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 Kd of 1.6 μM. MYCMI-6 inhibits tumor cell growth in a MYC-dependent manner (IC50<0.5 μM). MYCMI-6 is not cytotoxic to normal human cells. MYCMI-6 induces apoptosis .
The MYC family of oncogenes, which encodes basic helix-loop-helix leucine zipper (bHLHZip) transcription factors, is considered as one of the most important drivers of tumor development and has been highlighted as a key therapeutic target for cancer therapy for a number of tumor types. MYCMI-6 is a potent and selective inhibitor of MYC:MAX interaction with an IC50 less than 1.5 μM and binds to the MYC bHLHZip domain with a KD of 1.6 ± 0.5 μM. MYCMI-6 significantly reduced growth of the MYCN-amplified cell lines and the MYCN-non-amplified cell lines with average growth inhibition of 50% (GI50) values of 2.5-6 μM and 20 μM, respectively. Further, MYCMI-6 efficiently inhibited anchorage-independent growth of MYCN-amplified neuroblastoma cells with a GI50 value less than 0.4 μM. In vivo, MYCMI-6 (20 mg/kg; i.p.; daily for 1-2 weeks) induced massive apoptosis and reduces tumor cell proliferation, tumor microvasculature density and MYC:MAX interaction in a MYC-dependent xenograft tumor model[2].
作用机制
MYCMI-6 blocks MYC-driven transcription and binds selectively to the MYC bHLHZip domain[2].
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