{"doi":"10.1101/2020.06.23.168005","title":"A novel and highly effective mitochondrial uncoupling drug in T-cell leukemia","abstract":"Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy. Despite recent advances in treatments with intensified chemotherapy regimens, relapse rates and associated morbidities remain high. In this context, metabolic dependencies have emerged as a druggable opportunity for the treatment of leukemia. Here, we tested the antileukemic effects of MB1-47, a newly developed mitochondrial uncoupling compound. MB1-47 treatment in T-ALL cells robustly inhibited cell proliferation via both cytostatic and cytotoxic effects as a result of compromised mitochondrial energy and macromolecule depletion, which severely impair nucleotide biosynthesis. Mechanistically, acute treatment with MB1-47 in primary leukemias promoted AMPK activation and downregulation of mTOR signaling, stalling anabolic pathways that support leukemic cell survival. Indeed, MB1-47 treatment in mice harboring murine NOTCH1-induced leukemias or human T-ALL PDXs led to a potent antileukemic effect with 2-fold extension in survival without overlapping toxicities. Overall, our findings demonstrate a critical role for mitochondrial oxidative phosphorylation in T-ALL and uncover MB1-47-driven mitochondrial uncoupling as a novel therapeutic strategy for the treatment of this disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122848,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"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":564742,"name":"Bin Cao","orcid":"0000-0002-2442-994X","position":1,"is_corresponding":false},{"id":267436,"name":"Olga Lancho","orcid":"0000-0001-5819-4715","position":2,"is_corresponding":false},{"id":564743,"name":"Eric Chiles","orcid":"0000-0003-3354-607X","position":3,"is_corresponding":false},{"id":564744,"name":"Amer Alasadi","orcid":"0000-0001-6082-1597","position":4,"is_corresponding":false},{"id":501338,"name":"Shirley Luo","orcid":"0000-0003-4828-8042","position":5,"is_corresponding":false},{"id":565449,"name":"David J. Augeri","orcid":null,"position":6,"is_corresponding":false},{"id":267439,"name":"Sonia Minuzzo","orcid":"0000-0003-2588-6058","position":7,"is_corresponding":false},{"id":267440,"name":"Stefano Indraccolo","orcid":"0000-0002-4810-7136","position":8,"is_corresponding":false},{"id":244441,"name":"Xiaoyang Su","orcid":"0000-0001-8081-1396","position":9,"is_corresponding":false},{"id":564745,"name":"Shengkan Jin","orcid":"0000-0002-5979-7232","position":10,"is_corresponding":false},{"id":267441,"name":"Daniel Herranz","orcid":"0000-0003-1768-5969","position":11,"is_corresponding":false},{"id":267438,"name":"Victoria da Silva-Diz","orcid":"0000-0002-1508-2999","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T23:14:55.385653Z","pmid":null,"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":[]}