ArticleBioorganic & medicinal chemistry2018
Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation.
Article in Bioorganic & medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 64 citations in OpenAlex.
- Closing the gap in aging science: unlocking the potential of nanoparticles in senescence therapy.Biogerontology · 2026Review
- Natural products targeting cytokine-regulated SASP inflammation networks in Ovarian cancer: Implications on immune escape and molecular resistance.Inflammopharmacology · 2026Review
- The Aging Microenvironment Shapes Angiogenic Remodeling in IBD-Associated Colorectal Carcinogenesis.Aging cell · 2026Review
- Thymoquinone and pentoxifylline modulate 5-fluorouracil-induced senescence and apoptosis in colorectal cancer spheroids.Research in pharmaceutical sciences · 2026Article
- Neurocognitive Aging Following Acute Illness: Pathobiology and a Framework for Developing Neurotherapeutic Agents.Brain and behavior · 2026Review
- Cellular senescence in Crohn's disease: a double-edged sword in intestinal fibrosis.Frontiers in immunology · 2026Review
- Accelerated biological aging: the role of chronic inflammation, weathering and novel therapeutic strategies.Frontiers in aging · 2026Review
- Effects of Chlorogenic Acid on Cellular Senescence in an In Vitro Model of 3T3-L1 Murine Adipocytes.Molecules (Basel, Switzerland) · 2026Article
- Piperlonguminine inhibits hen egg white lysozyme amyloid fibril formation and mitigates amyloid fibril-induced hepatocellular damage.Current research in food science · 2026Article
- Role of cellular senescence in hepatic diseases (Review).International journal of molecular medicine · 2025Review
- Synthesis, anticancer evaluation, preliminary mechanism study of novel 1, 2, 3-triazole-piperlongumine derivatives.Molecular diversity · 2025Article
- Unraveling the meta-hallmarks between senescent and tumor cells: A new perspective for senolytic drug discovery.Acta pharmaceutica Sinica. B · 2025Review
- Targeting DNA damage in ageing: towards supercharging DNA repair.Nature reviews. Drug discovery · 2025Review
- Hepatocytes as Model for Investigating Natural Senotherapeutic Compounds and Their Effects on Cell Cycle Dynamics and Genome Stability.International journal of molecular sciences · 2025Review
- Senotherapy for chronic lung disease.Pharmacological reviews · 2025Review
- Fisetin as a Blueprint for Senotherapeutic Agents - Elucidating Geroprotective and Senolytic Properties with Molecular Modeling.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Hydrogen Peroxide-Releasing Hydrogel-Mediated Cellular Senescence Model for Aging Research.Biomaterials research · 2025Article
- Decoding senescence of aging single cells at the nexus of biomaterials, microfluidics, and spatial omics.npj aging · 2024Review
- The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies.Biomedicines · 2024Review
- Cellular Aging and Senescence in Cancer: A Holistic Review of Cellular Fate Determinants.Aging and disease · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Selective clearance of senescent cells (SCs) has emerged as a potential therapeutic approach for age-related diseases, as well as chemotherapy- and radiotherapy-induced adverse effects. Through a cell-based phenotypic screening approach, we recently identified piperlongumine (PL), a dietary natural product, as a novel senolytic agent, referring to small molecules that can selectively kill SCs over normal or non-senescent cells. In an effort to establish the structure-senolytic activity relationships of PL analogues, we performed a series of structural modifications on the trimethoxyphenyl and the α,β-unsaturated δ-valerolactam rings of PL. We show that modifications on the trimethoxyphenyl ring are well tolerated, while the Michael acceptor on the lactam ring is critical for the senolytic activity. Replacing the endocyclic C2-C3 olefin with an exocyclic methylene at C2 render PL analogues 47-49 with increased senolytic activity. These α-methylene containing analogues are also more potent than PL in inducing ROS production in WI-38 SCs. Similar to PL, 47-49 reduce the protein levels of oxidation resistance 1 (OXR1), an important oxidative stress response protein that regulates the expression of a variety of antioxidant enzymes, in cells. This study represents a useful starting point toward the discovery of senolytic agents for therapeutic uses.
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.