{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lucena-Agell D"],"funding":["Ministerio de Ciencia e Innovación","Fundación Tatiana Pérez de Guzmán el Bueno","European Commission","PharmaMar"],"pagination":["2619-2630"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10895673"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["67(4)"],"pubmed_abstract":["Targeting microtubules is the most effective wide-spectrum pharmacological strategy in antitumoral chemotherapy, and current research focuses on reducing main drawbacks: neurotoxicity and resistance. PM534 is a novel synthetic compound derived from the Structure-Activity-Relationship study on the natural molecule PM742, isolated from the sponge of the <i>order Lithistida</i>, family <i>Theonellidae</i>, genus <i>Discodermia</i> (du Bocage 1869). PM534 targets the entire colchicine binding domain of tubulin, covering four of the five centers of the pharmacophore model. Its nanomolar affinity and high retention time modulate a strikingly high antitumor activity that efficiently overrides two resistance mechanisms in cells (detoxification pumps and tubulin βIII isotype overexpression). Furthe"],"journal":["Journal of medicinal chemistry"],"pubmed_title":["PM534, an Optimized Target-Protein Interaction Strategy through the Colchicine Site of Tubulin."],"pmcid":["PMC10895673"],"funding_grant_id":["PID2022-136765OB-I00","PID2021-123399OB-I00","PID2020-117580RB-I00"],"pubmed_authors":["Martinez-Diez M","Hortiguela R","Plaza-Menacho I","Gimenez-Abian JF","Lucena-Agell D","Oliva MA","Aviles P","Santamaria-Nunez G","Cuevas C","Guillen MJ","Matesanz R","Diaz JF","Alvarez-Bernad B","Contreras J"],"additional_accession":[]},"is_claimable":false,"name":"PM534, an Optimized Target-Protein Interaction Strategy through the Colchicine Site of Tubulin.","description":"Targeting microtubules is the most effective wide-spectrum pharmacological strategy in antitumoral chemotherapy, and current research focuses on reducing main drawbacks: neurotoxicity and resistance. PM534 is a novel synthetic compound derived from the Structure-Activity-Relationship study on the natural molecule PM742, isolated from the sponge of the <i>order Lithistida</i>, family <i>Theonellidae</i>, genus <i>Discodermia</i> (du Bocage 1869). PM534 targets the entire colchicine binding domain of tubulin, covering four of the five centers of the pharmacophore model. Its nanomolar affinity and high retention time modulate a strikingly high antitumor activity that efficiently overrides two resistance mechanisms in cells (detoxification pumps and tubulin βIII isotype overexpression). Furthe","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-05-29T12:34:03.861Z","creation":"2025-02-19T01:42:02.224Z"},"accession":"S-EPMC10895673","cross_references":{"pubmed":["38294341"],"doi":["10.1021/acs.jmedchem.3c01775"]}}