ArticlePloS one2012
A phthalimide derivative that inhibits centrosomal clustering is effective on multiple myeloma.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients.Nature communications · 2015Pooled it
- CDK1‑induced regulation of p53 phosphorylation at Ser315 mediates cell cycle arrest and apoptosis of macrophages infected with clinical isolates ofMolecular medicine reports · 2026Article
- LIMK2 promotes centrosome clustering and cancer progression by activating MST4-mediated phosphorylation of NPM1.Oncogene · 2025Article
- Synthesis and Bioactivity of Phthalimide Analogs as Potential Drugs to Treat Schistosomiasis, a Neglected Disease of Poverty.Pharmaceuticals (Basel, Switzerland) · 2020Article
- The impact of mitotic errors on cell proliferation and tumorigenesis.Genes & development · 2018Review
- Synergistic blending of high-valued heterocycles inhibits growth of Plasmodium falciparum in culture and P. berghei infection in mouse model.Scientific reports · 2017Article
- Centrosome amplification, chromosomal instability and cancer: mechanistic, clinical and therapeutic issues.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2016Review
- A novel phthalimide derivative, TC11, has preclinical effects on high-risk myeloma cells and osteoclasts.PloS one · 2015Article
- MIP-2A is a novel target of an anilinoquinazoline derivative for inhibition of tumour cell proliferation.PloS one · 2013Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the introduction of newly developed drugs such as lenalidomide and bortezomib, patients with multiple myeloma are still difficult to treat and have a poor prognosis. In order to find novel drugs that are effective for multiple myeloma, we tested the antitumor activity of 29 phthalimide derivatives against several multiple myeloma cell lines. Among these derivatives, 2-(2,6-diisopropylphenyl)-5-amino-1H-isoindole-1,3- dione (TC11) was found to be a potent inhibitor of tumor cell proliferation and an inducer of apoptosis via activation of caspase-3, 8 and 9. This compound also showed in vivo activity against multiple myeloma cell line KMS34 tumor xenografts in ICR/SCID mice. By means of mRNA display selection on a microfluidic chip, the target protein of TC11 was identified as nucleophosmin 1 (NPM). Binding of TC11 and NPM monomer was confirmed by surface plasmon resonance. Immunofluorescence and NPM knockdown studies in HeLa cells suggested that TC11 inhibits centrosomal clustering by inhibiting the centrosomal-regulatory function of NPM, thereby inducing multipolar mitotic cells, which undergo apoptosis. NPM may become a novel target for development of antitumor drugs active against multiple myeloma.
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