Our previous studies suggested that increase Cisd2 levels may attenuate the pathogenesis of NAFLD/NASH. Accordingly, potent Cisd2 activators with the capacity to enhance Cisd2 levels were identified through the screening of skeletally diverse collections and structural optimization. So far BPRCD0001S0 is the most potent Cisd2 activator obtained, which has been studied extensively. Data obtained revealed that BPRCD0001S0 has no detectable toxicity in vivo, can activate Cisd2 in liver and ameliorate obese-related and fructose-induced NAFLD/NASH.