{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liashkovich I"],"funding":["Deutsche Forschungsgemeinschaft","Coordenação de Aperfeiçoamento de Pessoal de Nível Superior","Ministry of Education and Science of the Russian Federation"],"pagination":["e10425"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10354767"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(4)"],"pubmed_abstract":["Clathrin-mediated endocytosis (CME) is an essential cell physiological process of broad biomedical relevance. Since the recent introduction of Pitstop-2 as a potent CME inhibitor, we and others have reported on substantial clathrin-independent inhibitory effects. Herein, we developed and experimentally validated a novel fluorescent derivative of Pitstop-2, termed RVD-127, to clarify Pitstop-2 diverse effects. Using RVD-127, we were able to trace additional protein targets of Pitstop-2. Besides inhibiting CME, Pitstop-2 and RVD-127 proved to directly and reversibly bind to at least two members of the small GTPase superfamily Ran and Rac1 with particularly high efficacy. Binding locks the GTPases in a guanosine diphosphate (GDP)-like conformation disabling their interaction with their downst"],"journal":["Bioengineering & translational medicine"],"pubmed_title":["Pitstop-2 and its novel derivative RVD-127 disrupt global cell dynamics and nuclear pores integrity by direct interaction with small GTPases."],"pmcid":["PMC10354767"],"funding_grant_id":["Finance Code 001","SH 167/6‐1","075‐15‐2022‐264","LI 2157/3‐1","SH 167/6‐2","SH 167/9‐1"],"pubmed_authors":["Gorelkin PV","Kolmogorov V","Stefanello ST","Bulk E","Kouzel IU","Haufe G","Liashkovich I","Mizdal CR","Dulebo A","Erofeev A","Shahin V","Vidyadharan R"],"additional_accession":[]},"is_claimable":false,"name":"Pitstop-2 and its novel derivative RVD-127 disrupt global cell dynamics and nuclear pores integrity by direct interaction with small GTPases.","description":"Clathrin-mediated endocytosis (CME) is an essential cell physiological process of broad biomedical relevance. Since the recent introduction of Pitstop-2 as a potent CME inhibitor, we and others have reported on substantial clathrin-independent inhibitory effects. Herein, we developed and experimentally validated a novel fluorescent derivative of Pitstop-2, termed RVD-127, to clarify Pitstop-2 diverse effects. Using RVD-127, we were able to trace additional protein targets of Pitstop-2. Besides inhibiting CME, Pitstop-2 and RVD-127 proved to directly and reversibly bind to at least two members of the small GTPase superfamily Ran and Rac1 with particularly high efficacy. Binding locks the GTPases in a guanosine diphosphate (GDP)-like conformation disabling their interaction with their downst","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jul","modification":"2026-06-02T12:03:34.307Z","creation":"2026-04-18T03:11:19.173Z"},"accession":"S-EPMC10354767","cross_references":{"pubmed":["37476059"],"doi":["10.1002/btm2.10425"]}}