Hexalen (altretamine) / Ipsen, Eisai - LARVOL DELTA

Combined use of lipid-based encapsulated altretamine nanoparticles- mediated ultrasound sonoporation therapy and catheter-based rhenium 186-mediated brachytherapy for neointimal hyperplasia regression (ISTH 2024) - "Targeting aortic stenosis with combination therapy, under ultrasound guidance was possible and appeared safe. Additionally, the treatment group's mean values for arterial mean wall thickness (MWT), percentage of luminal cross-sectional area of stenosis (LAS%), and smooth muscle hyperplasia cells density were significantly lower than other groups (p < 0.05), according to sonographic and pathological results. Conclusion(s) : Regression of neointimal hyperplasia, can be induced by the anti-proliferative effect of brachytherapy combined with the enhanced anti-proliferative effect of altretamine, induced by the enhanced sonoporation effect of focused ultrasound, brought on by the inertial cavitation effect of collapsed capsules."

Cardiovascular • Dyslipidemia

Battling colorectal cancer via s-triazine-based MMP-10/13 inhibitors armed with electrophilic warheads for concomitant ferroptosis induction; the first-in-class dual-acting agents. (PubMed, Bioorg Chem) - "s-Triazine was rationalized as the core inspired by altretamine, an FDA-approved ferroptosis inducer...The complex-induced intracellular iron overload, depleted GSH with a relative fold decrement of 0.12, consequently triggering lipid peroxidation and ferroptosis by a 3.94 relative fold increment. Collectively, 9d could be a lead for tuning MMPs selectivity and ferroptosis induction potential to maximize the benefit of such a combination."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Oncology • Solid Tumor • GPX4 • MMP10 • MMP13

A review on the research progress of traditional Chinese medicine with anti-cancer effect targeting ferroptosis. (PubMed, Chin Med) - "Several small-molecule compounds exhibit anti-tumor effects through ferroptosis, including sorafenib and altretamine, which induce ferroptosis by inhibiting System-Xc and GPX4 respectively, but many problems, such as poor druggability, still exist. In this study, we elucidated the underlying mechanisms of ferroptosis, and the anti-tumor pharmacology of TCM targeting ferroptosis including prescriptions, Chinese herbs, extracts, and natural compounds. Our findings might act as valuable reference for research on anti-tumor drugs targeting ferroptosis, especially those drugs developed from TCM."

Journal • Review • Metabolic Disorders • Oncology • ACSL4 • AIFM2 • GPX4 • SLC7A11 • TFRC

Antitumor Activity of s-Triazine Derivatives: A Systematic Review. (PubMed, Molecules) - "To date, three s-triazine derivatives, including altretamine, gedatolisib, and enasidenib, have already been approved for refractory ovarian cancer, metastatic breast cancer, and leukemia therapy, respectively, demonstrating that the s-triazine core is a useful scaffold for the discovery of novel anticancer drugs. The medicinal chemistry of s-triazine derivatives as anticancer agents was summarized, including discovery, structure optimization, and biological applications. This review will provide a reference to inspire new and original discoveries."

Journal • Review • Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor

Design, synthesis, anticancer evaluation and molecular docking studies of 1,2,3-triazole incorporated 1,3,4-oxadiazole-Triazine derivatives. (PubMed, Heliyon) - "A new library of 1,2,3-triazole-incorporated 1,3,4-oxadiazole-triazine derivatives (9a-j) was designed, synthesized, and tested in vitro for anticancer activity against PC3 and DU-145 (prostate cancer), A549 (lung cancer), and MCF-7 (breast cancer) cancer cell lines using the MTT assay with etoposide as the control drug. The compounds exhibited remarkable anticancer activity, with IC50 values ranging from 0.16 ± 0.083 μM to 11.8 ± 7.46 μM, whereas the positive control ranged from 1.97 0.45 μM to 3.08 0.135 μM. Compound 9 d with a 4-pyridyl moiety shown exceptional anticancer activity against PC3, A549, MCF-7, and DU-145 cell lines, with IC50 values of 0.17 ± 0.063 μM, 0.19 ± 0.075 μM, 0.51 ± 0.083 μM, and 0.16 ± 0.083 μM, respectively."

Journal • Breast Cancer • Genito-urinary Cancer • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor

The Combined Anti-Tumor Efficacy of Bioactive Hydroxyapatite Nanoparticles Loaded with Altretamine. (PubMed, Pharmaceutics) - "Ehrlich's ascites model in Balb/c mice showed comparable synergistic efficacy in a tumor regression trial. While the ALT-HA-NPs were able to shrink the tumor size by six times, the free ALT was only able to reduce the tumor volume by half."

Journal • Oncology

Room Temperature Dialkylamination of ChloroHeteroarenes Using Cu(II)/PTABS Catalytic System. (PubMed, Chem Asian J) - "We report herein, a highly efficient, room temperature dimethylamination of chloroheteroarenes performed via the in-situ activation of N,N-dimethylformamide (DMF). With a large substrate scope that includes, various heteroarenes, purines as well as commercially relevant drugs such as altretamine, ampyzine and puromycin precursor."

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Mode of interaction of altretamine with calf thymus DNA: biophysical insights. (PubMed, J Biomol Struct Dyn) - "The mode of binding was further confirmed by viscosity and molecular docking studies. Molecular docking further ascertained binding of altretamine in the minor groove of the CT-DNA, preferably with the A-T rich sequences."

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The mechanisms and therapeutic targets of ferroptosis in cancer. (PubMed, Expert Opin Ther Targets) - "Thus, new FINs with high selectivity and bioavailability are required to target tumor cells more specifically and potently. Particularly, the combination of FINs with chemotherapy, radiotherapy, targeted therapy, and immunotherapy warrants clinical investigation in the future."

Journal • Metabolic Disorders • Oncology

"#Hexalen?...for the pain in throat..." (@kellytsolakis)

Pain

"آلترتامین (انگلیسی: Altretamine) با نام تجاری هگزالن یک داروی شیمی‌درمانی است که توسط سازمان غذا و دارو در سال ۱۹۹۰ میلادی مورد پذیرش واقع شد..از وجود انسولین قلمی در داروخانه‌ّا اطمینان حاصل کنید@merck" (@joe56118162)

Phytochemical, acute toxicity and renal protective appraisal of Ajuga parviflora hydromethanolic leaf extract against CCl induced renal injury in rats. (PubMed, BMC Complement Med Ther) - "The restored urine and serum profile of various parameters to normal physiological levels suggests that the A. parviflora has potential antioxidant and repairing potential in renal disorders."

Journal • Preclinical • Nephrology • Renal Disease

The effect of cation-π interactions on the stability and electronic properties of anticancer drug Altretamine: a theoretical study. (PubMed, Acta Crystallogr C Struct Chem) - "There are good correlations between the achieved densities and the amounts of charge transfer with the interaction energies. Finally, the stability and reactivity of the cation-π interactions can be determined by quantum chemical computation based on the molecular orbital (MO) theory."

Journal • Oncology

Elucidating Compound Mechanism of Action by Network Perturbation Analysis. (PubMed) - "Finally, unknown-MoA compound analysis revealed altretamine, an anticancer drug, as an inhibitor of glutathione peroxidase 4 lipid repair activity, which was experimentally confirmed, thus revealing unexpected similarity to the activity of sulfasalazine. This suggests that regulatory network analysis can provide valuable mechanistic insight into the elucidation of small-molecule MoA and compound similarity."

Journal • Biosimilar • Oncology

The human gut chemical landscape predicts microbe-mediated biotransformation of foods and drugs. (PubMed, Elife) - "MicrobeFDT allows users to flexibly interrogate microbial metabolism, compounds of interest, and toxicity profiles to generate novel hypotheses of microbe-diet-drug-phenotype interactions that influence patient outcomes. We validate one such hypothesis experimentally, using MicrobeFDT to reveal unrecognized gut microbiome metabolism of the ovarian cancer drug altretamine."

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Anticancer altretamine recognition by bovine serum albumin and its role as inhibitor of fibril formation: Biophysical insights. (PubMed, Int J Biol Macromol) - "It is observed that anticancer drug altretamine can also act as an inhibitor of fibrillation in BSA and hence can be useful in the treatment of neuro-degenerative diseases. Differential scanning calorimetry has been employed to study the thermal transitions of BSA at different stages of the fibrillation process with and without altretamine to obtain insights into the extent of stabilisation provided by the drug to the protein in native, nucleation/elongation and matured state in the fibrillation process."

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Metabonomics analysis of Zi goose follicular granulosa cells using ENO1 gene expression interference. (PubMed, J Anim Physiol Anim Nutr (Berl)) - "When compared with the non-coding shRNA (NC) group, the lower level metabolites were (R)-(+)-citronellic acid, altretamine, 3-hydroxycaproic acid, heptadecanoic acid, cholecalciferol vitamin D3, indole, benzoic acid, capric acid, caffeic acid, azelaic acid, 3,4-dihydroxyhydrocinnamic acid and cholic acid, while oleic acid was detected at high levels...This observation was consistent with the metabolomics data. Through these studies, we found that decreased ENO1 levels altered certain metabolite levels in FGCs."

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