443290-10-6Relevant articles and documents
A structure—activity relationship study of bis-benzamides as inhibitors of androgen receptor—coactivator interaction
Lee, Tae-Kyung,Ravindranathan, Preethi,Sonavane, Rajni,Raj, Ganesh V.,Ahn, Jung-Mo
, (2019/08/07)
The interaction between androgen receptor (AR) and coactivator proteins plays a critical role in AR-mediated prostate cancer (PCa) cell growth, thus its inhibition is emerging as a promising strategy for PCa treatment. To develop potent inhibitors of the
Perturbation of the c-Myc-Max Protein-Protein Interaction via Synthetic α-Helix Mimetics
Jung, Kwan-Young,Wang, Huabo,Teriete, Peter,Yap, Jeremy L.,Chen, Lijia,Lanning, Maryanna E.,Hu, Angela,Lambert, Lester J.,Holien, Toril,Sundan, Anders,Cosford, Nicholas D. P.,Prochownik, Edward V.,Fletcher, Steven
, p. 3002 - 3024 (2015/04/27)
The rational design of inhibitors of the bHLH-ZIP oncoprotein c-Myc is hampered by a lack of structure in its monomeric state. We describe herein the design of novel, low-molecular-weight, synthetic α-helix mimetics that recognize helical c-Myc in its transcriptionally active coiled-coil structure in association with its obligate bHLH-ZIP partner Max. These compounds perturb the heterodimer's binding to its canonical E-box DNA sequence without causing protein-protein dissociation, heralding a new mechanistic class of "direct" c-Myc inhibitors. In addition to electrophoretic mobility shift assays, this model was corroborated by further biophysical methods, including NMR spectroscopy and surface plasmon resonance. Several compounds demonstrated a 2-fold or greater selectivity for c-Myc-Max heterodimers over Max-Max homodimers with IC50 values as low as 5.6 μM. Finally, these compounds inhibited the proliferation of c-Myc-expressing cell lines in a concentration-dependent manner that correlated with the loss of expression of a c-Myc-dependent reporter plasmid despite the fact that c-Myc-Max heterodimers remained intact. (Chemical Equation Presented).
