ArticleCell death & disease2015
Antitumour potential of BPT: a dual inhibitor of cdk4 and tubulin polymerization.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- A Systematic Review of Recently Reported Marine Derived Natural Product Kinase Inhibitors.Marine drugs · 2019Pooled it
- Advancements in CDK-based Dual-target Inhibitors for Cancer Therapy.Current medicinal chemistry · 2026Review
- A machine learning-based analysis method for small molecule high content screening of three-dimensional cancer spheroid morphology.Molecular pharmacology · 2025Article
- A New Mild Method for Synthesis of Marine Alkaloid Fascaplysin and Its Therapeutically Promising Derivatives.Marine drugs · 2023Article
- Marine-Derived Lead Fascaplysin: Pharmacological Activity, Total Synthesis, and Structural Modification.Marine drugs · 2023Review
- Therapeutic significance of molecular hybrids for breast cancer research and treatment.RSC medicinal chemistry · 2023Review
- Synergistic cytotoxicity of the CDK4 inhibitor Fascaplysin in combination with EGFR inhibitor Afatinib against Non-small Cell Lung Cancer.Investigational new drugs · 2022Article
- Advances in thiosemicarbazone metal complexes as anti-lung cancer agents.Frontiers in pharmacology · 2022Review
- Bioactive Compounds with Antiglioma Activity from Marine Species.Biomedicines · 2021Review
- Article
- Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy.Medicinal research reviews · 2019Review
- Diastereoselective approach to rationally design tetrahydro-β-carboline-isatin conjugates as potential SERMs against breast cancer.RSC advances · 2019Article
- Anticancer Activity of Fascaplysin against Lung Cancer Cell and Small Cell Lung Cancer Circulating Tumor Cell Lines.Marine drugs · 2018Article
- Article
- Identification of karanjin isolated from the Indian beech tree as a potent CYP1 enzyme inhibitor with cellular efficacyMedChemComm · 2018Article
- Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK.Molecules (Basel, Switzerland) · 2017Article
- Microtubule Depolymerization by Kinase Inhibitors: Unexpected Findings of Dual Inhibitors.International journal of molecular sciences · 2017Review
- Non-kinase targets of protein kinase inhibitors.Nature reviews. Drug discovery · 2017Review
- Decreased CDK10 expression correlates with lymph node metastasis and predicts poor outcome in breast cancer patients - a short report.Cellular oncology (Dordrecht, Netherlands) · 2015Article
- Cytotoxic activity of the MK2 inhibitor CMPD1 in glioblastoma cells is independent of MK2.Cell death discovery · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The marine natural product fascaplysin (1) is a potent Cdk4 (cyclin-dependent kinase 4)-specific inhibitor, but is toxic to all cell types possibly because of its DNA-intercalating properties. Through the design and synthesis of numerous fascaplysin analogues, we intended to identify inhibitors of cancer cell growth with good therapeutic window with respect to normal cells. Among various non-planar tryptoline analogues prepared, N-(biphenyl-2-yl) tryptoline (BPT, 6) was identified as a potent inhibitor of cancer cell growth and free from DNA-binding properties owing to its non-planar structure. This compound was tested in over 60 protein kinase assays. It displayed inhibition of Cdk4-cyclin D1 enzyme in vitro far more potently than many other kinases including Cdk family members. Although it blocks growth of cancer cells deficient in the mitotic-spindle checkpoint at the G0/G1 phase of the cell cycle, the block occurs primarily at the G2/M phase. BPT inhibits tubulin polymerization in vitro and acts as an enhancer of tubulin depolymerization of paclitaxel-stabilized tubulin in live cells. Western blot analyses indicated that, in p53-positive cells, BPT upregulates the expression of p53, p21 and p27 proteins, whereas it downregulates the expression of cyclin B1 and Cdk1. BPT selectively kills SV40-transformed mouse embryonic hepatic cells and human fibroblasts rather than untransformed cells. BPT inhibited the growth of several human cancer cells with an IC50<1 μM. The pharmacokinetic study in BALB/c mice indicated good plasma exposure after intravenous administration. It was found to be efficacious at 1/10th the maximum-tolerated dose (1000 mg/kg) against human tumours derived from HCT-116 (colon) and NCI-H460 (lung) cells in SCID (severe-combined immunodeficient) mice models. BPT is a relatively better anticancer agent than fascaplysin with an unusual ability to block two overlapping yet crucial phases of the cell cycle, mitosis and G0/G1. Its ability to effectively halt tumour growth in human tumour-bearing mice would suggest that BPT has the potential to be a candidate for further clinical development.
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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.