ArticleNature medicine2018
A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 267 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
267 citing papers in PubMed, 1 synthesis or guideline pooled it, 441 citations in OpenAlex.
- Patients with Parkinson's disease predict a lower incidence of colorectal cancer.BMC geriatrics · 2021Pooled it
- Genome-wide CRISPR screens identify an RXR-MYLIP-LDLR axis regulating BH3 mimetic sensitivity in peripheral T-cell lymphomas.Oncogene · 2026Article
- The ubiquitin-activating enzyme inhibitor TAK-243 activates store-operated CaBiochimica et biophysica acta. Molecular cell research · 2026Article
- Targeted degradation of protein in hematologic malignancies: mechanisms, therapeutic strategies, and clinical prospects.Cancer gene therapy · 2026Review
- The role of E3 ubiquitin ligases in selective types of macroautophagy.EMBO reports · 2026Review
- A viral ORFeome library for systems-level genetic dissection of host-pathogen interactions.Cell · 2026Article
- Discovery and Characterization of Inhibitors of Ubiquitin-Like Modifier Activating Enzyme 5 (UBA5): Targeting the UFMylation Pathway in Cancer and Neurodegenerative Diseases.ACS chemical biology · 2026Article
- Decoding immunotherapy resistance in multiple myeloma: genetic insights and approaches to counter resistance.Science China. Life sciences · 2026Review
- Cellular assembly and functional resilience of the mammalian RNA exosome.The EMBO journal · 2026Article
- Expanding the repertoire of chemically induced covalent neoantigens.Nature chemical biology · 2026Article
- Systematic Targeting of Protein Complexes with Molecular COUPLrs.Cancer discovery · 2026Article
- Inhibition of USP7 Destabilizes the Noncanonical PRC1.1 Complex and Induces Neuroblastoma Differentiation.Molecular cancer research : MCR · 2026Article
- Article
- The vesicular stomatitis virus matrix protein promotes FACT subunit depletion to suppress the FEAR pathway.PLoS pathogens · 2026Article
- Incorporation of the Trifluoromethylthio Group (CFThe Journal of organic chemistry · 2026Review
- TRIM21 induces selective autophagy of viruses and bacteria.Molecular cell · 2026Article
- UBA1 drives cell cycle to promote malignancy and serves as a therapeutic target in Ewing Sarcoma.BMC cancer · 2026Article
- Regulation of HPV-16 infection by ubiquitination of the L1 major capsid protein.Journal of virology · 2026Article
- IRE1-XBP1driven induction of TMED9 stabilizes ATF6 during ER stress to promote cell survival.Cellular & molecular biology letters · 2026Article
- Highly specific intracellular ubiquitination of a small molecule.Nature chemical biology · 2026Article
207 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
39 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitin-proteasome system (UPS) comprises a network of enzymes that is responsible for maintaining cellular protein homeostasis. The therapeutic potential of this pathway has been validated by the clinical successes of a number of UPS modulators, including proteasome inhibitors and immunomodulatory imide drugs (IMiDs). Here we identified TAK-243 (formerly known as MLN7243) as a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE), the primary mammalian E1 enzyme that regulates the ubiquitin conjugation cascade. TAK-243 treatment caused depletion of cellular ubiquitin conjugates, resulting in disruption of signaling events, induction of proteotoxic stress, and impairment of cell cycle progression and DNA damage repair pathways. TAK-243 treatment caused death of cancer cells and, in primary human xenograft studies, demonstrated antitumor activity at tolerated doses. Due to its specificity and potency, TAK-243 allows for interrogation of ubiquitin biology and for assessment of UAE inhibition as a new approach for cancer treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.