ArticleAmerican journal of cancer research2017
Topoisomerase I (Top1): a major target of FL118 for its antitumor efficacy or mainly involved in its side effects of hematopoietic toxicity?
Article in American journal of cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 29 citations in OpenAlex.
- DDX5 (p68) and UbE2T as emerging superior cancer therapeutic targets: dual molecular glue target degradation by FL118 for conquering difficult-to-treat cancers.Journal of experimental & clinical cancer research : CR · 2026Review
- FL496, an FL118-derived small molecule, induces growth inhibition, senescence, and apoptosis of malignant pleural mesothelioma (MPM) cells, and exhibits anti-MPM tumor efficacy strikingly superior to the pemetrexed-cisplatin combination.Journal of experimental & clinical cancer research : CR · 2025Article
- Design, synthesis and investigation of biological activity and mechanism of fluoroaryl-substituted derivatives at the FL118 position 7.European journal of medicinal chemistry · 2025Article
- Study on the design, synthesis, and activity of anti-tumor staple peptides targeting MDM2/MDMX.Frontiers in chemistry · 2024Article
- Structure-Activity Relationship of FL118 Platform Position 7 Versus Position 9-Derived Compounds and Their Mechanism of Action and Antitumor Activity.Journal of medicinal chemistry · 2023Article
- Small Molecule Inhibitors Targeting the "Undruggable" Survivin: The Past, Present, and Future from a Medicinal Chemist's Perspective.Journal of medicinal chemistry · 2023Review
- SUMO Proteomics Analyses Identify Protein Inhibitor of Activated STAT-Mediated Regulatory Networks Involved in Cell Cycle and Cell Proliferation.Journal of proteome research · 2023Article
- Survivin Small Molecules Inhibitors: Recent Advances and Challenges.Molecules (Basel, Switzerland) · 2023Review
- Preparation of a camptothecin analog FLQY2 self-micelle solid dispersion with improved solubility and bioavailability.Journal of nanobiotechnology · 2022Article
- FL118, acting as a 'molecular glue degrader', binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c-Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy.Clinical and translational medicine · 2022Article
- Grouped-seq for integrated phenotypic and transcriptomic screening of patient-derived tumor organoids.Nucleic acids research · 2022Article
- Kidney cancer biomarkers and targets for therapeutics: survivin (BIRC5), XIAP, MCL-1, HIF1α, HIF2α, NRF2, MDM2, MDM4, p53, KRAS and AKT in renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2021Review
- Lipid-derived electrophiles mediate the effects of chemotherapeutic topoisomerase I poisons.Cell chemical biology · 2021Article
- Kras mutation subtypes distinctly affect colorectal cancer cell sensitivity to FL118, a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX.American journal of translational research · 2021Article
- Multiple functions of the DEAD-box RNA helicase, DDX5 (p68), make DDX5 a superior oncogenic biomarker and target for targeted cancer therapy.American journal of cancer research · 2021Review
- Article
- Synthesis and biological activities of two camptothecin derivatives against Spodoptera exigua.Scientific reports · 2019Article
- Cancer therapeutics using survivin BIRC5 as a target: what can we do after over two decades of study?Journal of experimental & clinical cancer research : CR · 2019Review
- Uptake and efflux of FL118 and two FL118 derivatives in 3D cell model.Cytotechnology · 2019Article
- An ABCG2 non-substrate anticancer agent FL118 targets drug-resistant cancer stem-like cells and overcomes treatment resistance of human pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
FL118 is a novel camptothecin (CPT) analogue that possesses exceptional antitumor efficacy in human tumor animal models. To date, two CPT analogues, irinotecan and topotecan, have been approved by the FDA for cancer treatment. FL118 exhibits superior antitumor activity over irinotecan and topotecan, and effectively overcomes the irinotecan- or topotecan-resistant human tumors in animal models. Accordingly, FL118 selectively inhibits the expression of multiple cancer-associated proteins (survivin, Mcl-1, XIAP, cIAP2, MdmX). However, FL118 has hematopoietic toxicity similar to irinotecan and topotecan, suggesting that FL118's hematopoietic toxicity may share a mechanism similar to irinotecan and topotecan. It is known that CPTs including irinotecan, SN-38 (active metabolite of irinotecan) and topotecan are topoisomerase I (Top1) inhibitors. However, the evidence from our studies failed to reveal that FL118 is a better Top1 inhibitor than SN-38. It was documented that Top1 expression level is positively associated with CPTs' sensitivity. Low Top1 expression links to CPTs' resistance. In contrast to these findings, we found that human colorectal tumor sensitivity to FL118 is irrelevant to the expression level of Top1 protein. FL118 can show high antitumor efficacy in Top1-negative tumors, while Top1 highly positive tumors can exhibit FL118 resistance. This suggests that the presence of Top1 target is not critical for FL118 antitumor activity. In other words, targeting Top1 by FL118 may not play a major role for its antitumor efficacy. However, studies indicate that FL118 can bind to, and inhibit Top1 activity. This raises the possibility that inhibition of Top1 by FL118 may predominantly be involved in hematopoietic toxicity, but not in FL118 antitumor activity. In this article, we will summarize existing observations and provide our up-to-date research results to support our opinion on this important topic.
Indexed as
Identifiers
28337384PMC5336509W2788243213What 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.