https://doi.org/10.4081/bse.178
Innovative 3D proteome-wide scale identification of ALKBH5 target for MV1035 small molecule able to reduce migration and invasiveness in U87 glioblastoma cell lines by SPILLO-PBSS
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
The innovative in silico technologies developed at SPILLOproject,1 e.g., the SPILLO potential binding sites searcher (SPILLO-PBSS) software,2,3 allow to identify targets and off-targets of any small molecule on a multiple-organism proteomewide scale, and to perform an accurate multilevel cross-organism transferability analysis (MCOTA) aimed at rationalising animal testing. SPILLO-PBSS has been successfully used in several research projects, such as a study in which a compound (MV1035) was found to reduce migration and invasiveness in U87 glioblastoma (GBM) cell lines: the human structural proteome was analyzed and the RNA demethylase ALKBH5 has been identified as a target responsible for the observed effects (target experimentally validated). Another top-ranked target identified by SPILLO-PBSS, the DNA repair protein AlkB homolog 2 (ALKBH2), abundantly expressed in GBM cell lines, resulted particularly interesting for its pivotal role in the onset of resistance to Temozolomide (TMZ), the standard firstline treatment for GBM.2
2. Malacrida A, Rivara M, Di Domizio A, Cislaghi G, Miloso M, Zuliani V, Nicolini G. 3D proteome-wide scale screening and activity evaluation of a new ALKBH5 inhibitor in U87 glioblastoma cell line. Bioorg Med Chem 2020;28:115300.
3. Di Domizio A, Vitriolo A, Vistoli G, Pedretti A. SPILLO-PBSS: detecting hidden binding sites within protein 3D-structures through a flexible structure-based approach. J Comput Chem 2014;35:2005-17.
4. Giatti S, Di Domizio A, Diviccaro S, et al. Three-dimensional proteome-wide scale screening for the 5-alpha reductase inhibitor finasteride: identification of a novel off-target. J Med Chem 2021;64:4553-66.
How to Cite
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Maria Sampieri, Riccardo Villa, Silvia Dotti, Zebrafish as an alternative method for toxicological studies , Biomedical Science and Engineering: Vol. 1 No. 1 (2020)
- Sara Tirendi, Stefania Vernazza, Sergio Saccà, Anna Maria Bassi, Assessment of an in vitro physiological relevant model to check therapeutic strategies for glaucoma , Biomedical Science and Engineering: Vol. 1 No. 1 (2020)
- Massimiliano Runfola, Michele Perni, Simona Sestito, Grazia Chiellini, Michele Vendruscolo, Simona Rapposelli, SG-2: A promising lipolytic and pro-autophagic hit-compound to treat Alzheimer's disease , Biomedical Science and Engineering: Vol. 1 No. 1 (2020)
- Salvatore Simmini, Allen C. Eaves, Sharon A. Louis, Wing Chang, Human pluripotent stem cell-derived organoids and their potential to reduce the use of animal models in research , Biomedical Science and Engineering: Vol. 3 No. 1 (2022)
- Alessandra Aldieri, Mara Terzini, Diana Massai, Cristina Bignardi, Alberto Audenino, Development of an animal-free methodology for mechanical performance assessment of engineered skin substitutes , Biomedical Science and Engineering: Vol. 1 No. 1 (2020)
- Claudio Conci, Emanuela Jacchetti, Tommaso Zandrini, Laura Sironi, Maddalena Collini, Giuseppe Chirico, Giulio Cerullo, Roberto Osellame, Manuela Teresa Raimondi, Quantification of the foreign body reaction by means of a miniaturized imaging window for intravital nonlinear microscopy , Biomedical Science and Engineering: Vol. 1 No. 1 (2020)
- Paola Petrini, Daniela Pacheco, Francesco Briatico Vangosa, Cosmin S. Butnarasu, Livia Visai, Orietta Monticelli, Laura Pastorino, Sonja Visentin, Hydrogel-based platforms to mimic in vivo drug diffusion: A multicenter research , Biomedical Science and Engineering: Vol. 1 No. 1 (2020)
- Flaminia Aliberti, Lorenza Rinvenuto, Giada Loi, Laura Benedetti, Franca Scocozza, Flavio Lorenzo Ronzoni, Maurilio Sampaolesi, Gabriella Cusella, Michele Conti, Gabriele Ceccarelli, Comparative analysis of different hydrogels for the bioprinting of 3D in vitro skeletal muscle models , Biomedical Science and Engineering: Vol. 2 No. 1 (2021)
- Sara Mantero, Federica Boschetti, Bioreactors as physiologicallike in vitro models , Biomedical Science and Engineering: Vol. 1 No. 1 (2020)
- Daniele Bianchi, Daniele Bissacco, Maurizio Domanin, Santi Trimarchi, Rodrigo Romarowski, Stefania Marconi, Ferdinando Auricchio, Michele Conti, Coupling in silico and ex vivo porcine model for the evaluation of biomechanical impact of TEVAR , Biomedical Science and Engineering: Vol. 2 No. 1 (2021)
You may also start an advanced similarity search for this article.
