Cloridarol

Cloridarol is an inhibitor of human islet amyloid polypeptide (hIAPP) that prevents its abnormal misfolding and aggregation. It enhances cell viability, inhibits apoptosis, and protects pancreatic β cells from hIAPP-induced cytotoxicity. Cloridarol is applicable in research related to type 2 diabetes (T2D).

Cloridarol (25-125 µM; 0-20 hours) inhibits hIAPP aggregation in a dose-dependent manner, reducing final fiber formation by up to 55.6%. At 125 µM over 5-24 hours, it alters the morphology of hIAPP aggregates, prevents their secondary structure from transitioning into β-sheet formations, and maintains a random coil structure. Cloridarol at the same concentration (125 µM; 0-25 hours) inhibits aggregation seeded by lag phase and early growth phase assemblies of hIAPP but does not affect equilibrium phase fibrils. Within 24-48 hours at 25-125 µM, Cloridarol protects RIN-m5F cells from hIAPP-induced toxicity, enhancing cell viability and reducing apoptosis. At a concentration of 50 µM for up to 900 minutes, Cloridarol decreases hIAPP 1−37-induced leakage of large unilamellar vesicle (LUV) membranes, correlating with its protective effect against hIAPP toxicity. It binds to the C-terminal β-sheet region of the hIAPP pentamer, disrupting its structure and reducing β-sheet content, thereby inhibiting aggregation.