EMICORON: A multi-targeting G4 ligand with a promising preclinical profile
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...
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| Vydané v: | Biochimica et biophysica acta. General subjects Ročník 1861; číslo 5; s. 1362 - 1370 |
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| Hlavní autori: | , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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Netherlands
Elsevier B.V
01.05.2017
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| ISSN: | 0304-4165, 1872-8006 |
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| 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.
•EMICORON selectively binds and stabilizes G4 structures interspersed in the genome.•EMICORON exerts a potent antitumoral activity.•EMICORON potentiates the efficacy of chemotherapeutics in preclinical studies.•EMICORON represents a valid example of multimodal class of antitumoral drugs. |
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| AbstractList | 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. 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. •EMICORON selectively binds and stabilizes G4 structures interspersed in the genome.•EMICORON exerts a potent antitumoral activity.•EMICORON potentiates the efficacy of chemotherapeutics in preclinical studies.•EMICORON represents a valid example of multimodal class of antitumoral drugs. 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. BACKGROUNDDuring 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.SCOPE OF REVIEWThis 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.MAJOR CONCLUSIONSOverall 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.GENERAL SIGNIFICANCEDue 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. |
| Author | Biroccio, Annamaria Zizza, Pasquale Porru, Manuela Leonetti, Carlo Franceschin, Marco |
| Author_xml | – sequence: 1 givenname: Manuela surname: Porru fullname: Porru, Manuela organization: SAFU, Department of Research, Diagnosis and Innovative Technologies, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy – sequence: 2 givenname: Pasquale surname: Zizza fullname: Zizza, Pasquale email: pasquale.zizza@ifo.gov.it organization: Oncogenomic and Epigenetic Unit, Regina Elena National Cancer Institute, Italy – sequence: 3 givenname: Marco surname: Franceschin fullname: Franceschin, Marco organization: Department of Chemistry, University of Rome “La Sapienza”, Rome, Italy – sequence: 4 givenname: Carlo surname: Leonetti fullname: Leonetti, Carlo organization: SAFU, Department of Research, Diagnosis and Innovative Technologies, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy – sequence: 5 givenname: Annamaria surname: Biroccio fullname: Biroccio, Annamaria email: annamaria.biroccio@ifo.gov.it organization: Oncogenomic and Epigenetic Unit, Regina Elena National Cancer Institute, Italy |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27838395$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1093_nar_gkab952 crossref_primary_10_3390_biomedicines11030969 crossref_primary_10_1093_gastro_goaa022 crossref_primary_10_1016_j_dyepig_2022_110557 crossref_primary_10_1186_s13046_017_0657_3 crossref_primary_10_3390_scipharm93010006 crossref_primary_10_3390_molecules25225407 crossref_primary_10_3390_genes10121030 crossref_primary_10_3390_cancers13246233 crossref_primary_10_1093_nar_gkz095 crossref_primary_10_3748_wjg_v26_i35_5223 crossref_primary_10_1016_j_bbagen_2017_03_022 crossref_primary_10_3390_cancers12071830 crossref_primary_10_4155_fmc_2023_0202 crossref_primary_10_1186_s13046_018_0719_1 |
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| Keywords | G4 ligand Colon cancer TIFs CRC PDX CI TWI MTD Combination therapy G4 MTS GEMM |
| Language | English |
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| Snippet | 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... BACKGROUNDDuring the last decade, guanine G-rich sequences folding into G-quadruplex (G4) structures have received a lot of attention and their biological role... |
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| SubjectTerms | Animals Antineoplastic Agents - chemical synthesis Antineoplastic Agents - metabolism Antineoplastic Agents - pharmacology Antineoplastic Combined Chemotherapy Protocols - pharmacology Binding Sites Cell Proliferation - drug effects Colon cancer Combination therapy DNA, Neoplasm - chemistry DNA, Neoplasm - drug effects DNA, Neoplasm - genetics DNA, Neoplasm - metabolism Drug Design drugs G-Quadruplexes - drug effects G4 ligand guanine Guanosine - chemistry Guanosine - metabolism Humans Imides - chemical synthesis Imides - metabolism Imides - pharmacology Ligands medicinal properties Models, Molecular neoplasms Neoplasms - drug therapy Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology Piperidines - chemical synthesis Piperidines - metabolism Piperidines - pharmacology signal transduction Signal Transduction - drug effects Structure-Activity Relationship Telomere - chemistry Telomere - drug effects Telomere - metabolism therapeutics Tumor Burden - drug effects |
| Title | EMICORON: A multi-targeting G4 ligand with a promising preclinical profile |
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