ArticleJournal of biomedical science2022
Preclinical validation and phase I trial of 4-hydroxysalicylanilide, targeting ribonucleotide reductase mediated dNTP synthesis in multiple myeloma.
Article in Journal of biomedical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03670173 (Safety and Efficacy Assessments of Osalmid in the Treatment of Multiple Myeloma), which is not on this map. Cited by 13 papers.
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.
Safety and Efficacy Assessments of Osalmid in the Treatment of Multiple Myeloma
Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Osalmid inhibits lung adenocarcinoma progression and enhances EGFR-TKI responses: a preclinical and translational study.Translational lung cancer research · 2026Article
- Article
- Targeting endosomal trafficking-mediated antigen escape to resensitize myeloma to CAR-T therapy.Journal for immunotherapy of cancer · 2026Article
- E2 ubiquitin-conjugating enzyme Ubc11 regulates Rst2 protein stability in the fission yeast Schizosaccharomyces pombe.Archives of microbiology · 2025Article
- Discovery of novel antimyeloma agents targeting TRIP13 by molecular modeling and bioassay.RSC medicinal chemistry · 2025Article
- Targeting enolase 1 reverses bortezomib resistance in multiple myeloma through YWHAZ/Parkin axis.Journal of biomedical science · 2025Article
- Non-Cicatricial Alopecia and Its Association with Anthropometric Measurements and Nutritional Laboratory Markers.Life (Basel, Switzerland) · 2024Article
- Synergistic Effect of a Combination of Proteasome and Ribonucleotide Reductase Inhibitors in a Biochemical Model of the YeastInternational journal of molecular sciences · 2024Article
- Ribosomal protein S3 mediates drug resistance of proteasome inhibitor: potential therapeutic application in multiple myeloma.Haematologica · 2024Article
- The novel norcantharidin derivative DCZ5417 suppresses multiple myeloma progression by targeting the TRIP13-MAPK-YWHAE signaling pathway.Journal of translational medicine · 2023Article
- Structure of a ribonucleotide reductase R2 protein radical.Science (New York, N.Y.) · 2023Article
- Yeast Ribonucleotide Reductase Is a Direct Target of the Proteasome and Provides Hyper Resistance to the Carcinogen 4-NQO.Journal of fungi (Basel, Switzerland) · 2023Article
- Characteristics of the immune microenvironment associated with RRM2 expression and its application to PD-L1/PD-1 inhibitors in lung adenocarcinoma.American journal of cancer research · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundAberrant DNA repair pathways contribute to malignant transformation or disease progression and the acquisition of drug resistance in multiple myeloma (MM); therefore, these pathways could be therapeutically exploited. Ribonucleotide reductase (RNR) is the rate-limiting enzyme for the biosynthesis of deoxyribonucleotides (dNTPs), which are essential for DNA replication and DNA damage repair. In this study, we explored the efficacy of the novel RNR inhibitor, 4-hydroxysalicylanilide (HDS), in myeloma cells and xenograft model. In addition, we assessed the clinical activity and safety of HDS in patients with MM.
methodsWe applied bioinformatic, genetic, and pharmacological approaches to demonstrate that HDS was an RNR inhibitor that directly bound to RNR subunit M2 (RRM2). The activity of HDS alone or in synergy with standard treatments was evaluated in vitro and in vivo. We also initiated a phase I clinical trial of single-agent HDS in MM patients (ClinicalTrials.gov: NCT03670173) to assess safety and efficacy.
resultsHDS inhibited the activity of RNR by directly targeting RRM2. HDS decreased the RNR-mediated dNTP synthesis and concomitantly inhibited DNA damage repair, resulting in the accumulation of endogenous unrepaired DNA double-strand breaks (DSBs), thus inhibiting MM cell proliferation and inducing apoptosis. Moreover, HDS overcame the protective effects of IL-6, IGF-1 and bone marrow stromal cells (BMSCs) on MM cells. HDS prolonged survival in a MM xenograft model and induced synergistic anti-myeloma activity in combination with melphalan and bortezomib. HDS also showed a favorable safety profile and demonstrated clinical activity against MM.
conclusionsOur study provides a rationale for the clinical evaluation of HDS as an anti-myeloma agent, either alone or in combination with standard treatments for MM.
trial registrationClinicalTrials.gov, NCT03670173, Registered 12 September 2018.
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.