TD52 dihydrochloride (TD52 2HCl), a derivative of Erlotinib, is a potent and orally active inhibitor of protein phosphatase 2A (CIP2A). It exhibits strong anti-cancer properties by regulating the CIP2A/PP2A/p-Akt signaling pathway, resulting in the induction of apoptosis in triple-negative breast cancer (TNBC) cells. Mechanistically, TD52 dihydrochloride disrupts the binding of Elk1 to the CIP2A promoter, effectively reducing CIP2A levels. Notably, TD52 dihydrochloride demonstrates powerful anti-cancer activity while displaying less inhibition of p-EGFR.

TD52 dihydrochloride（2-10 µM；48小时）展示了抗增殖能力，并在这些细胞系中诱导不同的凋亡效应。TD52二氯化物（5 μM；48小时）对p-EGFR或EGFR表达的影响最小，但会下调CIP2A的表达。TD52 dihydrochloride（2.5、5、7.5 μM；48小时）随时间增长依赖性地诱导凋亡，并伴随着CIP2A和p-Akt的下调。TD52 dihydrochloride（5 μM；24小时）在TNBC细胞中显著增加PP2A的磷酸酶活性。TD52 dihydrochloride（5 μM；48小时）对其他常见的RTKs，如IGFR、PDGFR和VEGFR2没有明显效果[1]。

TD52 dihydrochloride (10 mg/kg/day; oral gavage; for 52 days) significantly inhibits MDA-MB-468 xenograft tumour size and tumour weight[1].