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F-HSA-LDP-AE is a novel folate receptor (FR)-directed, macropinocytosis-enhanced bioconjugate designed for the treatment of pancreatic cancer, particularly K-Ras mutant pancreatic ductal adenocarcinoma (PDAC). The molecule is composed of four functional moieties: folate (F) for receptor targeting, human serum albumin (HSA) to exploit the high macropinocytic activity of K-Ras mutant cells and improve pharmacokinetics, the apoprotein of lidamycin (LDP), and the active enediyne (AE) chromophore. This bioconjugate demonstrates potent cytotoxicity by inducing G2/M cell cycle arrest and apoptosis through DNA damage. Preclinical studies have shown significant tumor growth inhibition in pancreatic cancer xenograft models at well-tolerated doses.
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