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Series GSE197062 Query DataSets for GSE197062
Status Public on Mar 08, 2023
Title MYCMI-7 - a small MYC-binding compound that inhibits MYC:MAX interaction and tumor growth in a MYC-dependent manner
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Deregulated expression of MYC family oncogenes occurs frequently in human cancer and is often associated with aggressive disease and poor prognosis. While MYC is a highly warranted target, it has been considered “undruggable”, and no specific anti-MYC drugs are available in the clinic. We recently identified molecules named MYCMIs that inhibit the interaction between MYC and its essential partner MAX. Here we show that one of these, MYCMI-7, efficiently and selectively inhibits MYC:MAX and MYCN:MAX interactions in cells, binds directly to recombinant MYC and reduces MYC-driven transcription. In addition, MYCMI-7 induces degradation of MYC and MYCN proteins. MYCMI-7 potently induces growth arrest/apoptosis in tumor cells in a MYC/MYCN- dependent manner and downregulates the MYC pathway on a global level as determined by RNA-seq. Sensitivity to MYCMI-7 correlates with MYC expression in a panel of 60 tumor cell lines and MYCMI-7 shows high efficacy towards a collection of patient- derived primary glioblastoma and acute myeloid leukemia (AML) ex vivo cultures. Importantly, a variety of normal cells become G1 arrested without signs of apoptosis upon MYCMI-7 treatment. Finally, in mouse tumor models of MYC-driven AML, breast cancer and MYCN-amplified neuroblastoma, treatment with MYCMI-7 downregulates MYC/MYCN, inhibits tumor growth and prolongs survival through apoptosis with little side effects. In conclusion, MYCMI-7 is a potent and selective MYC inhibitor that is highly relevant for the development into clinically useful drugs for treatment of MYC-driven cancer.
 
Overall design RNA-seq of MCF7 breast carcinoma cells treated with either 5 uM MYCMI-7 (n = 2) or DMSO (n = 2) for 24 hrs. MYCMI-7: (2-(5,11-Dimethyl-6H-25-pyrido[4,3-b]carbazol-2-yl)-N,N-diethylethanamine acetate, NSC-359449).
 
Contributor(s) Larsson L, Castell A, Olsen TK
Citation(s) 36874405
Submission date Feb 20, 2022
Last update date Mar 08, 2023
Contact name Lars-Gunnar Larsson
E-mail(s) Lars-Gunnar.Larsson@ki.se
Phone +46 8 52487239
Organization name Karolinska Institute
Department Microbiology, Tumor and Cell Biology
Street address Solnavagen 9
City Stockholm
ZIP/Postal code 75165
Country Sweden
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (4)
GSM5907762 MCF-7 cells treated with MYCMI-7, mycmi_1
GSM5907763 MCF-7 cells treated with MYCMI-7, mycmi_2
GSM5907764 MCF-7 cells treated with DMSO, dmso_3
Relations
BioProject PRJNA808742

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Supplementary file Size Download File type/resource
GSE197062_counts.csv.gz 235.6 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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