Metolazone
UPR activator and longevity inducer / Activates mitochondrial unfolded protein response (UPRMT) and -increases C. elegans lifespan.4 Clinically useful diuretic that inhibits the thiazide-sensitive Na+-Cl– cotransporter (NCC) (IC50 = 0.3 µM rat), blocking sodium reabsorption.2,3 Metolazone also inhibits human carbonic anhydrase isoforms VII, XII, and XIII with nanomolar potency.4.
Biochemicals & reagents
17560-51-9
SR 720-22
Ito et al. (2021), Metolazone upregulates mitochondrial chaperones and extends lifespan in Caenorhabditis elegans; Biogerontology, 22 119 Beaumont et al. (1988), Thiazide diuretic drug receptors in rat kidney: identification with [3H] metolazone; Proc. Natl. Acad. Sci. USA, 85 2311 Moreno et al. (2006), Affinity-defining domains in the Na-Cl cotransporter: a different location for Cl- and thiazide binding; J. Biol. Chem., 281 17266 Temperini et al. (2008), Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for the indapamide-isozyme II adduct; Bioorg. Med. Chem. Lett., 18 2567
RT
TARGET: UPR (Unfolded protein response) -- PATHWAY: Mitochondrial function -- RESEARCH AREA: Cellular stress -- DISEASE AREA: Heart disease; AgeingKidney disease; Hypertension