| Description |
TD52, an Erlotinib (HY-50896) derivative, is an orally active, potent cancerous inhibitor of protein phosphatase 2A (CIP2A) inhibitor. TD52 mediates the apoptotic effect in triple-negative breast cancer (TNBC) cells via regulating the CIP2A/PP2A/p-Akt signalling pathway. TD52 indirectly reduced CIP2A by disturbing Elk1 binding to the CIP2A promoter. TD52 has less p-EGFR inhibition and has potent anti-cancer activity[1].
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| Related Catalog |
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| Target |
Akt
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| In Vitro |
TD52 (2-10 μM; 48 hours) shows anti-proliferative ability and induces differential apoptotic effects in these cell lines[1]. TD52 (5 μM; 48 hours) has minimal effects on p-EGFR or EGFR expression but downregulated CIP2A expression[1]. TD52 (2.5, 5, 7.5 μM; 48 hours) time-dependently induces apoptosis accompanied with downregulating CIP2A and p-Akt[1]. TD52 (5 μM; 24 hours) significantly increases the phosphatase activity of PP2A in TNBC cells[1]. TD52 (5 μM; 48 hours) has no obvious effects on other common RTKs, such as IGFR, PDGFR and VEGFR2[1]. Apoptosis Analysis[1] Cell Line: Three TNBC cell lines including HCC-1937, MDA-MB-231 and MDA-MB-468 cells Concentration: 2, 4, 6, 8, 10 μM Incubation Time: 48 hours Result: Showed anti-proliferative ability and induced differential apoptotic effects in these cell lines. Western Blot Analysis[1] Cell Line: MDA-MB-231 cell Concentration: 5 μM Incubation Time: 48 hours Result: Had minimal effects on p-EGFR or EGFR expression but downregulated CIP2A expression.
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| In Vivo |
TD52 (10 mg/kg/day; oral gavage; for 52 days) significantly inhibits MDA-MB-468 xenograft tumour size and tumour weight[1]. Animal Model: Female NCr athymic nude mice (5-7 weeks of age)[1] Dosage: 10 mg/kg Administration: Oral gavage; daily; for 52 days Result: Significantly inhibits MDA-MB-468 xenograft tumour size and tumour weight. Decreased the protein expressions of CIP2A and p-Akt in the three MDA-MB-468 xenograft tumours.
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| References |
[1]. Chun-Yu Liu, et al. EGFR-independent Elk1/CIP2A signalling mediates apoptotic effect of an erlotinib derivative TD52 in triple-negative breast cancer cells. Eur J Cancer. 2017 Feb;72:112-123.
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