ArticleMolecular cancer2009
Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors.
Article in Molecular cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- And-1 Coordinates with the FANCM Complex to Regulate Fanconi Anemia Signaling and Cisplatin Resistance.Cancer research · 2022Article
- Fanconi Anemia Pathway in Colorectal Cancer: A Novel Opportunity for Diagnosis, Prognosis and Therapy.Journal of personalized medicine · 2022Review
- Dienone Compounds: Targets and Pharmacological Responses.Journal of medicinal chemistry · 2020Article
- Methodology for the identification of small molecule inhibitors of the Fanconi Anaemia ubiquitin E3 ligase complex.Scientific reports · 2020Article
- Inhibitors of the Fanconi anaemia pathway as potential antitumour agents for ovarian cancer.Exploration of targeted anti-tumor therapy · 2020Review
- Fanconi anemia pathway as a prospective target for cancer intervention.Cell & bioscience · 2020Review
- Xenbase: Facilitating the Use ofFrontiers in physiology · 2019Review
- Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines.Chemistry Central journal · 2018Article
- Fanconi anaemia and cancer: an intricate relationship.Nature reviews. Cancer · 2018Review
- Bioactivities of EF24, a Novel Curcumin Analog: A Review.Frontiers in oncology · 2018Review
- A liposomal formulation of the synthetic curcumin analog EF24 (Lipo-EF24) inhibits pancreatic cancer progression: towards future combination therapies.Journal of nanobiotechnology · 2016Article
- Tracking metastatic breast cancer: the future of biology in biosensors.Medical oncology (Northwood, London, England) · 2016Review
- Monocarbonyl analogs of curcumin inhibit growth of antibiotic sensitive and resistant strains of Mycobacterium tuberculosis.European journal of medicinal chemistry · 2015Article
- Phosphorylation of Xenopus p31(comet) potentiates mitotic checkpoint exit.Cell cycle (Georgetown, Tex.) · 2015Article
- Article
- Hypersensitivity of primordial germ cells to compromised replication-associated DNA repair involves ATM-p53-p21 signaling.PLoS genetics · 2014Article
- Mouse pharmacokinetics and metabolism of the curcumin analog, 4-piperidinone,3,5-bis[(2-fluorophenyl)methylene]-acetate(3E,5E) (EF-24; NSC 716993).Cancer chemotherapy and pharmacology · 2014Article
- Novel targets for ATM-deficient malignancies.Molecular & cellular oncology · 2014Review
- Damaged mitochondria in Fanconi anemia - an isolated event or a general phenomenon?Oncoscience · 2014Article
- Monocarbonyl curcumin analogues: heterocyclic pleiotropic kinase inhibitors that mediate anticancer properties.Journal of medicinal chemistry · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe Fanconi anemia (FA) pathway is a multigene DNA damage response network implicated in the repair of DNA lesions that arise during replication or after exogenous DNA damage. The FA pathway displays synthetic lethal relationship with certain DNA repair genes such as ATM (Ataxia Telangectasia Mutated) that are frequently mutated in tumors. Thus, inhibition of FANCD2 monoubiquitylation (FANCD2-Ub), a key step in the FA pathway, might target tumor cells defective in ATM through synthetic lethal interaction. Curcumin was previously identified as a weak inhibitor of FANCD2-Ub. The aim of this study is to identify derivatives of curcumin with better activity and specificity.
resultsUsing a replication-free assay in Xenopus extracts, we screened monoketone analogs of curcumin for inhibition of FANCD2-Ub and identified analog EF24 as a strong inhibitor. Mechanistic studies suggest that EF24 targets the FA pathway through inhibition of the NF-kB pathway kinase IKK. In HeLa cells, nanomolar concentrations of EF24 inhibited hydroxyurea (HU)-induced FANCD2-Ub and foci in a cell-cycle independent manner. Survival assays revealed that EF24 specifically sensitizes FA-competent cells to the DNA crosslinking agent mitomycin C (MMC). In addition, in contrast with curcumin, ATM-deficient cells are twofold more sensitive to EF24 than matched wild-type cells, consistent with a synthetic lethal effect between FA pathway inhibition and ATM deficiency. An independent screen identified 4H-TTD, a compound structurally related to EF24 that displays similar activity in egg extracts and in cells.
conclusionsThese results suggest that monoketone analogs of curcumin are potent inhibitors of the FA pathway and constitute a promising new class of targeted anticancer compounds.
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