MYCMI-7 hydrobromide is a potent and selective MYC/MYCN inhibitor, with a K d of 4 μM for MYC and an IC50 of 10 μM for topoisomerase IIα ( Topoisomerase II α ). MYCMI-7 hydrobromide binds directly to MYC, selectively inhibits the interactions of MYC:MAX and MYCN:MAX, reduces MYC -driven transcription levels, induces MYC / MYCN protein degradation, and blocks the binding of MYC to chromatin, thereby inducing tumor cell growth arrest, apoptosis and reducing cell viability, while only inducing G1 phase growth arrest in normal cells. MYCMI-7 hydrobromide can be used in research related to MYC -driven acute myeloid leukemia and breast cancer, MYCN -amplified neuroblastoma, glioblastoma, Burkitt's lymphoma, melanoma, colon cancer, osteosarcoma, cervical cancer and histiocytic lymphoma [1].
In Vivo, MYCMI-7 (12.5 mg/kg; i.p.; once daily; 15 days) hydrobromide reduces tumor burden, downregulates MYC expression, and induces markers of apoptosis and senescence in MYC-driven AML mouse models[1]. MYCMI-7 (6.25 mg/kg; i.t.; twice weekly; 26 days) hydrobromid einhibits the growth of MDA-MB-231 breast cancer xenografts, reduces MYC expression levels, induces cell apoptosis, and significantly improves the survival rate of mice[1]. MYCMI-7 (6.25 mg/kg; i.t.; twice weekly; 20 days) hydrobromide inhibits the growth of MYCN-amplified SK-N-DZ neuroblastoma xenografts, reduces MYCN expression, and significantly improves the survival rate of mice[1].
In Vitro, MYCMI-7 hydrobromide (0.5-10 μM; 72 h) induces growth arrest in normal human skin fibroblasts without reducing cell viability[1]. MYCMI-7 hydrobromide (1-100 μM; 10 min) potently inhibits the decatenation activity of recombinant human Top2α in cell-free assays[1]. MYCMI-7 hydrobromide (5 μM; 6 h) blocks the binding of MYC to the promoter of the ODC1 target gene in U-937 cells[1]. MYCMI-7 (1-6 h) hydrobromide reduces the formation of MYC:MAX complex and the expression of MYC protein in MCF7 cells in a time-dependent manner[1]. MYCMI-7 hydrobromide (5 μM; 17 h) downregulates the protein expression of MYC, MYCN, phosphorylated MYC, and MAX in MCF7, HeLa, Kelly, P493-6, HCT116, and neuroblastoma cell lines, and reduces the steady-state levels of wild-type and mutant MYC in U2OS cells[1]. MYCMI-7 (10-30 μM; 96 h) hydrobromide reduces the growth of H015.19 Rat1 fibroblasts in a concentration-dependent manner[1]. MYCMI-7 (0.1-6.25 μM; 2 h-2 weeks) hydrobromide inhibits anchorage-independent growth of SK-N-DZ MYCN-amplified neuroblastoma cells, potently reduces the growth capacity of MYC-translocated Daudi, Raji and Mutu Burkitt lymphoma cells after 24 hours, and strongly decreases anchorage-independent colony formation of MYC+HRAS-transformed primary REF[1]. MYCMI-7 hydrobromide reduces the growth of MDA-MB-231 cells with a GI50 of approximately 5.5-5.8 μM, and knockdown of Top2α does not alter the sensitivity of cells to MYCMI-7[1]. MYCMI-7 (0.5-12 μM; 72 h) hydrobromide potently inhibits the growth/activity of AML cells driven by MYC/BCL-XL, and suppresses the growth of MDA-MB-231 breast cancer cells in a concentration-dependent manner[1].
References:
[1]. Castell A, et al. MYCMI-7: A Small MYC-Binding Compound that Inhibits MYC: MAX Interaction and Tumor Growth in a MYC-Dependent Manner. Cancer research communications. 2022 Mar;2(3):182-201.
In Vivo, MYCMI-7 (12.5 mg/kg; i.p.; once daily; 15 days) hydrobromide reduces tumor burden, downregulates MYC expression, and induces markers of apoptosis and senescence in MYC-driven AML mouse models[1]. MYCMI-7 (6.25 mg/kg; i.t.; twice weekly; 26 days) hydrobromid einhibits the growth of MDA-MB-231 breast cancer xenografts, reduces MYC expression levels, induces cell apoptosis, and significantly improves the survival rate of mice[1]. MYCMI-7 (6.25 mg/kg; i.t.; twice weekly; 20 days) hydrobromide inhibits the growth of MYCN-amplified SK-N-DZ neuroblastoma xenografts, reduces MYCN expression, and significantly improves the survival rate of mice[1].
In Vitro, MYCMI-7 hydrobromide (0.5-10 μM; 72 h) induces growth arrest in normal human skin fibroblasts without reducing cell viability[1]. MYCMI-7 hydrobromide (1-100 μM; 10 min) potently inhibits the decatenation activity of recombinant human Top2α in cell-free assays[1]. MYCMI-7 hydrobromide (5 μM; 6 h) blocks the binding of MYC to the promoter of the ODC1 target gene in U-937 cells[1]. MYCMI-7 (1-6 h) hydrobromide reduces the formation of MYC:MAX complex and the expression of MYC protein in MCF7 cells in a time-dependent manner[1]. MYCMI-7 hydrobromide (5 μM; 17 h) downregulates the protein expression of MYC, MYCN, phosphorylated MYC, and MAX in MCF7, HeLa, Kelly, P493-6, HCT116, and neuroblastoma cell lines, and reduces the steady-state levels of wild-type and mutant MYC in U2OS cells[1]. MYCMI-7 (10-30 μM; 96 h) hydrobromide reduces the growth of H015.19 Rat1 fibroblasts in a concentration-dependent manner[1]. MYCMI-7 (0.1-6.25 μM; 2 h-2 weeks) hydrobromide inhibits anchorage-independent growth of SK-N-DZ MYCN-amplified neuroblastoma cells, potently reduces the growth capacity of MYC-translocated Daudi, Raji and Mutu Burkitt lymphoma cells after 24 hours, and strongly decreases anchorage-independent colony formation of MYC+HRAS-transformed primary REF[1]. MYCMI-7 hydrobromide reduces the growth of MDA-MB-231 cells with a GI50 of approximately 5.5-5.8 μM, and knockdown of Top2α does not alter the sensitivity of cells to MYCMI-7[1]. MYCMI-7 (0.5-12 μM; 72 h) hydrobromide potently inhibits the growth/activity of AML cells driven by MYC/BCL-XL, and suppresses the growth of MDA-MB-231 breast cancer cells in a concentration-dependent manner[1].
References:
[1]. Castell A, et al. MYCMI-7: A Small MYC-Binding Compound that Inhibits MYC: MAX Interaction and Tumor Growth in a MYC-Dependent Manner. Cancer research communications. 2022 Mar;2(3):182-201.