Kinedak (epalrestat) / Ono Pharmaceutical - LARVOL DELTA

Epalrestat Combined With HAIC, Donafenib and Tislelizumab as First-line Treatment for Patients With Unresectable HCC and Diabetes (clinicaltrials.gov) - P2 | N=32 | Not yet recruiting | Sponsor: Haibo Shao | Initiation date: Jun 2026 ➔ Oct 2026

Trial initiation date • Diabetes • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor

Press needle combined with plum blossom needle improves diabetic peripheral neuropathy by inhibiting pro-inflammatory cytokines: a randomized controlled trial. (PubMed, Front Endocrinol (Lausanne)) - "All participants received basic treatment with oral epalrestat and mecobalamin for 6 months...Its therapeutic mechanism may involve inhibition of persistent neuroinflammatory cascades. http://itmctr.ccebtcm.org.cn, identifier ITMCTR2025000607."

Clinical • Journal • Diabetic Neuropathy • Oncology • Pain • IL1B • IL6 • TNFA

A case series study: the treatment of five PMM2-CDG patients with epalrestat (SSIEM 2026) - "Treatment with epalrestat was terminated prematurely in all patients due to the absence of subjectively perceived benefit. There were concerns about declining adherence to therapy among participants and their families. Although a longer treatment duration or higher doses might have had a positive impact on PMM2-CDG symptoms, no significant improvement was observed in this cohort at the doses and treatment duration used."

Clinical • Diabetic Neuropathy • AKR1B1 • PMM2

Design, Synthesis, In Silico ADME, Toxicity Prediction and Molecular Docking Studies of Benzimidazole-Oxadiazole Derivatives for α-Glucosidase and Aldose Reductase Pathways as Potent Anti-Diabetic Agents. (PubMed, Molecules) - "The compounds were observed to exhibit partially similar inhibitory effects to the reference drug epalrestate (IC50: 0.78 nM; KI: 0.74 ± 0.0 nM) on AR inhibition...Compounds 6a and 7e were found to have higher inhibitory activity against the α-GLY enzyme than the reference drug Acarbose (IC50: 128.4 µM; KI: 96.2 ± 5.7 µM) with KI values of 5.8 ± 0.4 and 7.9 ± 0.8 µM, respectively...Nevertheless, further pharmacological and toxicity evaluations are required to confirm their therapeutic potential. Among the tested molecules, compounds 6a and 7e may therefore be considered potential candidates for further investigation as anti-diabetic agents."

Journal • AKR1B1

Design of fluorinated triazinoindoles as highly potent and markedly selective ALR2 inhibitors: synthesis, in silico and in vitro evaluation of promising lead compounds. (PubMed, Bioorg Chem) - "Among the synthesized compounds, (8-F)OTI emerged as the most potent inhibitor with IC₅₀ of 15 nM against ALR2 and an ALR1/ALR2 selectivity factor exceeding 6667, markedly outperforming epalrestat...Computational ADMET analysis did not reveal major predicted liabilities and provided additional information for compound prioritization. Overall, this study demonstrates that strategic fluorination is an effective approach for improving the potency and selectivity and identifies (8-F)OTI as a promising lead compound for further optimization and biological evaluation."

Journal • Preclinical • Diabetes • AKR1B1

Personalized Drug Repurposing Screen Identifies Patient-Specific Therapeutic Candidates for Mucopolysaccharidosis Type IIIB. (PubMed, J Pers Med) - "Notably, four clinically approved drugs-baclofen, dextrose, epalrestat and moxifloxacin-reduced lysosomal accumulation in the index patient's cells. While we identified four promising candidates for the index patient, the lack of efficacy in a second patient cell line underscores that genetic heterogeneity may preclude a "one-size-fits-all" approach for MPSIIIB. These findings support the integration of individualized drug screening as a potential precision-medicine strategy, offering a potential path toward patient-specific therapies for rare diseases rather than traditional drug development."

Journal • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Aldose Reductase Inhibitor, Epalrestat, Suppresses Colorectal Cancer Cell Proliferation Through Complement-Dependent Cytotoxicity. (PubMed, Int J Toxicol) - "Activation of PKD by phorbol 12-myristate 13-acetate largely blocked the effect of EPA-mediated CD46 transactivation. Together, the current findings revealed a novel mechanism whereby EPA modulates CDC to inhibit the proliferation of cancer cells, broadening the pharmacological functions of EPA in anti-tumor therapy."

Journal • Colorectal Cancer • Oncology • Solid Tumor • AKR1B1 • CD46

Thiazolidinedione-triazole hybrids: design, synthesis, and biological evaluation as dual inhibitors of α-amylase and aldose reductase with antioxidant activity for antidiabetic therapy. (PubMed, Mol Divers) - "Compound 9a emerged as the most promising candidate, with AR inhibition (IC₅₀ = 0.074 µM) surpassing epalrestat (IC₅₀ = 0.107 µM) and α-AMY inhibition (IC₅₀ = 14.57 µM) exceeding acarbose (IC₅₀ = 18.24 µM). Molecular docking studies provided mechanistic insights into the binding interactions that govern the observed inhibitory activities. Collectively, these results establish 9a and 9j as promising multi-target lead candidates for the further development of antidiabetic therapeutics that simultaneously address hyperglycemia, diabetic complications, and oxidative stress."

Journal • Diabetes • Metabolic Disorders • AKR1B1

Functionalized thiazole and thiophene compounds as aldose reductase inhibitors: from rational design to biological and in silico evaluation. (PubMed, Bioorg Chem) - "A series of compounds 3, 4a-c, 8, 9a-b, 10, 12 and 13a-c were evaluated for in vitro ALR2 inhibitory activity, particularly congeners 8 and 10 demonstrated potent inhibition with IC50 values of 1.965 ± 0.185 and 2.135 ± 0.168 μM, respectively, comparable to the reference epalrestat (IC50 = 2.726 ± 0.292 μM)...Molecular docking studies suggested favorable binding interactions of compound 8 to key ALR2 active site residues, particularly Trp111, while MD simulations further supported the stability of the ALR2-8 complex. Hence, the combined biological and computational results establish compound 8 as an auspicious ALR2 candidate inhibitor with potential in vivo antioxidant activity for further development."

Journal • Diabetes • Metabolic Disorders • AKR1B1

2,3-Dihydroquinazolin-4(1H)-one derivatives as potent aldose reductase inhibitors: a combined experimental and computational study. (PubMed, Bioorg Chem) - "Among them, compound 9 demonstrated the highest potency (Ki = 0.052 μM), showing approximately 21-fold stronger activity than the reference inhibitor epalrestat (Ki = 1.124 μM)...In addition, ADME and toxicity predictions suggested that the majority of the compounds possess favorable pharmacokinetic properties and low predicted toxicity profiles. These results highlight the 2,3-dihydroquinazolin-4(1H)-one scaffold as a promising framework for the development of potent ALR2 inhibitors."

Journal • Diabetes • AKR1B1

Novel pyridazinone-based N-phenylacetamides as α-glucosidase-selective and dual α-glucosidase/aldose reductase inhibitors: Synthesis, SAR analysis, and cytotoxicity evaluation. (PubMed, Bioorg Chem) - "Compound 10 displayed the most favourable balanced profile, with Ki values of 11.68 ± 1.45 nM for α-glucosidase and 72.64 ± 2.95 nM for ALR2, outperforming acarbose and epalrestat. However, since the present study did not include profiling against other aldo-keto reductase isoforms, including AKR1B10, compound 10 should not yet be considered an AKR-selective ALR2 inhibitor. Broader AKR isoform selectivity profiling is therefore required before its further development as a therapeutically relevant lead compound."

Journal • Diabetes • Metabolic Disorders • AKR1B1 • AKR1B10

Intracellular Vesicle Transport Impairment as a Candidate Systems-Level Bottleneck in Chronic Diabetic Foot Ulcers: Network Medicine Identifies KIF13A as a Potential Therapeutic Vulnerability. (PubMed, Biomedicines) - "Epalrestat, an AKR1B1 inhibitor prioritized through recurrent AKR1B1-related drug signatures, is presented as a candidate compound for further evaluation. As the present analysis is observational and computational, the findings should be interpreted as hypothesis-generating; experimental perturbation studies and prospective clinical validation are required."

Journal • Inflammation • AKR1B1 • CLIP1 • EGF • HIF1A • KIF13A

The novel δ,γ-biscarboline derivative T2 suppresses erythroleukemia through inhibition of AKR1B1 in the fructose metabolic reprogramming. (PubMed, Chem Biol Interact) - "The well-known AKR1B1 inhibitor epalrestat was found to target this protein through binding to the same domain, but generated hydrogen bonds with the different amino acid residues (Tyr48 and His110)...T2 also downregulated FLI1 through inhibition of AKR1B1, which was in part responsible for its anti-erythroleukemia activities. Overall, this study is identified a novel compound that suppresses erythroleukemia through inhibition of AKR1B1 in the fructose metabolism reprogramming."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • AKR1B1 • FLI1

Adiposity and age-specific mortality among middle-aged Koreans in the Health Examinees Study (ECO 2026) - "The association between adiposity and mortality varies by age and sex. Among middle-aged and older populations, particularly men, low body weight may be a more significant factor in mortality than having overweight or class I obesity. Associations based on waist circumference were weaker and less consistent across age and sex groups."

Genetic Disorders • Obesity

Epalrestat repurposing for psoriasis: Targeting AKR1B10 to modulate the metabolic-immune axis via restoring retinol metabolism and suppressing IL-17 signaling. (PubMed, Int Immunopharmacol) - "Epalrestat alleviates skin inflammation by inhibiting AKR1B10 activity, thereby restoring retinol homeostasis. The subsequent suppression of the IL-17 signaling axis is more likely a downstream consequence of improved metabolic status and a remodeled inflammatory microenvironment, rather than a direct effect. These findings support Epalrestat as a potential therapeutic agent for psoriasis that concurrently modulates metabolic and inflammatory pathways."

Journal • Dermatitis • Dermatology • Immunology • Inflammation • Metabolic Disorders • Psoriasis • AKR1B10 • IL17A

Epalrestat Combined With HAIC, Donafenib and Tislelizumab as First-line Treatment for Patients With Unresectable HCC and Diabetes - A Multicenter, Prospective, Single-arm Clinical Study (clinicaltrials.gov) - P2 | N=32 | Not yet recruiting | Sponsor: Haibo Shao

New P2 trial • Diabetes • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor

Clinical Study on the Combined Use of Tadalafil and Epalrestat in the Treatment of Diabetic Neurovascular Erectile Dysfunction. (PubMed, J Mol Neurosci) - No abstract available

Journal • Erectile Dysfunction

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