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Ref Type Journal Article
PMID (31679823)
Authors Han H, Jain AD, Truica MI, Izquierdo-Ferrer J, Anker JF, Lysy B, Sagar V, Luan Y, Chalmers ZR, Unno K, Mok H, Vatapalli R, Yoo YA, Rodriguez Y, Kandela I, Parker JB, Chakravarti D, Mishra RK, Schiltz GE, Abdulkadir SA
Title Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy.
Journal Vol Issue Date Pages Journal Short Title
Cancer cell 36 5 2019 Nov 11 483-497.e15 Cancer Cell
URL
Abstract Text Small molecules that directly target MYC and are also well tolerated in vivo will provide invaluable chemical probes and potential anti-cancer therapeutic agents. We developed a series of small-molecule MYC inhibitors that engage MYC inside cells, disrupt MYC/MAX dimers, and impair MYC-driven gene expression. The compounds enhance MYC phosphorylation on threonine-58, consequently increasing proteasome-mediated MYC degradation. The initial lead, MYC inhibitor 361 (MYCi361), suppressed in vivo tumor growth in mice, increased tumor immune cell infiltration, upregulated PD-L1 on tumors, and sensitized tumors to anti-PD1 immunotherapy. However, 361 demonstrated a narrow therapeutic index. An improved analog, MYCi975 showed better tolerability. These findings suggest the potential of small-molecule MYC inhibitors as chemical probes and possible anti-cancer therapeutic agents.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
MYCi975 MYCi975 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
MYCi975 NUCC-0200975 c-MYC Inhibitor 12 MYCi975 is an inhibitor of MYC that blocks the interaction between Myc and Max, which leads to reduced Myc stability, thereby potentially enhancing the antitumor immune response, and inhibiting colony formation and tumor growth (PMID: 31679823).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References