title: EMICORON: A multi-targeting G4 ligand with a promising preclinical profile.
abstract: During the last decade, guanine G-rich sequences folding into G-quadruplex (G4) structures have received a lot of attention and their biological role is now a matter of large debate. Rising amounts of experimental evidence have validated several G-rich motifs as molecular targets in cancer treatment. Despite that an increasing number of small molecules has been reported to possess excellent G4 stabilizing properties, none of them has progressed through the drug-development pipeline due to their poor drug-like properties. In this context, the identification of G4 ligands with more favorable pharmacological properties and with a well-defined target activity could be fruitful for anticancer therapy application.
  
  
  
  This manuscript outlines the current state of knowledge regarding EMICORON, a G4-interactive molecule structurally and biologically similar, on the one side, to coronene and, on the other side, to a bay-monosubstituted perylene.
  
  
  
  Overall this work evidences that EMICORON, a new promising G4 ligand, possesses a marked antitumoral activity both standing alone and in combination with chemotherapeutics. Moreover, EMICORON represents a good example of multimodal class of antitumoral drug, able to simultaneously affect multiple targets participating in several distinct signaling pathways, thus simplifying the treatment modalities and improving the selectivity against cancer cells.
  
  
  
  Due to the importance of G4 forming sequences in crucial biological processes participating in tumor progression, their successful targeting with small molecules could represent a very important innovation in the development of effective therapeutic strategies against cancer. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.
authors.affiliation: SAFU, Department of Research, Diagnosis and Innovative Technologies, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Porru
authors.affiliation: Oncogenomic and Epigenetic Unit, Regina Elena National Cancer Institute, Italy. Electronic address: pasquale.zizza@ifo.gov.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Zizza
authors.affiliation: Department of Chemistry, University of Rome "La Sapienza", Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Franceschin
authors.affiliation: SAFU, Department of Research, Diagnosis and Innovative Technologies, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Leonetti
authors.affiliation: Oncogenomic and Epigenetic Unit, Regina Elena National Cancer Institute, Italy. Electronic address: annamaria.biroccio@ifo.gov.it.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Biroccio
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D054856:G-Quadruplexes / Q000187:drug effects*; D006151:Guanosine / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007094:Imides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010880:Piperidines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D016615:Telomere / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; C000610391:EMICORON; D007094:Imides; D008024:Ligands; D010880:Piperidines; D006151:Guanosine
keywords: Colon cancer; Combination therapy; G4 ligand