{"doi":"10.1016/j.molcel.2020.06.008","title":"Pharmaceutical-Grade Rigosertib Is a Microtubule-Destabilizing Agent","abstract":"We recently used CRISPRi/a-based chemical-genetic screens and cell biological, biochemical, and structural assays to determine that rigosertib, an anti-cancer agent in phase III clinical trials, kills cancer cells by destabilizing microtubules. Reddy and co-workers (Baker et al., 2020, this issue of Molecular Cell) suggest that a contaminating degradation product in commercial formulations of rigosertib is responsible for the microtubule-destabilizing activity. Here, we demonstrate that cells treated with pharmaceutical-grade rigosertib (>99.9% purity) or commercially obtained rigosertib have qualitatively indistinguishable phenotypes across multiple assays. The two formulations have indistinguishable chemical-genetic interactions with genes that modulate microtubule stability, both destabilize microtubules in cells and in vitro, and expression of a rationally designed tubulin mutant with a mutation in the rigosertib binding site (L240F TUBB) allows cells to proliferate in the presence of either formulation. Importantly, the specificity of the L240F TUBB mutant for microtubule-destabilizing agents has been confirmed independently. Thus, rigosertib kills cancer cells by destabilizing microtubules, in agreement with our original findings.","journal":"Molecular Cell","year":2020,"id":60590,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":61,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":320109,"name":"Yuwen Chen","orcid":"0000-0003-3025-7096","position":1,"is_corresponding":false},{"id":319827,"name":"Luke A. Gilbert","orcid":"0000-0001-5854-0825","position":2,"is_corresponding":false},{"id":255919,"name":"Max A. Horlbeck","orcid":"0000-0002-3875-871X","position":3,"is_corresponding":false},{"id":320110,"name":"Lenno Krenning","orcid":"0000-0001-6696-0512","position":4,"is_corresponding":false},{"id":321829,"name":"Grégory Menchon","orcid":null,"position":5,"is_corresponding":false},{"id":320111,"name":"Ankit Rai","orcid":"0000-0002-3732-3597","position":6,"is_corresponding":false},{"id":321830,"name":"Min Y. Cho","orcid":null,"position":7,"is_corresponding":false},{"id":321831,"name":"Jacob J. Stern","orcid":null,"position":8,"is_corresponding":false},{"id":320112,"name":"A.E. Prota","orcid":"0000-0003-0875-5339","position":9,"is_corresponding":false},{"id":218683,"name":"Martin Kampmann","orcid":"0000-0002-3819-7019","position":10,"is_corresponding":false},{"id":85033,"name":"Anna Akhmanova","orcid":"0000-0002-9048-8614","position":11,"is_corresponding":false},{"id":320113,"name":"Michel O. Steinmetz","orcid":"0000-0001-6157-3687","position":12,"is_corresponding":false},{"id":289555,"name":"Marvin E. Tanenbaum","orcid":"0000-0001-8762-0090","position":13,"is_corresponding":false},{"id":17890,"name":"Jonathan S. Weissman","orcid":"0000-0003-2445-670X","position":14,"is_corresponding":false},{"id":251069,"name":"Marco Jost","orcid":"0000-0002-1369-4908","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T21:09:05.493770Z","pmid":"32619469","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}