Quinamed (amonafide) / Teva - LARVOL DELTA

Harnessing glycolysis- and cholesterol synthesis-related genes for prognostic modeling in lung adenocarcinoma. (PubMed, Comput Methods Biomech Biomed Engin) - "Drug sensitivity analysis suggested that amonafide, AM-5992, and AZD-3147 may serve as potential therapeutic candidates. In conclusion, this model enables precise survival prediction and provides valuable insights for personalized immunotherapy and targeted treatment."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Drug repositioning for pan-cancers of the digestive system: Identification of amonafide and BX795 as potential therapeutics via integrative Omics analysis. (PubMed, PLoS One) - "Our study demonstrates the utility of drug repositioning for identifying potential therapeutics for digestive system cancers. Amonafide and BX795 emerged as promising candidates in targeting both CRC and LIHC. Further in vivo studies and clinical trials are warranted to validate these findings."

Journal • Pan tumor • Biliary Cancer • Biliary Tract Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CCNE1 • CHEK1 • NCBP2 • NXF1 • RPS27A

Topoisomerase inhibitor amonafide enhances defense responses to promote longevity in C. elegans. (PubMed, Geroscience) - "Treating a C. elegans model for Parkinson's disease with amonafide improved mobility. In conclusion, we identified amonafide as a novel geroprotector, which activates mitochondrial-, pathogen-, and xenobiotic-associated defense responses that-though more studies are needed-may serve as a candidate for Parkinson's disease therapy."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • AKT1 • ATF4

Single-cell transcriptomics analysis reveals dynamic changes and prognostic signature in tumor microenvironment of PDAC. (PubMed, Sci Rep) - "Furthermore, our analysis revealed significant interactions between cells at different stages of PDAC and identified three promising therapeutic agents (XR-11576, Ixabepilone, and AMONAFIDE) based on correlated genes. Finally, molecular docking studies validated their potential by confirming stable binding with key protein targets. This study not only provides insights into the evolving TME of PDAC but also offers a new prognostic model and potential therapeutic strategies, contributing to improved management and treatment of this aggressive cancer."

Biomarker • IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CTSD • FCGR2A • HMOX1 • HSPB1 • IFI30 • NPC2 • SEC61G • TNFRSF4 • ZFP36 • ZFP36L1

An enzyme-responsive double-locked amonafide prodrug for the treatment of glioblastoma with minimal side effects. (PubMed, Chem Sci) - "Moreover, three-dimensional multicellular U87 tumor spheroid assays and in vivo experiments confirm the potent antiproliferative activity of AcKLP against glioblastoma cells. This work demonstrates a novel de-caging strategy to improve the selectivity and efficacy of amonafide for cancer therapy."

Adverse events • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Single-cell transcriptomics reveals tumor microenvironment changes and prognostic gene signatures in hepatocellular carcinoma. (PubMed, Int Immunopharmacol) - "Cell communication analysis among tumor-infiltrating immune cells reveals significant differences in the main signaling pathways at different stages of HCC progression. Finally, drug sensitivity analysis based on key genes identifies Acetalax, Allopurinol, and Amonafide as potential candidates for HCC treatment."

Biomarker • Gene Signature • Journal • Tumor microenvironment • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • CAFs • YY1

Amonafide-based H2O2-responsive theranostic prodrugs: Exploring the correlation between H2O2 level and anticancer efficacy. (PubMed, Bioorg Chem) - "Our work broadens the range of small molecule H2O2-activated anticancer theranostic prodrugs, which are currently limited in number. We anticipate that the applications of PBA-AMF will extend to a wider spectrum of tumors and other diseases associated with increased H2O2 levels, thereby offering new horizons in cancer diagnostics and treatment."

Journal • Breast Cancer • Oncology • Solid Tumor

Design, docking optimization, and evaluation of biotin-PEG4-1,8-naphthalimide as a potent and safe antitumor agent with dual targeting of ferroptosis and DNA. (PubMed, RSC Med Chem) - "The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and MGC-803 and U251 xenograft models identified 4d as a good candidate antitumor agent with potent efficacy and safety profiles, compared with amonafide and temozolomide. Also, it could induce lipid peroxidation and thus lead to ferroptosis in MGC-803 cells, indicating that it mainly exerted antitumor effects through dual targeting of ferroptosis and DNA. These results suggested that it was feasible to design, optimize using docking simulation, and evaluate the potency and safety of biotin-PEG-1,8-naphthalimide as a antitumor agent with dual targeting of ferroptosis and DNA, based on a multi-target drug strategy."

Journal • Oncology

Rational design and synthesis of triazene-amonafide derivatives as novel potential antitumor agents causing oxidative damage towards DNA through intercalation mode. (PubMed, Bioorg Chem) - "UV-vis and fluorescence spectra, and gel electrophoresis assays were employed to further confirm the intercalation mode of D-11 (D-12) towards DNA base pairs. Moreover, D-11 was proved to exhibit stronger anti-proliferation activity than mitionafide and amonafide against both A549 and HeLa cell lines."

Journal • Oncology

Comprehensive Profiling and Therapeutic Insights into Differentially Expressed Genes in Hepatocellular Carcinoma. (PubMed, Cancers (Basel)) - "Potential therapeutic chemicals are alvocidib, AT-7519, kenpaullone, PHA-793887, JNJ-7706621, danusertibe, doxorubicin and analogues, mitoxantrone, podofilox, teniposide, and amonafide. This multi-omic study offers a comprehensive view of DEGs in HCC, shedding light on potential therapeutic targets and drug repurposing opportunities."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • AURKA • CCNB1 • CDK1 • RRM2 • TOP2A

Discovery of 4-(N-dithiobenzyl piperazine)-1,8-naphthalimide as a potent multi-target antitumor agent with good efficacy, limited toxicity, and low resistance. (PubMed, Eur J Med Chem) - "3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) results showed that compounds 5j, 5k, and 6j exhibited superior in vitro antiproliferative activity in MGC-803, HepG-2, SKOV-3, and T24 cancer cell lines and the cisplatin-resistant cell line A549/DDP. HepG-2, SKOV-3, and T24 xenograft assay results revealed that compounds 5j, 5k, and 6j exhibited good antitumor effects compared with amonafide...Results from the omics research, confocal immunofluorescence, Western blot, transmission electron microscopy, and flow cytometry indicated that compound 5j exerted antitumor effects through multiple mechanisms, including ferroptosis, autophagy, apoptosis, and cell cycle arrest. These results suggest that screening novel 1,8-naphthalimide-based antitumor agents for good efficacy, limited toxicity, and low resistance based on a multi-target drug strategy is feasible."

Journal • Oncology

Dual-Stimuli-Activatable Hybrid Prodrug for the Self-Immolative Delivery of an Anticancer Agent and Hydrogen Sulfide with Turn-on Fluorescence. (PubMed, Chemistry) - "We report herein the dual-stimuli (ROS and CA)-responsive thiocarbamate-based prodrug (AM-TCB) for the turn-on fluorogenic delivery of the naphthalimide-based anticancer agent amonafide along with the gasotransmitter hydrogen sulfide (H S)...Western blot studies further revealed the cytoprotective effects of the released H2S from AM-TCB. The present adjuvant strategy therefore would be helpful in future for ameliorating the anticancer drug-induced side-effects."

Journal • Oncology

An Outlook of the Structure Activity Relationship (SAR) of Naphthalimide Derivatives as Anticancer Agents. (PubMed, Anticancer Agents Med Chem) - "Surprisingly, some derivatives demonstrate greater activity than the reference norms, such as cisplatin, amonafide, mitonafide and others and are selective against many cell lines. The primary objective of this research is to comprehend the effects of various substitution patterns on the structure-activity relationship (SAR) of these derivatives and the instances in which they enhance or reduce this biological activity."

Journal • Oncology

Amonafide Induces HUVEC Senescence by Inhibiting Autophagy. (PubMed, Discov Med) - "We first discovered that amonafide caused normal cellular senescence in our experiments. Amonafide-induced cellular aging by inhibiting autophagy and activating the mTOR pathway. The findings may offer new strategies for managing adverse reactions to amonafide."

Journal • AMPK • CCL2 • CDKN1A • CXCL8 • IL1B • IL6 • TP53

Novel prognostic features and personalized treatment strategies for mitochondria-related genes in glioma patients. (PubMed, Front Endocrinol (Lausanne)) - "Finally, using cellMiner database and molecular docking, it was confirmed that UQCRB binds covalently to Amonafide via lysine at position 78 and threonine at position 82, while cellular assays showed that Amonafide inhibits glioma migration and invasion. Our three mitochondrial genomic composition-related features accurately predict Survival in glioma patients, and we also provide glioma chemotherapeutic agents that may be mitochondria-related targets."

Journal • Brain Cancer • CNS Tumor • Glioma • Immune Modulation • Oncology • Solid Tumor • CD8 • UQCRB

Cysteine-responsive prodrug of the anti-cancer drug amonafide: fluorogenic adjuvant drug delivery with hydrogen sulfide (HS). (PubMed, Chem Commun (Camb)) - "L-Cysteine (Cys)-responsive turn-on fluorogenic prodrug AM-ITC was developed for the adjuvant delivery of the anti-cancer drug amonafide and the gasotransmitter hydrogen sulfide (HS) in aqueous and cellular media. Considering the cytoprotective roles of HS, the present adjuvant strategy would be helpful in minimizing the anti-cancer drug-induced side-effects."

Journal • Oncology

Design, synthesis, and antitumor evaluation of morpholine substituted bisnaphthalimides as DNA targeting agents. (PubMed, Bioorg Med Chem Lett) - "Some compounds exhibited relatively good antiproliferative activity on the cell lines tested, in comparison with mitonafide and amonafide...In particular, in vivo antitumor assay results revealed that bisnaphthalimide A6 exhibited potent anticancer efficiency in an MGC-803 xenograft tumor model, in comparison with mitonafide, and had lower toxicity than mono-naphthalimide A7. In brief, the results suggested that bisnaphthalimide derivatives containing 3-nitro and 4-morpholine moieties might serve as DNA binding agents for the development of new antitumor agents."

Journal • Oncology • CDK2

Application of CYP1A2-Template System to Understand Metabolic Processes in the Safety Assessment. (PubMed, Food Saf (Tokyo)) - "Simulation experiments of a topoisomerase-targeting agent, amonafide, offered a possible new inhibitory-mechanism as Trigger-residue inactivation on human CYP1A2 Template...The mechanism was also supported on the inhibition/inactivation of two other drugs, DSP-1053 and binimetinib...These results suggest that CYP Template systems developed are effective tools to warn an appearance of unstable reactive intermediates. Our CYP-Template systems would support confident judgements in safety assessments through offering the mechanistic understandings of the metabolism."

Journal • CYP1A2

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Recent developments on 1,8-Naphthalimide moiety as potential target for anticancer agents. (PubMed, Bioorg Chem) - "Interestingly, some derivatives include enhanced activity than the reference standards like cisplatin, amonafide, mitonafide, etc., and be selective against the cell lines. Moreover, the structure-activity relationship of these variations for the resulting derivatives' anticancer properties has also been discussed. Thus, this review will be important for a wide range of researchers to design and development of various 1,8-naphthalimide derivatives with desired drug profiles."

Journal • Review • Oncology

Real-Time Multi-Photon Tracking and Bioimaging of Glycosylated Theranostic Prodrugs upon Specific Enzyme Triggered Release. (PubMed, Chemistry) - "We show that the use of endogenous enzymes for activated release of the therapeutic component can be observed, in real time, and monitored using one and two-photon bioimaging, offering unique insight into the prodrug pharmacokinetic profile. Furthermore, we demonstrate that the potent cytotoxicity of Amonafide is preserved using this targeted approach."

Journal • Oncology

Drastic Modulation of Molecular Packing and Intrinsic Dissolution Rates by Meniscus-Guided Coating of Extremely Confined Pharmaceutical Thin Films. (PubMed, ACS Appl Mater Interfaces) - "Further leveraging the order-to-disorder transition led to 2570% modulation of the IDR for amonafide. Our work demonstrates, for the first time, opportunities to largely modulate API dissolution by precisely controlling the dimensionality of thin films."

Journal • Oncology

Targeted methylation facilitates DNA double strand breaks and enhances cancer suppression: A DNA intercalating/methylating dual-action chimera Amonafidazene. (PubMed, Eur J Med Chem) - "Using this approach, we found that the chimera accumulated and was activated at the tumor sites specifically and demonstrated significantly stronger tumor suppressing activities compared to Amonafide in a xenograft model. Therefore, targeting alkylating groups to the proximity of DSB sites may become an effective approach towards enhancing anti-cancer activities of inhibitors of topoisomerases."

Journal • Oncology

A naphthalimide-polyamine conjugate preferentially accumulates in hepatic carcinoma metastases as a lysosome-targeted antimetastatic agent. (PubMed, Eur J Med Chem) - "The polyamine conjugate 13b displayed remarkably elevated anti-tumor and anti-metastatic effects (76.01% and 75.02%) than the positive control amonafide (46.91% and 55.77%) at 5 mg/kg in vivo...At last, 13b down-regulated the concentrations of Put, Spd and Spm by modulating polyamine metabolism key enzymes SSAT and PAO, which favored the suppression of fast growing tumor cells. Taken together, our study implies a promising strategy for naphthalimide conjugates to treat terminal cancer of HCC by targeting autophagy and tumor microenvironment with reduced toxicities and notable activities."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • HMGB1

A self-immolated fluorogenic agent triggered by HS exhibiting potential anti-glioblastoma activity. (PubMed, Analyst) - "Herein, a novel H2S responsive agent (SNF) containing amonafide (ANF), a self-immolative linker and a trigger group has been developed for imaging and chemotherapy in living cells...In addition, 3D multicellular U87MG tumor spheroids were used to further confirm the active drug release and high anti-proliferative activity of SNF. This approach may provide a general strategy for developing H2S-triggered prodrugs for synergic cancer therapy."

Journal • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor