ArticleAmerican journal of translational research2015
FL118, a novel camptothecin analogue, overcomes irinotecan and topotecan resistance in human tumor xenograft models.
Article in American journal of translational research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 40 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
- Novel Camptothecin Derivative 9c with Enhanced Antitumor Activity via NSA2-EGFR-P53 Signaling Pathway.International journal of molecular sciences · 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
- Targeting the inhibitors of apoptosis proteins (IAPs) to combat drug resistance in cancers.Frontiers in pharmacology · 2025Review
- Article
- Exploring the Synergistic Effect of Sildenafil and Green Tea Polyphenols on Breast Cancer Stem Cell-like Cells and their Parental Cells: A Potential Novel Therapeutic Approach.Anti-cancer agents in medicinal chemistry · 2024Article
- Small Molecule Inhibitors Targeting the "Undruggable" Survivin: The Past, Present, and Future from a Medicinal Chemist's Perspective.Journal of medicinal chemistry · 2023Review
- 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
- Role of the DEAD-box RNA helicase DDX5 (p68) in cancer DNA repair, immune suppression, cancer metabolic control, virus infection promotion, and human microbiome (microbiota) negative influence.Journal of experimental & clinical cancer research : CR · 2023Review
- Survivin Small Molecules Inhibitors: Recent Advances and Challenges.Molecules (Basel, Switzerland) · 2023Review
- Synthesis and Biological Evaluation of 20(S)-Substituted FL118 Conjugates as Novel Antitumor Agents.Journal of molecular structure · 2022Article
- Preparation of a camptothecin analog FLQY2 self-micelle solid dispersion with improved solubility and bioavailability.Journal of nanobiotechnology · 2022Article
- Identification of a novel immune-inflammatory signature of COVID-19 infections, and evaluation of pharmacokinetics and therapeutic potential of RXn-02, a novel small-molecule derivative of quinolone.Computers in biology and medicine · 2022Article
- Investigation of the Uptake and Transport of Two Novel Camptothecin Derivatives in Caco-2 Cell Monolayers.Molecules (Basel, Switzerland) · 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
- 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
- Review
- Dual Inhibition of P-gp and BCRP Improves Oral Topotecan Bioavailability in Rodents.Pharmaceutics · 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Irinotecan and topotecan are the only camptothecin analogues approved by the FDA for cancer treatment. However, inherent and/or acquired irinotecan and topotecan resistance is a challenging issue in clinical practice. In this report, we showed that FL118, a novel camptothecin analogue, effectively obliterated human xenograft tumors that acquire irinotecan and topotecan resistance. Consistent with this finding, Pharmacokinetics studies indicated that FL118 rapidly clears from circulation, while effectively accumulating in tumors with a long elimination half-life. Consistent with our previous studies on irinotecan, FL118 exhibited ≥25 fold more effectiveness than topotecan at inhibiting cancer cell growth and colony formation; we further showed that although topotecan can inhibit the expression of survivin, Mcl-1, XIAP or cIAP2, its effectiveness is about 10-100 fold weaker than FL118. Lastly, in contrast to both SN-38 (active metabolite of irinotecan) and topotecan are substrates of the efflux pump proteins P-gp/MDR1 and ABCG2/BCRP, FL118 is not a substrate of P-gp and ABCG2. Consistently, sildenafil, a multiple efflux pump inhibitor, sensitized SN-38 much more than these of the ABCG2-selective inhibitor KO143 in growth inhibition of SW620 and HCT-8 cells. In contrast, both inhibitors showed no effect on FL118 efficacy. Given that both P-gp and ABCG2 express in SW620 and HCT-8 cells and FL118 is not a substrate for P-gp and ABCG2, this suggests that FL118 appears to bypass multiple efflux pump protein-induced resistance, which may contribute to FL118 overcoming irinotecan and topotecan resistance in vivo. These new findings provide renewed perspectives for further development of FL118 for clinical applications.
Indexed as
Identifiers
26692923PMC4656756W2215145163What 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.