10074-G5 (413611-93-5) inhibits c-Myc by disrupting c-Myc/Max heterodimer formation and inhibiting its transcriptional activity.1 10074-G5 binds to the c-Myc bHLHZip domain with Kd=2.8 mM.1 It was cytotoxic in C-Myc-overexpressing cell lines (IC50s = 13 to 15 mM) but was not active in vivo due to rapid metabolism.2 10074-G5 is a useful tool to probe for involvement of c-Myc involvement in cellular processes.3,4 Binds to and sequesters the intrinsically disordered amyloid-β (Aβ) in its monomeric soluble state and rescues a C. elegans model of Aβ-associated toxicity.5
References/Citations:
- Follis et al. (2008), Structural rationale for the coupled binding and unfolding of the c-Myc oncoprotein by small molecules; Chem..Biol. 15 1149
- Clausen et al. (2010), In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of 10074-G5, a novel small-molecule inhibitor of c-Myc/Max dimerization; J. Pharmacol. Exp. Ther. 335 715
- Velpula et al. (2012), Transcriptional repression of Mad-Max complex by human umbilical cord blood stem cells downregulates extracellular signal-regulated kinase in glioblastoma; Stem Cells Dev. 21 1779
- Wu et al. (2018), Oxidative stress enhances tumorigenicity and stem-like features via the activation of the Wnt/β-catenin/MYC/Sox2 axis in ALK-positive anaplastic large-cell lymphoma; BMC Cancer 18 361
- Heller et al. (2020), Small-molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer’s disease; Sci. Adv. 6 eabb5924
