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.

The work of discovery of Cisd2 activators targeting NAFLD/NASH is entirely based on the original findings of our team and therefore, is highly innovative. The identified Cisd2 activator has no detectable toxicity in vivo, can activate Cisd2 in liver and ameliorate obese-related and fructose-induced NAFLD/NASH. Our results revealed that the beneficial effects are mainly dependent on a molecular mechanism/pathway involving Cisd2.

NAFLD and its more severe form NASH are a significant threat to global health. Currently no approved therapies specifically for NAFLD or NASH; therefore, the need to find appropriate therapeutics is urgent. In view of the efficacy and safety observed, the development of highly innovative Cisd2 activators may offer a glimmer of hope for patients with NAFLD/NASH. The potential market for NASH medications is forecast to be as large as USD 35 billion per year. We believe that Cisd2 activators will have a place in the field of NAFLD/NASH because of their uniqueness, novelty, and necessity.

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