meclocycline (SNX-1012) / Coserics - LARVOL DELTA

The Construction of ceRNA Regulatory Network Unraveled Prognostic Biomarkers and Repositioned Drug Candidates for the Management of Pancreatic Ductal Adenocarcinoma. (PubMed, Curr Issues Mol Biol) - "In addition to providing novel biomarkers for diagnosis that can be detected non-invasively, the secretion levels of hub genes-associated proteins were found in plasma, serum, and oral epithelium. The drug repositioning analysis revealed vorinostat, meclocycline sulfosalicylate, and trichostatin A, which exhibited significant binding affinities to the hub genes compared to their inhibitors via molecular docking analysis."

Biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • ADAM12 • ZEB2

Tetracyclines Enhance Anti-tumor T-Cell Responses Induced by a Bispecific T-Cell Engager. (PubMed, Biol Pharm Bull) - "By using bispecific T-cell engager technology to assess the cytotoxicity of peripheral T cells against tumor cells, we showed that tetracyclines (minocycline, tetracycline, doxycycline, meclocycline, chlortetracycline, and demeclocycline) enhanced T-cell cytotoxicity through granzyme B expression and CD4+ and CD8+ T-cell proliferation. In analyses of the peripheral blood mononuclear cells (PBMCs) and lung tumor-infiltrated cells of NSCLC patients, we found that demeclocycline enhanced T-cell cytotoxicity not only in PBMCs, but also in lung tumor tissues. These results support the further application of tetracyclines to combination cancer immunotherapy."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • GZMB

Boromycin has Rapid-Onset Antibiotic Activity Against Asexual and Sexual Blood Stages of Plasmodium falciparum. (PubMed, Front Cell Infect Microbiol) - "In vitro antiplasmodial activity screens of tetracyclines (omadacycline, sarecycline, methacycline, demeclocycline, lymecycline, meclocycline), macrolides (oleandomycin, boromycin, josamycin, troleandomycin), and control drugs (chloroquine, clindamycin, doxycycline, minocycline, eravacycline) revealed boromycin as highly potent against Plasmodium falciparum and the zoonotic Plasmodium knowlesi. Although there was an ionophoric activity on potassium channels, the effect was too low to explain the drug´s antiplasmodial activity. Boromycin is a promising antimalarial candidate with activity against multiple life cycle stages of the parasite."

Journal • Infectious Disease • Malaria

Identification and Ranking of Clinical Compounds with Activity against Log-phase Growing Uropathogenic Escherichia coli. (PubMed, Curr Drug Discov Technol) - "Our findings provide possible effective drug candidates for more effective treatment of antibiotic-resistant UTIs."

Clinical • Journal • Infectious Disease • Nephrology

Demeclocycline Reduces the Growth of Human Brain Tumor-Initiating Cells: Direct Activity and Through Monocytes. (PubMed, Front Immunol) - "We identified meclocycline as another activator of microglia, so we sought to test whether its better-tolerated derivative, demeclocycline, also stimulates monocytes to restrict BTIC growth...In summary, we have identified demeclocycline as a novel inhibitor of the growth of BTICs, through direct effect and through indirect stimulation of monocytes. Demeclocycline is a candidate to reactivate compromised immune cells to improve the prognosis of patients with gliomas."

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Combined effects of dissolved organic matter, pH, and divalent cations on UV-254 phototransformation of tetracycline antibiotics (ACS-Sp 2020) - "In this study, we investigated the individual and combined effects of these parameters on the photochemical properties of TCs, specifically doxycycline, meclocycline, and methacycline. Impacts of DOM and divalent cations were determined relative to these direct photolysis rate constants. Experimental results indicated that environmental factors, such as pH, DOM, and divalent cations, influenced the photodegradation of TCs in engineered processes."

Tetracyclines as Inhibitors of Pre-microRNA Maturation: A Disconnection between RNA Binding and Inhibition. (PubMed, ACS Med Chem Lett) - "In a high-throughput screening campaign, we recently discovered the rRNA-binding tetracyclines, methacycline and meclocycline, as inhibitors of Dicer-mediated processing of microRNAs...By exploring the activity of other known RNA-binding scaffolds, we identified additional disconnections between direct RNA interaction and inhibition of Dicer processing. Thus, the results presented within provide a valuable case study in the complexities of targeting RNA with small molecules, particularly with weak binding and potentially promiscuous scaffolds."

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