Fibrosis is a common feature of several diseases, involves different organs, and results in significant morbidity and mortality. There are currently no effective therapies to halt the progression of fibrosis or reverse it. We have identified the highly water-soluble MMS-350, a novel bis-oxetanyl sulfoxide, as an antifibrotic agent. MMS-350 reduced the profibrotic phenotype induced in vitro in primary human fibroblasts and ameliorated bleomycin-induced pulmonary fibrosis in vivo. Furthermore, MMS-350 reversed fibrosis in human skin in organ culture. MMS-350 reduced levels of extracellular matrix proteins, the activation of fibroblasts, and the induction of pro-fibrotic factors. Similar effects at lower concentrations were observed with KRL507-031 and CL-613-091, two more lipophilic MMS-350 analogues. The fact that MMS-350 was effective at reducing pulmonary fibrosis induced by different triggers, the differential biological effects of its close structural analogues and its oral availability make it an attractive therapeutic candidate for organ fibrosis.

中文翻译：

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Oxetanyl Suffoxide MMS-350 在体外、体内和体外改善肺纤维化

纤维化是几种疾病的共同特征，涉及不同的器官，并导致显着的发病率和死亡率。目前没有有效的疗法来阻止或逆转纤维化的进展。我们已经确定了高度水溶性的 MMS-350，一种新型的双氧杂环丁烷亚砜，作为一种抗纤维化剂。MMS-350 减少了体外诱导的原代人成纤维细胞的促纤维化表型，并在体内改善了博莱霉素诱导的肺纤维化. 此外，MMS-350 在器官培养中逆转了人体皮肤的纤维化。MMS-350 降低了细胞外基质蛋白的水平、成纤维细胞的活化和促纤维化因子的诱导。使用 KRL507-031 和 CL-613-091 这两种更亲脂的 MMS-350 类似物在较低浓度下观察到类似的效果。MMS-350 可有效减少由不同触发因素引起的肺纤维化，其紧密结构类似物的不同生物学效应及其口服可用性使其成为器官纤维化的有吸引力的治疗候选者。