MYCMI-6 (NSC354961) is a potent and selective endogenous MYC:MAX protein interactions inhibitor. MYCMI-6 blocks MYC-driven transcription and binds selectively to the MYC bHLHZip domain with a K d of 1.6 μM. MYCMI-6 inhibits tumor cell growth in a MYC-dependent manner (IC 50 <0.5 μM). MYCMI-6 is not cytotoxic to normal human cells. MYCMI-6 induces apoptosis.
In Vitro
MYCMI-6 (NSC354961) (6.25?μM; 48 hours) selectively suppresses MYC-driven tumor cell growth with high efficacy. ?\nMYCMI-6 significantly inhibits growth of Burkitt’s lymphoma cells (Mutu, Daudi and ST486) - another classical example of a MYC-driven tumor, having translocations of MYC to one of the immunoglobulin loci - in a dose-dependent manner with an average GI 50 of 0.5?μM. Treatment of MCF7 cells with the MYCMI-6 for 24?hours significantly decreased MYC:MAX isPLA signals to 7%. Titration showed an IC 50 for inhibition of MYC:MAX of less than 1.5?μM for MYCMI-6 by isPLA. MYCMI-6 inhibits the MYC:MAX heterodimer formation with an IC 50 of 3.8?μM. MYCMI-6 efficiently inhibits anchorage-independent growth of MYCN -amplified neuroblastoma cells with GI 50 values of <0.4?μM. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: MYCN -amplified neuroblastoma cells (IMR-32, Kelly and SK-N-DZ), MYCN -non-amplified neuroblastoma cells (SK-N-F1, SK-N-AS and SK-N-RA) Concentration: 6.25 μM Incubation Time: 48 hours Result: Reduced growth of the MYCN -amplified cell lines significantly stronger than the MYCN -non-amplified cell lines.
In Vivo
MYCMI-6 (20?mg/kg; i.p.; daily for 1-2 weeks) induces massive apoptosis and reduces tumor cell proliferation, tumor microvasculature density and MYC:MAX interaction in a MYC-dependent xenograft tumor model . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: 6-8 weeks old athymic nude mice (bearing MYCN-amplified SK-N-DZ neuroblastoma cells) Dosage: 20 mg/kg body weight Administration: I.p.; daily for 1-2 weeks Result: A dramatic increase in the extension of apoptotic areas in the tumors and a significant increase in non-proliferative areas as determined by Ki67 staining in tumors.
