KM11060 is a corrective agent for the F508 deletion (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR), aiming to address the trafficking malfunction associated with this mutation. This compound has applications in researching the F508del-CFTR processing anomaly and contributes to the advancement of cystic fibrosis studies[1].
体内研究
In the context of LPS-induced acute lung inflammation, interventions like PSGL-1 (P-selectin glycoprotein ligand-1) or P-selectin blockade, PAF antagonism with WEB2086, or the amendment of mutated CFTR trafficking with KM11060 significantly elevate plasma lipoxin A4 concentrations in F508del compared to wildtype mice, suggesting potential therapeutic strategies[2].
体外研究
As a small-molecule corrector, KM11060 represents a valuable pharmacological resource for investigating the F508del-CFTR processing defect and for aiding the creation of cystic fibrosis treatments. It enables the recovery of F508del-CFTR trafficking in both cultured cells and native epithelial tissues, offering partial amendment of the F508del-CFTR processing error and augmenting its surface expression to 75% of the levels found in cells treated under low-temperature conditions. With up to 50% of the F508del-CFTR in KM11060-treated cells undergoing complex glycosylation—a process indicative of Golgi apparatus passage—KM11060 stands out as a promising candidate for cystic fibrosis therapeutic development[1].
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