ROMK-IN-1

ROMK-IN-1 is an orally active inhibitor of ROMK (Kir1.1) with an IC₅₀ of 0.073 μM. ROMK-IN-1 exhibits no activity against Kir2.1, Kir4.1, Kir7.1, Nav1.5, Cav1.2, as well as the enzymes CYP3A4, CYP2D6, and CYP2C9. ROMK-IN-1 can be used in research related to hypertension^[1]. In Vitro:ROMK-IN-1 (compound 25) potently inhibits ROMK with an IC₅₀ of 0.073 μM, and exhibits 278-fold selectivity over hERG in electrophysiological assays^[1].
ROMK-IN-1 exhibits excellent selectivity for the ROMK ion channel over the Kir2.1, Kir4.1, Kir7.1, Nav1.5, and Cav1.2 ion channels, with IC₅₀ values greater than 30 μM for all tested off-target channels^[1].
ROMK-IN-1 (10 μM) exhibits high selectivity for ROMK in a screening panel comprising 115 off-target enzyme and binding assays, with only the somatostatin receptor subtype 2 being inhibited, showing an IC₅₀ of 4.1 μM^[1].
ROMK-IN-1 (up to 50 μM) exhibits no significant inhibitory effect on CYP3A4, CYP2D6 or CYP2C9 enzymes, with an IC₅₀ value greater than 50 μM^[1].
ROMK-IN-1 (incubated for 45 min) exhibits high microsomal stability in both preclinical species and humans, with 72-89% of the parent drug remaining after 45 min of incubation^[1].
ROMK-IN-1 (incubated for 90 min) exhibits extremely low in vitro metabolic levels in rhesus monkey and human hepatocytes, with 92-99% of the parent drug remaining after 90 min of incubation^[1]. In Vivo:ROMK-IN-1 (compound 25) (3-30 mg/kg; p.o.; once daily for 3 consecutive days) produces a dose-dependent diuretic effect and reduces systolic blood pressure in spontaneously hypertensive rats^[1].
ROMK-IN-1 (intravenous infusion) does not alter the QTc interval in anesthetized guinea pigs at a mean maximum free plasma peak concentration of 83 μM ^[1].