ArticleThe Journal of clinical investigation2019
Ligand-based design identifies a potent NUPR1 inhibitor exerting anticancer activity via necroptosis.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 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
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Necroptosis in pancreatic cancer: Molecular mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Pooled it
- Beyond the structure-function paradigm: A comprehensive review of intrinsically disordered proteins.Biochemistry and biophysics reports · 2026Review
- Deciphering the rules of regulated cell death subroutines by in silico methods.Journal of advanced research · 2026Review
- Nuclear protein 1 is a cell death regulator in primary human airway epithelial cells and reduced in idiopathic pulmonary fibrosis.Scientific reports · 2026Article
- NUPR1 as a central stress-adaptation node in cancer: integrating metabolic rewiring, cell death, and therapy resistance.Journal of biomedical science · 2026Review
- Liquid liquid phase separation of the intrinsically disordered protein JPT2 compartmentalizes components of NAADP-evoked CabioRxiv : the preprint server for biology · 2026Article
- Histone H4K8 lactylation promotes glioblastoma progression by inducing NUPR1-mediated autophagosome‒lysosome fusion.Theranostics · 2026Article
- NUPR1 in breast cancer: mechanisms and potential applications.Frontiers in physiology · 2026Review
- Necroptotic signaling orchestrates glioblastoma malignancy and potentiates temozolomide response.Cell death & disease · 2025Article
- Synergistic antitumor activity of sorafenib and the NUPR1 inhibitor LZX-2-73 in multiple cancer models.Cell death & disease · 2025Article
- Targeting protein disorder: the next hurdle in drug discovery.Nature reviews. Drug discovery · 2025Review
- The intrinsically disordered protein NUPR1 binds to phospholipids.Protein science : a publication of the Protein Society · 2025Article
- Mechanisms of induced resistance to the antitumoral agent ZZW-115 in pancreas ductal adenocarcinoma.Scientific reports · 2025Article
- Self-assembling dendrimer nanodrug formulations for decreased hERG-related toxicity and enhanced therapeutic efficacy.Science advances · 2025Article
- FTO facilitates colorectal cancer chemoresistance via regulation of NUPR1-dependent iron homeostasis.Redox biology · 2025Article
- NUPR1 Promotes Radioresistance in Colorectal Cancer Cells by Inhibiting Ferroptosis.Journal of cellular and molecular medicine · 2025Article
- The versatility of phenothiazines as an anticancer drug scaffold.Future medicinal chemistry · 2025Article
- Development of an efficient NUPR1 inhibitor with anticancer activity.Scientific reports · 2024Article
- Suppression of NUPR1 in fibroblast-like synoviocytes reduces synovial fibrosis via the Smad3 pathway.Journal of translational medicine · 2024Article
- Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer.Acta pharmaceutica Sinica. B · 2024Review
3 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
12 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intrinsically disordered proteins (IDPs) are emerging as attractive drug targets by virtue of their prevalence in various diseases including cancer. Drug development targeting IDPs is challenging because they have dynamical structure features and conventional drug design is not applicable. NUPR1 is an IDP playing an important role in pancreatic cancer. We previously reported that Trifluoperazine (TFP), an antipsychotic agent, was capable of binding to NUPR1 and inhibiting tumors growth. Unfortunately, TFP showed strong central nervous system side-effects. In this work, we undertook a multidisciplinary approach to optimize TFP, based on the synergy of computer modeling, chemical synthesis, and a variety of biophysical, biochemical and biological evaluations. A family of TFP-derived compounds was produced and the most active one, named ZZW-115, showed a dose-dependent tumor regression with no neurological effects and induced cell death mainly by necroptosis. This study opens a new perspective for drug development against IDPs, demonstrating the possibility of successful ligand-based drug design for such challenging targets.
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.