Kinedak (epalrestat) / Ono Pharmaceutical - LARVOL DELTA

Glycohypoxia: a hypothesis linking chronic hyperglycemia to functional hypoxia and diabetic complications in type 2 diabetes. (PubMed, Med Gas Res) - "Overall, these cascades may activate hypoxia-inducible factor-1α, elevate vascular endothelial growth factor and transforming growth factor-β, and promote fibrosis and angiogenesis, contributing to complications, such as retinopathy, neuropathy, nephropathy, cardiomyopathy, and potentially cancer, via Warburg-like metabolic shifts. Therefore, anti-glycation agents (e.g., aminoguanidine), polyol inhibitors (e.g., epalrestat), glucose transporter type 4 agonists (e.g., fisetin), and 2,3-bisphosphoglycerate enhancers can restore oxygen unloading function, improve hyperglycemia, and treat diabetes."

Journal • Cardiomyopathy • Cardiovascular • Diabetes • Fibrosis • Immunology • Metabolic Disorders • Oncology • Pain • Renal Disease • Retinal Disorders • Type 2 Diabetes Mellitus • AKR1B1 • AQP1 • HIF1A

Protection mechanism of epalrestat on glutamate-induced retinal excitotoxicity model based on network pharmacology. (PubMed, Biochem Biophys Res Commun) - "EPS inhibits retinal excitotoxicity by acting as an antioxidant and anti-inflammatory through the Nrf2/HO-1 signaling pathway. EPS may have some clinical benefits in reducing retinal excitotoxicity-related retinopathy."

Journal • Inflammation • Retinal Disorders • HMOX1 • IL1B • IL6 • TNFA

A Prospective, Single-Arm Investigator-Initiated Trial to Evaluate the Efficacy and Safety of Epalrestat Combined with Toripalimab plus Bevacizumab as First-Line Therapy for Chemotherapy-Ineligible or Chemotherapy-Intolerant Patients with Unresectable, Metastatic, Locally Advanced or Advanced Non-Small Cell Lung Cancer (ChiCTR) - P2 | N=21 | Recruiting | Sponsor: The Affiliated Hospital of Qingdao University; The Affiliated Hospital of Qingdao University

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

Clinical Applications of Data Science and Machine Learning in the Pediatric Cardiac Intensive Care Unit. (PubMed, Pediatr Cardiol) - "in Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc, 26(8):e997-e1008, 2025)...Pediatric CICU ML models exhibit high discriminative power but limited calibration, validation, and deployment evidence. Translation to safe bedside use will require multicenter waveform-rich repositories, standardized calibration reporting, interpretable model design, and prospective pragmatic trials demonstrating clinical benefit."

Journal • Review • Acute Kidney Injury • Cardiovascular • Critical care • Heart Failure • Nephrology • Pediatrics • Renal Disease

A single-arm, open-label, single-center, exploratory phase II clinical study of etoposide capsules combined with bevacizumab and avelumab in the treatment of platinum-resistant or platinum-refractory ovarian cancer (ChiCTR) - P2 | N=33 | Not yet recruiting | Sponsor: Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

New P2 trial • Platinum resistant • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • MUC16

Clinical study of dapagliflozin in Patients with diabetes mellitus complicated with peripheral neuropathy - A randomized controlled study (ChiCTR) - P=N/A | N=84 | Not yet recruiting | Sponsor: Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Chinese Medicine; Nanjing Integrated Tradit

New trial • Diabetes • Metabolic Disorders • Pain

Gemcitabine and Nab-Paclitaxel Combined With Iparomlimab-Tuvorilimab for Advanced Gallbladder Cancer (ChiCTR) - P2 | N=44 | Not yet recruiting | Sponsor: Xinhua Hospital Affiliated to Shanghai Jiaotong University of Medicine; Xinhua Hospital Affiliated to Shanghai Jiaotong University of Medicine

New P2 trial • Gallbladder Cancer • Oncology • Solid Tumor

Targeting AKR1B1 reprograms tumor-associated macrophages to enhance antitumor immunity. (PubMed, J Immunother Cancer) - "AKR1B1 as a critical regulator of TAM-mediated immunosuppression and highlight its therapeutic potential to enhance the efficacy of ICIs."

IO biomarker • Journal • Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKR1B1 • CCR5 • CD8

Thiazolidinedione-based dual inhibitors of α-amylase and aldose reductase: Design, in vitro evaluation, and in vivo hypoglycemic activity. (PubMed, Bioorg Med Chem) - "Compound 9a, containing an N-acetamide linker and a 4-fluorobenzylidene group, inhibited AR (IC₅₀ = 117.6 nM) and α-AMY (IC₅₀ = 2.2 μM), with lower IC₅₀ values than epalrestat (127 nM) and acarbose (15 μM), respectively. In a streptozotocin-induced diabetic mouse model, 9a reduced blood glucose levels by 68.4% at a dose of 50 mg/kg. These results suggest that 9a could serve as a starting point for further development of multi-target antidiabetic agents."

Journal • Preclinical • Diabetes • Metabolic Disorders • AKR1B1

Enhancing ferroptosis and inhibiting ABCB1 make the novel aldose reductase inhibitor 5F-E a promising sensitizer in liver cancer. (PubMed, Pharm Sci Adv) - "In our study, we identified a novel ARI, 5F-E, which exhibited a more potent sensitizing effect on doxorubicin (DOX) resistant HepG2 cells (HepG2/ADR) compared to epalrestat (EPA). And, 5F-E, but not EPA, was found to increase intracellular DOX accumulation by inhibiting ABCB1. Our integrated experimental approach reveals that 5F-E exhibits strong chemosensitizing effects against multidrug-resistant liver cancer, highlighting its therapeutic promise."

Journal • Liver Cancer • Oncology • Solid Tumor • ABCB1 • AKR1B1 • SLC7A11

Enhanced Ocular Delivery of Epalrestat Using Nanostructured Lipid Carrier Laden Soft Contact Lens. (PubMed, Pharmaceutics) - "The in vivo Draize test confirmed that both blank and drug-loaded contact lenses were non-irritating and biocompatible. Thus, the optimized EPL NLCs-laden contact lens demonstrated enhanced corneal permeation, prolonged drug retention, and excellent ocular safety, offering a promising advancement in the management of diabetic retinopathy by improving bioavailability, reducing dosing frequency, and enhancing therapeutic efficacy."

Journal • Diabetic Retinopathy • Retinal Disorders • AKR1B1

AARS1-mediated AKR1B10 lactylation stabilizes an aerobic glycolysis-positive feedback loop to drive lenvatinib resistance in hepatocellular carcinoma. (PubMed, Clin Transl Med) - "AKR1B10 confers lenvatinib resistance by enhancing aerobic glycolysis in HCC cells. AKR1B10 undergoes AARS1-mediated lactylation at K173, stabilizing it by antagonizing ubiquitin-proteasomal degradation. AKR1B10 promotes LDHA Y10 phosphorylation, boosting lactate production, which drives H3K18la-mediated transcriptional upregulation of LDHA, creating a feed-forward loop. Targeting AKR1B10 with epalrestat synergizes with lenvatinib to overcome resistance in preclinical models."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • AARS1 • AKR1B1 • AKR1B10 • LDHA

Targeting aldose reductase in pulmonary fibrosis: Blocking de novo fatty acid synthesis halts pro-fibrotic M2 polarization. (PubMed, Int J Biol Macromol) - "Here, we observed elevated AR expression and activity in the serum of patients with IPF and in the lungs of mice and rats with bleomycin - induced pulmonary fibrosis. Our findings indicate that AR plays a crucial role in pulmonary fibrosis by activating ERK-MYC signaling, promoting the expression of FASN and ACC1, enhancing fatty acid synthesis, and inducing macrophage M2 polarization. Notably, Epalrestat-an aldose reductase inhibitor approved by the Food and Drug Administration (FDA) for the treatment of diabetic neuropathy-exhibits potent antifibrotic effects in preclinical models, which supports its immediate clinical applicability for the repurposing of IPF treatment."

Journal • Diabetes • Diabetic Neuropathy • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Metabolic Disorders • Oncology • Pain • Pulmonary Disease • Respiratory Diseases • ACACA • AKR1B1 • FAS • FASN • IL4

A comparative study to assess two doses of a novel aldose reductase inhibitor (ARI)/Antioxidant drug candidate Cemtirestat, the current ARI drug Epalrestat, and the antioxidant Stobadine on Fructose- and Streptozotocin-Induced hepatic and pancreatic stress responses in rats. (PubMed, J Diabetes Metab Disord) - "The findings may offer valuable insights that could facilitate the development of novel ARI/AO compounds and CMTI derivatives. The online version contains supplementary material available at 10.1007/s40200-025-01723-4."

Journal • Preclinical • Diabetes • Metabolic Disorders • AKR1B1 • CASP3 • CAT • PCNA

Synthesis of new Pyridazinone derivatives and their dual inhibitory activity on aldose reductase and α-glucosidase. (PubMed, Bioorg Med Chem Lett) - "Among the tested molecules, compound 4, bearing a fluorinated thiadiazole moiety, exhibited the most potent activity with Ki values of 0.094 μM (ALR2) and 0.171 μM (α-Glu), surpassing standard inhibitors epalrestat and acarbose, respectively. These findings suggest that halogenated pyridazinone derivatives, especially fluorinated thiadiazole analogs, represent promising dual inhibitors for managing hyperglycemia and preventing diabetic complications. The dual-targeting approach demonstrated in this work offers a rational design framework for future antidiabetic drug development."

Journal • Diabetes • Metabolic Disorders • Pain • Renal Disease • Retinal Disorders • AKR1B1

C-5-Arylidene-Thiazolidine-2,4-Dione Analogs Against Aldose Reductase: Design, Synthesis, Biological Evaluation, and Computational Insights. (PubMed, Arch Pharm (Weinheim)) - "Among them, compounds 9h and 9a exhibited superior potency against aldose reductase protein with IC50 values of 0.98 and 1.05 µM, respectively, as compared with the reference drug epalrestat (IC50 value of 1.20 µM)...Predicted in silico toxicity data suggested that the synthesized compounds were inactive and nontoxic against peroxisome proliferator-activated receptor-γ protein. These finding results support the potential of thiazolidine-2,4-dione derivatives as promising AR inhibitors for managing diabetic complications."

Journal • Diabetes • Metabolic Disorders • AKR1B1

Targeting the polyol pathway in NSCLC: Trans-(±)-kusunokinin demonstrates anti-migratory and survival benefits in in vitro and in vivo models. (PubMed, Biomed Pharmacother) - "Remarkably, KU suppressed AKR1B1 and SORD expression, reduced intracellular sorbitol and fructose levels, and induced alterations in EMT-related proteins, such as ZEB1, E-cadherin, and vimentin, at a lower concentration than epalrestat (EP), a known AKR1B1 inhibitor...Collectively, these findings suggest that KU inhibits the aggressive phenotype of lung cancer by targeting the polyol pathway and modulating EMT processes. These results support its potential as a therapeutic candidate, highlighting the need for clinical evaluation in NSCLC patients."

Journal • Preclinical • Diabetes • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AKR1B1 • CDH1 • KRAS • STK11 • VIM • ZEB1

Fostering Collaborative Care in Multiple Myeloma: An Update on the Impact of Holistic Education on Decision-Making with Antibody and CAR-T Platforms (ASH 2024) - "ABSTRACT e21008)...In a meta-analysis of outcomes from the 9 activities, learning objectives were grouped by key themes, with changes in knowledge and skills averaged across them.Results : Total learners : 13,260 (including hematologist-oncologists/oncologists : 8,179; oncology nurses : 1,296). In all activities, learners' knowledge and skills improved, with increases of : 35 percentage points (ppt) in knowledge of new evidence and changing practice guidelines supporting BCMA antibody platforms in RRMM (45% to 80%); 36 ppt in skills in treatment planning and evidence-based integration of CD38 and BCMA-targeting antibodies in the management of MM (52% to 88%); 54 ppt in ability to address safety considerations related to the use of antibody therapy and BCMA immunotherapy (32% to 86%); and 58 ppt in patient interaction skills (eg, counseling, shared decision-making) when using antibody-based and CAR-T platforms (28% to 86%).Conclusions : Improvements in knowledge and..."

Hematological Malignancies • Multiple Myeloma • Oncology

Study on the efficacy and safety of Xuezhikang capsule combination with epalrestaton in treating diabetic peripheral neuropathy patients. (PubMed, Medicine (Baltimore)) - "The level was lower than before treatment and the control group, while the level of high-density lipoprotein was higher than before treatment and the control group, with a statistically significant difference (P < .05); after treatment, the Toronto Clinical Scoring System scores of both groups were lower than before treatment, and the treatment group was lower than the control group, with a statistically significant difference; after treatment, the motor conduction velocity of the median nerve and common peroneal nerve, as well as the sensory conduction velocity of the sural nerve, median nerve, and common peroneal nerve in both groups were higher than before treatment, and the treatment group was higher than the control group, with statistical significance (P < .05); logistic regression analysis showed that high HbA1c, high triglycerides, high C-reactive protein, low high-density lipoprotein, and course of disease were risk factors for diabetes peripheral..."

Journal • Retrospective data • Diabetes • Diabetic Neuropathy • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • Oncology • Pain • Type 2 Diabetes Mellitus • CRP

Rhodanine-Sulfonate hybrids targeting aldose reductase: Synthesis, in vitro inhibition, molecular docking, and cytotoxicity studies. (PubMed, Mol Divers) - "In vitro enzyme inhibition assays revealed that all compounds acted as competitive inhibitors, with several analogues, particularly compounds 6 and 8, exhibiting stronger ALR2 inhibition (Ki = 0.43 µM and 0.48 µM, respectively) than the reference drug epalrestat (Ki = 0.98 µM)...Cytotoxicity studies on L929, A549, and RG-2 cell lines revealed that most compounds were less toxic than the reference drug at lower concentrations, with compound 8 showing a promising cytotoxic profile. These findings position rhodanine-sulfonate hybrids as promising scaffolds for the development of next-generation ALR2 inhibitors for the treatment of diabetic complications."

Journal • Preclinical • Diabetes • AKR1B1

Iparomlimab and Tuvonralimab combined with irinotecan liposome is used in recurrent/metastatic nasopharyngeal carcinoma after anti-PD - (L) 1 monoclonal antibody treatment (ChiCTR) - P2 | N=36 | Not yet recruiting | Sponsor: Chongqing University Cancer Hospital; Chongqing University Cancer Hospital

New P2 trial • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

Exploring the efficacy and safety of famitinib combined with epalrestat and torivirine in the treatment of advanced and recurrent/metastatic cervical cancer (ChiCTR) - P2 | N=90 | Not yet recruiting | Sponsor: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of

New P2 trial • Cervical Cancer • Oncology • Solid Tumor • PD-L1

The role of chikungunya virus capsid-viral RNA interactions in programmed ribosomal frameshifting. (PubMed, J Virol) - "Carey, I. Akhrymuk, B. Dahal, C. L. Pinkham, et al., PLOS Pathogens 16:e1008282, 2020, https://doi.org/10.1371/journal.ppat.1008282), suggesting that capsid-mediated modulation of translation may represent a partially conserved mechanism across the alphavirus genus. By elucidating a role for capsid in PRF modulation, this study highlights a previously unrecognized layer of gene regulation in alphaviruses with broad implications for immune evasion, viral fitness, and translational control."

Journal • Chikungunya • CNS Disorders • Immunology • Infectious Disease • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Rheumatology

Oral Epalrestat Therapy in Pediatric Subjects With PMM2-CDG (clinicaltrials.gov) - P3 | N=42 | Terminated | Sponsor: Maggie's Pearl, LLC | Trial completion date: Dec 2025 ➔ Feb 2025 | Active, not recruiting ➔ Terminated; Due to futility

Trial completion date • Trial termination • Pediatrics • PMM2

Comparative efficacy of moxibustion as an add-on treatment with different durations for diabetic peripheral neuropathy: study protocol for a randomized controlled trial. (PubMed, Front Neurol) - P=N/A | "The conventional treatment group will be administered mecobalamin and epalrestat for a duration of 4 weeks, while the moxibustion groups will receive moxubustion as an add-on therapy treatment twice a week over the same period...The findings could enhance treatment efficacy, reduce adverse effects, and alleviate DPN's socio-economic burden. https://clinicaltrials.gov/, NCT06330233."

Journal • Diabetic Neuropathy • Pain • Peripheral Neuropathic Pain