KCC 07

KCC-07 is a potent, selective and brain-penetrant MBD2 (methyl-CpG-binding domain protein 2) inhibitor. KCC-07 prevents binding of MBD2 to methylated DNA and activates brain specific angiogenesis inhibitor 1 (BAI1) inducing anti-proliferative BAI1/p53/p21 signaling. Anticancer activity[1].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA Alkylator/Crosslinker

MBD2 (methyl-CpG-binding domain protein 2)[1]

KCC-07 (10 μM; 72 hours; MB cells) treatment clearly inhibited MB cell growth in vitro, consistent with induction of anti-proliferative BAI1/p53/p21 signaling[1]. KCC-07 (10 μM; 48 hours; MB cells) treatment largely abrogates MBD2 binding to the ADGRB1 promoter and restores BAI1 mRNA and protein expression in BAI1-silent MB cells[1]. Cell Viability Assay[1] Cell Line: Medulloblastomas (MB) cells Concentration: 10 μM Incubation Time: 72 hours Result: Clearly inhibited MB cell growth in vitro. Western Blot Analysis[1] Cell Line: Medulloblastomas (MB) cells Concentration: 10 μM Incubation Time: 48 hours Result: Largely abrogated MBD2 binding to the ADGRB1 promoter in BAI1-silent MB cells.

KCC-07 (100 mg/kg; intraperitoneal injection; 5 days/week; athymic nude mice) treatment inhibits tumor growth and significantly extends the survival of MB xenografts in vivo[1]. Animal Model: Outbred athymic nude mice (females; 8-10 weeks old) injected with MB cells[1] Dosage: 100 mg/kg Administration: Intraperitoneal injection; 5 days/week Result: Significantly extended the survival of MB xenografts in vivo.

[1]. Dan Zhu, et al. BAI1 Suppresses Medulloblastoma Formation by Protecting p53 From Mdm2-Mediated Degradation. Cancer Cell. 2018 Jun 11;33(6):1004-1016.e5.