Direct modulation of gene expression by targeting oncogenic transcription factors is a new area of research for cancer treatment. ERG, an ETS-family transcription factor, is commonly over-expressed or translocated in leukaemia and prostate carcinoma. In this work, we selected the di-(thiophene-phenyl-amidine) compound DB1255 as an ERG/DNA binding inhibitor using a screening test of synthetic inhibitors of the ERG/DNA interaction followed by electrophoretic mobility shift assays (EMSA) validation. Spectrometry, footprint and biosensor-surface plasmon resonance analyses of the DB1255/DNA interaction evidenced sequence selectivity and groove binding as dimer. Additional EMSA evidenced the precise DNA-binding sequence required for optimal DB1255/DNA binding and thus for an efficient ERG/DNA complex inhibition. We further highlighted the structure activity relationships from comparison with derivatives. In cellulo luciferase assay confirmed this modulation both with the constructed optimal sequences and the Osteopontin promoter known to be regulated by ERG and which ERG-binding site was protected from DNaseI digestion on binding of DB1255. These data showed for the first time the ERG/DNA complex modulation, both in vitro and in cells, by a heterocyclic diamidine that specifically targets a portion of the ERG DNA recognition site.

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A systematic calculation of alpha decay half-lives of 347 nuclei is considered in the framework of the Wentzel–Kramers–Brillouin (WKB) approximation using two formulas. A recently proposed barrier penetration formula, with some modified parameters, is used first. Second, a new analytic barrier penetration formula is derived by taking into account the centrifugal potential. A good agreement with experimental data is achieved especially for spherical nuclei. The new formula reproduces experimental alpha decay half-lives with a satisfying accuracy especially for penetration energies much lower than the Coulomb barrier.

Based on the calculations of the shell and the residual pairing correction energies in the framework of Strutinskyʼs approach, we evaluated the proton and neutron magic numbers in the range 72 Z 282 and 96 N 540. New magic numbers and new islands of stability lie in a range defined by Greenʼs formula and the two-neutrons drip lines are presented. Our calculations reproduced known spherical double-magic nuclei and present evidences on new spherical double-magic nuclei in super-and ultraheavy regions.