chloroquine phosphate / Generic mfg. - LARVOL DELTA

Pharmacological inhibition of USP14 attenuates LPS-induced septic myocardial injury by rebalancing Bach1/Nrf2 signalling and mitochondrial quality control. (PubMed, Int Immunopharmacol) - "USP14 inhibition attenuates LPS-induced inflammatory myocardial injury by rebalancing Bach1/Nrf2 signalling, suppressing oxidative stress, and preserving mitochondrial quality control. These findings suggest that USP14 may serve as a potential pharmacological target for septic cardiomyopathy, although the direct molecular relationship between USP14 and Bach1 requires further clarification."

Journal • Cardiomyopathy • Cardiovascular • Targeted Protein Degradation • BACH1 • BRIP1 • USP14

Synergistic Ionic Liquid-Antibiotic Combination as a Strategy against Methicillin-Resistant Staphylococcus aureus (MRSA). (PubMed, ACS Omega) - "Although the ILs displayed limited intrinsic antibacterial activity, the top candidate markedly reduced minimum inhibitory concentrations (MICs) in combination, demonstrating strong synergistic interactions with doxycycline and kanamycin (FICI = 0.29 and 0.41, respectively) and an additive interaction with chloramphenicol (FICI = 0.80). Importantly, combination treatments achieved effective bacterial eradication at reduced antibiotic doses while maintaining low cytotoxicity toward mammalian cells, thereby improving the therapeutic window. These findings establish chloroquine-derived ionic liquids as promising antibiotic adjuvants that potentiate bactericidal activity through oxidative stress amplification and membrane destabilization, offering a practical strategy to combat multidrug-resistant bacterial infections."

Journal • Infectious Disease

Manganese Dioxide Nanoparticles Protect PC12 Cells Against H2O2-Induced Oxidative Stress Injury by Regulating PI3K/Akt-Mediated Autophagy. (PubMed, Pharmaceutics) - "Further analysis showed that BSA-MnO2 NPs enhanced Akt phosphorylation, while LY294002, a PI3K inhibitor, suppressed Akt activation, disrupted autophagy regulation, and eliminated their neuroprotective effects. In contrast, chloroquine did not affect Akt phosphorylation, indicating that PI3K/Akt signaling acts upstream of autophagy regulation. Collectively, these findings demonstrate that BSA-MnO2 NPs protect PC12 cells against H2O2-induced oxidative injury by restoring autophagy through the PI3K/Akt signaling pathway, highlighting a potential role of BSA-MnO2 NPs in the treatment of oxidative-stress-related neurodegenerative disorders."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

Eugenol-based carbazole-triazole derivative 5m exhibits potent anti-plasmodial activity associated with predicted plasmepsin II binding and oxidative stress in chloroquine-resistant Plasmodium falciparum. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Derivative 5m was non-cytotoxic to Vero cells and exhibited favourable ADMET properties. Collectively, our findings substantially expand the pharmacological evaluation of compound 5m by demonstrating its activity against drug-resistant P. falciparum and providing mechanistic evidence supporting anti-plasmodial action."

Journal • Infectious Disease • Malaria

Aporphine Alkaloid N-Nornuciferine from Nelumbo nucifera Induces MAPK-Associated Autophagy Under Nutrient Deprivation in Human Pancreatic Cancer Cells. (PubMed, Pharmaceuticals (Basel)) - "Chloroquine (CQ) further increased LC3-II accumulation, particularly at 10 µM 5, compared with CQ alone... (-)-N-nornuciferine (5) exhibits anti-austere and anticancer activities in pancreatic ductal adenocarcinoma (PDAC) models, accompanied by MAPK phosphorylation and autophagy-related changes under nutrient deprivation conditions. Conventional caspase-dependent apoptosis is unlikely to be the main contributor to this process."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CASP3 • PARP1 • SQSTM1

TES2026: Ethiopian Antimalarial Therapeutic Efficacy Study 2026 (clinicaltrials.gov) - P=N/A | N=1200 | Not yet recruiting | Sponsor: Ethiopian Public Health Institute

New trial • Infectious Disease • Malaria

Intravital pH Imaging using the sensor ApHID Reveals Incomplete Lysosomal Acidification in Resident Meningeal Phagocytes. (PubMed, bioRxiv) - "Photothrombotic ischemic lesions induced progressive lysosomal acidification in local phagocytes, while acute chloroquine treatment led to rapid alkalinization. Our methodology enables direct, quantitative pH measurements without genetic manipulations, and unveils a previously unappreciated heterogeneity in lysosomal acidification among brain-resident myeloid cells."

Journal

Antiplasmodial Activity and Safety Evaluation of Three Widely Distributed Polyherbal Antimalarials in Ghana. (PubMed, J Trop Med) - "The SYBR Green fluorescence antiplasmodial assay was conducted on different stages of chloroquine-resistant and chloroquine-sensitive strains of P. falciparum...Sample C yielded an IC50 (μg/mL) value of 15.09 ± 0.319. In conclusion, the three products are antiplasmodial agents and are safe in the rodent model."

Journal • CNS Disorders • Infectious Disease • Malaria • Psychiatry • Schizophrenia

TQP: Tafenoquine Drug Levels in Small Children (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: University of Oxford

New P2 trial • Infectious Disease • Malaria

Knockdown of CDC20 attenuates pulmonary fibrosis by repressing fibroblast activation via the TSC1-mediated mTOR pathway. (PubMed, Cell Signal) - "Here, we found that the expression levels of CDC20 were upregulated in the lung tissue of mice with bleomycin (BLM)-induced pulmonary fibrosis, as well as in activated fibroblasts...Nevertheless, chloroquine (CQ)-mediated inhibition of autophagy abolished this regulatory effect on fibroblast activation...Mechanistically, CDC20 boosted the ubiquitination and degradation of TSC1, and the reduction of TSC1 promoted the activation of the mTOR pathway to inhibit fibroblast autophagy, thereby facilitating fibroblast activation. Overall, CDC20 exacerbated pulmonary fibrosis by inhibiting fibroblast autophagy via blocking the mTOR signaling pathway, which suggested that targeting CDC20 might hold putative therapeutic effect in IPF."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Targeted Protein Degradation • CDC20 • TGFB1 • TSC1

Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial. (PubMed, Nat Med) - P2 | "We subsequently tested the effects of transient versus chronic inhibition of autophagy with chloroquine or hydroxychloroquine (HCQ) and mTOR signaling with rapamycin (RAPA) or everolimus (EVE) on residual tumor cell (RTC) burden and recurrence-free survival (RFS). These findings provide proof-of-concept that targeting dormant RTCs with HCQ, EVE or their combination in breast cancer survivors or mouse models depletes minimal residual disease, warranting a definitive human randomized controlled trial. ClinicalTrials.gov registration: NCT03032406 ."

Journal • P2 data • Breast Cancer • Oncology • Solid Tumor

Effects of tetrandrine on the in vitro proliferation and differentiation of black sea bream (Acanthopagrus schlegelii) myogenic cell lines. (PubMed, Cytotechnology) - "To examine whether proteolytic or oxidative stress-related processes contributed to this phenotype, cells were co-treated with MG-132, chloroquine, or N-acetylcysteine. These findings suggest that altered depolarization-linked Ca²⁺ handling may contribute to tetrandrine-associated inhibition of myogenic differentiation in this teleost cell system. The online version contains supplementary material available at https://doi.org/10.1007/s10616-026-01061-0."

Journal • Preclinical • Myogenin • PAX7

Autophagy Inhibition Enhances the Antitumor Efficacy of MET Targeting in MET-High Pancreatic Cancer. (PubMed, Oncol Res) - "The therapeutic efficacy of combining savolitinib with the autophagy inhibitor chloroquine was further evaluated in vitro and in BxPC-3 xenograft models. Savolitinib-induced autophagy functions as an adaptive cytoprotective response in MET-high pancreatic cancer. Combined inhibition of MET and autophagy enhances antitumor activity and warrants further evaluation in MET-high pancreatic cancer models."

IO biomarker • Journal • B Cell Lymphoma • Lymphoma • Oncology • Pancreatic Cancer • Solid Tumor • BAX • CASP3

Liver Structure after Administration of Autophagy-Modifying Drugs in Mice with Experimental Skin Melanoma. (PubMed, Bull Exp Biol Med) - "Morphological changes in the liver were evaluated in mice with implanted B16 skin melanoma after chloroquine and lithium carbonate administration. Chloroquine, a well-known autophagy blocker, did not affect the development of hepatocyte degeneration and necrosis, but stimulated the cell regeneration. Collagen deposits were found in all studied groups."

Journal • Preclinical • Melanoma • Oncology • Solid Tumor

Genetic Relatedness of Cambodian Plasmodium falciparum Isolates Was Associated with Geography and Occupation. (PubMed, Am J Trop Med Hyg) - "Highly related clusters (>90% IBD) were associated with occupation, K13 mutation (C580Y versus R539T), and P. falciparum chloroquine resistance transporter mutation (P = 0.0027, 0.0001, and 0.0001, respectively)...Differences in between-province relatedness underscore how geography shapes relatedness patterns. Lower relatedness among mixed-occupation pairs compared with farmer pairs suggests occupation-associated exposure differences, with occupation potentially acting as a proxy for micro-epidemiological exposure factors such as location or behavior, highlighting the need for locally tailored interventions."

Journal

Lysosomal membrane localization of organic anion transporting polypeptide 2B1 in human hepatocytes. (PubMed, Drug Metab Dispos) - "Super-resolution imaging revealed that OATP2B1 is localized on lysosomal membranes. Both lysosomal inhibition by chloroquine in vitro and lysosomal dysfunction associated with metabolic dysfunction-associated steatohepatitis in human liver tissue increased OATP2B1 colocalization with the lysosomal membrane marker."

Journal • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • LAMP1 • SLCO2B1

Baicalin Induces Ferroptosis in Breast Cancer Through a Novel STAT3/HO-1/GPX4 Regulatory Axis. (PubMed, Phytother Res) - "The pan-caspase inhibitor Z-VAD-FMK and Fer-1 rescued BA-induced cell death, whereas necroptosis inhibitors necrosulfonamide and necroptosis inhibitor necrostatin-1 as well as autophagy inhibitor chloroquine did not exert such effects...As a natural compound modulating this ferroptosis-related axis, BA is a promising therapeutic alternative to conventional chemotherapy, which is limited by severe systemic toxicity. Collectively, this work reveals BA may regulate ferroptosis via the potential STAT3/HO-1/GPX4 signaling axis."

Journal • Breast Cancer • Oncology • Solid Tumor • GPX4 • STAT3

Gentiopicroside Regulates EGFR and Induces Its Lysosomal Degradation to Attenuate Heart Failure. (PubMed, Phytother Res) - "A pressure overload-induced cardiac remodeling model was established in C57BL/6 mice by transverse aortic constriction (TAC), followed by GPS treatment with or without the EGFR tyrosine kinase inhibitor Canertinib...GPS-induced EGFR reduction was mediated primarily through lysosomal degradation, as demonstrated by chloroquine rescue experiments, whereas proteasome inhibition had limited effects...This study identifies GPS as a regulator of EGFR stability during pathological cardiac remodeling. By promoting lysosome-dependent EGFR degradation and suppressing excessive AKT/ERK1/2 signaling, GPS attenuates cardiac hypertrophy and remodeling while preserving basal EGFR function, highlighting its potential therapeutic value for HF."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • EGFR

Design, Synthesis, and Evaluation of New 1,4-Naphthoquinone-1,2,3-triazoles as Antimalarial Agents. (PubMed, Chem Biodivers) - "To address this, the hybridization of 1,4-naphthoquinone and 1,2,3-triazole yielded a new series of compounds evaluated as prospective in vitro antimalarial agents against the chloroquine-sensitive 3D7 and chloroquine-resistant K1 strains of Plasmodium falciparum...In silico simulations of compound 9g on thirteen protein targets in P. falciparum indicated strong interactions with the 1J3 and 1LDG targets. Also, the stability of the ligand-protein complexes was verified for 3FGO."

Journal • Infectious Disease

HSP90AA1 inhibits autophagy to promote tumor growth: A novel therapeutic target in endometrial cancer. (PubMed, Cell Signal) - "HSP90AA1 drives tumor growth in endometrial cancer by suppressing autophagy via the AKT pathway. Concurrent inhibition of HSP90AA1 and activation of autophagy may offer an effective therapeutic approach."

Journal • Endometrial Cancer • Gynecology • Obstetrics • Oncology • Solid Tumor • BECN1 • CDC37 • HSP90AA1

Role of endoplasmic reticulum stress-mediated autophagy in cadmium-induced apoptosis in BRL-3A cells. (PubMed, Front Vet Sci) - "Finally, the autophagy activator rapamycin alleviated apoptosis, whereas the inhibitor chloroquine exacerbated it. In summary, our findings reveal a mechanism through which Cd coordinately regulates hepatocyte fate via ER stress-mediated, FAM134B-dependent ER-phagy and canonical autophagy, offering novel therapeutic targets and theoretical foundations for mitigating Cd toxicity."

Journal • Hepatology • Liver Failure • ATF4 • ATF6 • BECN1

Defactinib inhibits focal adhesion kinase to attenuate pancreatic cancer growth via PI3K/AKT pathway modulation. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "Notably, Defactinib also triggered ULK1-mediated compensatory protective autophagy, and co-administration with the autophagy inhibitor chloroquine effectively abrogated this process to substantially amplify the anti-tumor effect. Our findings validate PTK2 as a clinically meaningful prognostic biomarker and promising therapeutic target, providing robust new preclinical evidence to support the clinical translation of PTK2-targeted combination therapies for PC."

Journal • Oncology • Pancreatic Cancer • Solid Tumor • CASP3

Esketamine exerts a protective effect against skeletal muscle injury induced by hindlimb ischemia-reperfusion in mice by regulating autophagy. (PubMed, PLoS One) - "A mouse model of left hindlimb ischemia for 3 hours followed by 24 hours of reperfusion was established, and changes in hindlimb perfusion, functional outcomes, tissue injury, inflammatory response, and autophagy-related markers were examined after intervention with ESK alone or in combination with chloroquine phosphate (CQ). With respect to autophagy, ESK increased the microtubule-associated protein 1 light chain 3 II/I ratio while decreasing sequestosome 1 levels and the phosphorylated mechanistic target of rapamycin/total mechanistic target of rapamycin ratio; these protective effects were partially abrogated by CQ. Collectively, these findings indicate that ESK mitigates acute-phase skeletal muscle injury and improves selected early functional outcomes after lower limb ischemia-reperfusion in mice, and that its protective actions may be associated with suppression of inflammation and modulation of autophagy."

Journal • Preclinical • Cardiovascular • Oncology • Pain • Reperfusion Injury • IL6 • MAP1LC3B • mTOR • SQSTM1 • TNFA

Shikonin Attenuates Neuroinflammation and Depression-Like Behaviors by Regulating Microglial Polarization Through Inhibiting cGAS-STING/NF-κB Signaling and Lipid Droplet Accumulation. (PubMed, J Integr Neurosci) - "Our findings show that shikonin suppresses cGAS-STING activation, shifts microglia away from the M1 phenotype, and promotes autophagy, thereby reducing lipid droplet accumulation and alleviating neuroinflammation and depressive-like symptoms."

Journal • CNS Disorders • Depression • Inflammation • Major Depressive Disorder • Mental Retardation • Mood Disorders • Oncology • Psychiatry • CGAS • IL6 • STING • TNFA

Type I collagen promotes triple-negative breast cancer progression through a UBE2V1-ACSL5 regulatory axis. (PubMed, Front Oncol) - "COL I did not significantly alter ACSL5 mRNA expression by qPCR but accelerated ACSL5 protein loss; MG132, but not chloroquine, partially restored ACSL5, and total ACSL5 ubiquitination increased after COL I treatment...These findings identify a COL I-UBE2V1-ACSL5 regulatory relationship that contributes to TNBC malignant progression. The data support UBE2V1-associated regulation of proteasome-sensitive ACSL5 loss, while the complete ubiquitination machinery and the in vivo, clinical, and immune relevance remain to be defined."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Triple Negative Breast Cancer • ACSL5