ArticleProceedings of the National Academy of Sciences of the United States of America2002
Suppression of bone resorption by madindoline A, a novel nonpeptide antagonist to gp130.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 89 citations in OpenAlex.
- Interleukin-6 serves as a critical factor in various cancer progression and therapy.Medical oncology (Northwood, London, England) · 2024Review
- Carbohydrate-Small Molecule Hybrids as Lead Compounds Targeting IL-6 Signaling.Molecules (Basel, Switzerland) · 2023Article
- The Role of IL-6 in Cancer Cell Invasiveness and Metastasis-Overview and Therapeutic Opportunities.Cells · 2022Review
- New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity.Pharmaceutics · 2022Article
- IL-6 in the Ecosystem of Head and Neck Cancer: Possible Therapeutic Perspectives.International journal of molecular sciences · 2021Review
- Interleukin-6: Molecule in the Intersection of Cancer, Ageing and COVID-19.International journal of molecular sciences · 2020Review
- Structural Understanding of Interleukin 6 Family Cytokine Signaling and Targeted Therapies: Focus on Interleukin 11.Frontiers in immunology · 2020Review
- Novel small molecule IL-6 inhibitor suppresses autoreactive Th17 development and promotes TClinical and experimental immunology · 2019Article
- Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer.Nature reviews. Immunology · 2018Review
- Bazedoxifene enhances the anti-tumor effects of cisplatin and radiation treatment by blocking IL-6 signaling in head and neck cancer.Oncotarget · 2017Article
- Growth-suppressive activity of raloxifene on liver cancer cells by targeting IL-6/GP130 signaling.Oncotarget · 2017Article
- Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer.Oncotarget · 2016Review
- The balance between soluble receptors regulating IL-6 trans-signaling is predictive for the RANKL/osteoprotegerin ratio in postmenopausal women with rheumatoid arthritis.Rheumatology international · 2012Article
- Synthesis of (+)-madindoline A and (+)-madindoline B.Organic letters · 2007Article
- Glycoprotein 130 regulates bone turnover and bone size by distinct downstream signaling pathways.The Journal of clinical investigation · 2004Article
- Role of cytokines in postmenopausal bone loss.Current osteoporosis reports · 2003Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL-6 is a multifunctional cytokine involved in regulation of differentiation, antibody production, and growth of certain types of tumor cells. Its excessive production plays a major role in pathogenesis of multiple myeloma and postmenopausal osteoporosis. In the course of a screening program aimed at IL-6 inhibitor from microbial products, we found madindoline A (MDL-A) and madindoline B, which have a fuloindoline structure with diketocyclopentene bound to the methyl group. MDL-A has no cytotoxic activities. It inhibited only activities of both IL-6 and IL-11 without affecting the IL-6-specific signal transduction cascade, JAK2/STAT3. In a dose-dependent manner [(3)H]MDL-A binds to gp130, which is a signal transducing 130-kDa glycoprotein, but formation of the trimeric complex IL-6/IL-6 receptor/gp130 was not inhibited, suggesting that MDL-A suppresses dimerization of trimeric complexes. Not only did MDL-A markedly inhibit IL-6- and IL-11-induced osteoclastogenesis in vitro, but it also inhibited IL-6-stimulated serum amyloid A production and bone resorption in an experimental model of postmenopausal osteoporosis in vivo by a different mechanism from that of 17beta-estradiol. Here we show that MDL-A has a highly selective inhibitory effect on IL-6 and IL-11 activities by inhibiting a gp130 activity while suppressing bone loss in ovariectomized mice. MDL-A is anticipated as a lead compound for treatment of hormone-dependent postmenopausal osteoporosis, which has no serious side effects, and as a new mechanism of action, gp130 blocking.
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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.