Enaroy (enarodustat) / Japan Tobacco, JW Pharma, Shenzhen Salubris - LARVOL DELTA

Prolyl-hydroxylase domain inhibition enhances collagen levels in oral mucosa-derived fibroblasts. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "We examined three PHD inhibitors, IOX4, Enarodustat, and Daprodustat, for their effect on collagen levels in keratinized OMDFs. The mechanism involves HIF-1α-mediated upregulation of collagen-modifying enzymes. These findings highlight the potential of repurposing clinically approved PHD inhibitors as therapeutic agents for promoting the healing and regeneration of damaged gingiva and additional tissues."

Journal • HIF1A

Characterization of Novel Enarodustat Metabolites Using Liquid Chromatography-High Resolution Mass Spectrometry for Doping Control Purposes. (PubMed, Drug Test Anal) - "The study elucidates enarodustat's metabolic pathways and provides a foundation for developing sensitive detection methods. Future work should focus on synthesizing reference materials to identify metabolite structures."

Journal

Erythropoietin-Mimetic Peptide Pegmolesatide Therapy for Pure Red Cell Aplasia in a Patient with Nondialysis-Dependent Type 1 Diabetic Nephropathy: A Case Report (KIDNEY WEEK 2025) - "Enarodustat and roxadustat were administered successively after discontinuation of EPO, but anemia did not improve, and the patient was maintained with weekly blood transfusions...Discussion The new EPO-mimetic peptide pegmolesatide, which consists of 44 amino acids and has a completely different peptide chain structure from peginesatide and EPO (Fig 4), was independently developed in China...Thus, there is no cross-immune response between pegmolesatide and EPO. In addition, pegmolesatide rarely produces drug antibodies, attributed to the low immunogenicity.Based on these findings, we speculate that pegmolesatide can provide a safe, effective, and convenient therapeutic strategy for PRCA in Chinese patients with chronic kidney disease."

Case report • Clinical • Anemia • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Hematological Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus

Effect and Mechanism of Enarodustat on Delaying Renal Interstitial Fibrosis by Mediating Aerobic Glycolysis (KIDNEY WEEK 2025) - "After interfering with HIF expression in HK-2 cells using shRNA, supplementation with JTZ-951 did not significantly improve the above phenomena. Conclusion JTZ-951 can inhibit the excessive activation of FOXK1 and the abnormally activated glycolysis, thereby delaying the progression of renal fibrosis."

Anemia • Cardiovascular • Chronic Kidney Disease • Fibrosis • Hematological Disorders • Immunology • Nephrology • Renal Disease • Reperfusion Injury • TGFB1

Profiling Inhibitor Scaffolds for the Cancer Target Jumonji-C Domain-Containing Protein 6. (PubMed, ChemMedChem) - "By contrast, some, but not all, clinically used inhibitors of the human hypoxia-inducible factor-α prolyl hydroxylase domain-containing proteins (PHDs) efficiently inhibit isolated JMJD6, in particular Enarodustat and Desidustat. The results identify attractive scaffolds for the development of selective, cell permeable JMJD6 inhibitors and suggest that JMJD6 inhibition is a potential off-target effect of PHD inhibitors in clinical use."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Discovery of enarodustat: A HIF prolyl hydroxylase inhibitor for the treatment of renal anemia (ACS-Fall 2025) - "As a result, we succeeded in identifying compound A bearing an [1,2,4]triazolo[4,3-a]pyridine core as a lead compound. Lead optimization to improve the efficacy of EPO release in cells and in vivo by improving cell permeability led to the discovery of enarodustat, with a 5-phenethyl substituent on the triazolopyridine group, which increased hemoglobin levels with daily oral dosing in rats."

Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

CANNON: Correction of Anemia With Enarodustat in Non-dialysis Dependent Chronic Kidney Disease (clinicaltrials.gov) - P4 | N=1670 | Recruiting | Sponsor: Shanghai Zhongshan Hospital | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2024 ➔ Mar 2025

Enrollment open • Trial initiation date • Anemia • Chronic Kidney Disease • Congestive Heart Failure • Hematological Disorders • Nephrology • Renal Disease

Enarodustat Tablets at Different Initial Doses for Anemia in Non-dialysis CKD Patients (clinicaltrials.gov) - P4 | N=120 | Not yet recruiting | Sponsor: Shenzhen Salubris Pharmaceuticals Co., Ltd.

New P4 trial • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Lead Generation for a HIF Prolyl Hydroxylase Inhibitor: Discovery of (7-Hydroxy-[1,2,4]triazolo[1,5‑a]pyridine-8-carbonyl)glycine as a Lead Compound of Enarodustat. (PubMed, ACS Med Chem Lett) - "We successfully identified compound 21 bearing a [1,2,4]-triazolo-[4,3-a]-pyridine core as a lead compound. Structures of enarodustat and compound 21 differed only by the presence or absence of a phenethyl group, implying that the identification of a high-quality lead compound led to our success."

Journal • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Derivatives of the Clinically Used HIF Prolyl Hydroxylase Inhibitor Desidustat Are Efficient Inhibitors of Human γ-Butyrobetaine Hydroxylase. (PubMed, J Med Chem) - "We report that the clinically used hypoxia-inducible factor-α prolyl residue hydroxylase (PHD) inhibitors Desidustat, Enarodustat, and Vadadustat efficiently inhibit isolated recombinant BBOX, suggesting that BBOX inhibition by clinically used PHD inhibitors should be considered as a possible off-target effect. Structure-activity relationship studies on the Desidustat scaffold enabled development of potent BBOX inhibitors that manifest high levels of selectivity for BBOX inhibition over representative human 2OG oxygenases, including PHD2. The Desidustat derivatives will help to enable investigations into the biological roles of l-carnitine and the therapeutic potential of BBOX inhibition."

Journal • Cardiovascular

Pharmacokinetics, Pharmacodynamics, and Safety Evaluation of the Novel HIF-PH Inhibitor Enarodustat: An Open-Label Phase I Study in Healthy Chinese Participants. (PubMed, Clin Drug Investig) - "SAL-0951 was safe and well tolerated in healthy Chinese participants and had a linear pharmacokinetic profile. We found no ethnic differences in the pharmacokinetic characteristics of the drug between Chinese and Japanese populations."

Journal • P1 data • PK/PD data

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors for Anemia in Non-Dialysis Dependent Chronic Kidney Disease: Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Indian J Nephrol) - "The studies included roxadustat (n = 2), daprodustat (n = 3), molidustat (n = 3), vadadustat (n = 2), enarodustat (n = 1), and desidustat (n = 1). Broadly, HIF-PHI molecules exhibited little difference when compared to other alternatives like erythropoietin stimulating agents (ESAs), but the evidence is not of high certainty. Our meta-analysis provides evidence on the use of HIF-PHIs as an alternative to ESAs for anemia in NDD-CKDs."

Journal • Retrospective data • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors for Anemia in Dialysis-Dependent Chronic Kidney Disease: Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Indian J Nephrol) - "The studies included roxadustat (n = 9), daprodustat (n = 5), vadadustat (n = 2), molidustat (n = 2), enarodustat (n = 1), and desidustat (n = 1). Roxadustat increased treatment-emergent adverse events up to 6-52 weeks as compared to ESAs [OR: 1.45 (95% CI 1.08-1.96); p = 0.01; six studies; 1715 participants; moderate certainty evidence]. The study provided evidence on the use of HIF-PHIs for treating renal anemia in DD-CKD patients as an alternative to ESAs."

Journal • Retrospective data • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Enarodustat for the Treatment of Anemia in Chinese Patients with Non-Dialysis Chronic Kidney Disease: A Phase 3 Trial. (PubMed, Kidney Dis (Basel)) - "Its once-daily oral administration offers convenience that may enhance the adherence. Enarodustat shows the potential as a promising therapy for anemic patients with ND-CKD."

Journal • P3 data • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

EPO-Mimetic Peptide Pegmolesatide Therapy for Pure Red Cell Aplasia in a Patient with Non-dialysis-dependent Type 1 Diabetic Nephropathy: A Case Report. (PubMed, Kidney Med) - "Enarodustat and roxadustat were administered successively after discontinuation of EPO, but anemia did not improve, and the patient was maintained with weekly blood transfusions. Subsequently, the EPO-mimetic peptide pegmolesatide was administered, and the patient's hemoglobin started to increase after 1 week and increased from 50 g/L to 92 g/L over approximately 3 months. Based on these findings, we speculate that pegmolesatide can provide a safe, effective, and convenient therapeutic strategy for PRCA in Chinese patients with chronic kidney disease."

Journal • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Hematological Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus

Bioanalysis, Analysis, Chemistry, and Pharmacological Aspects of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors. (PubMed, Curr Top Med Chem) - "The development of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors (HIFPHIs), such as Roxadustat (ROX), Enarodustat (ENA), Desidustat (DES), Vadadustat (VAD), Molidustat (MOL), and Daprodustat (DAP), has significant effects on anemia in chronic kidney disease. Research indicates that most studies concentrate on hyphenated methodologies for drug estimation in various biological fluids. Consequently, this study assesses the biological efficacy of HIF-PHIs and elucidates the analytical methodologies currently employed for measurement across various matrices."

Journal • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

CANNON: Correction of Anemia with Enarodustat in Non-dialysis Dependent Chronic Kidney Disease (clinicaltrials.gov) - P4 | N=1670 | Not yet recruiting | Sponsor: Shanghai Zhongshan Hospital

New P4 trial • Anemia • Chronic Kidney Disease • Congestive Heart Failure • Hematological Disorders • Nephrology • Renal Disease

SAL-0951 in the Treatment of Chemotherapy-induced Anemia in Patients With Non-myeloid Malignancies (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Shenzhen Salubris Pharmaceuticals Co., Ltd.

New P2 trial • Anemia • Chemotherapy-Induced Anemia • Hematological Disorders • Oncology

Efficacy and Safety Study of SAL-0951 in the Treatment of Renal Anemia in Patients Receiving Peritoneal Dialysis (clinicaltrials.gov) - P3 | N=37 | Completed | Sponsor: Shenzhen Salubris Pharmaceuticals Co., Ltd.

New P3 trial • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Study of SAL-0951 Compared to Recombinant Human Erythropoietin in Anemic Patients Receiving Maintenance Hemodialysis (clinicaltrials.gov) - P3 | N=100 | Completed | Sponsor: Shenzhen Salubris Pharmaceuticals Co., Ltd.

New P3 trial • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Metabolomic Insights into Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors' Kidney Protection in Contrast-Induced Nephropathy (KIDNEY WEEK 2024) - "This study has clarified the biochemical changes from contrast medium and enarodustat's modulation. Enarodustat appeared to promote a metabolic shift aiding renal recovery post-CIN. Elevated metabolites related to energy and repair in Nx-E suggested enhanced AKI protection."

Acute Kidney Injury • Nephrology • Renal Disease • HIF1A

Crystallographic and Selectivity Studies on the Approved HIF Prolyl Hydroxylase Inhibitors Desidustat and Enarodustat. (PubMed, ChemMedChem) - "We obtained crystal structures of Desidustat and Enarodustat in complex with the human 2OG oxygenase factor inhibiting hypoxia-inducible factor-α (FIH), which, together with modelling studies, inform on the binding modes of Desidustat and Enarodustat to active site Fe(II) in 2OG oxygenases, including PHD1-3. The results will help in the design of selective inhibitors of both the PHDs and other 2OG oxygenases, which are of medicinal interest due to their involvement inter alia in metabolic regulation, epigenetic signalling, DNA-damage repair, and agrochemical resistance."

Journal • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease • Targeted Protein Degradation

A national, multicenter, prospective study of the efficacy and safety of enarodustat in anemic patients with CKD not requiring dialysis (ChiCTR) - P=N/A | N=160 | Recruiting | Sponsor: The First Affiliated Hospital of Wenzhou Medical University; The First Affiliated Hospital of Wenzhou Medical University

New trial • Anemia • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Hypertension • Renal Disease

Changes in Iron Markers and D-dimer Levels during Enarodustat Treatment Depends on Different Iron Prescription Patterns in Hemodialysis Patients (ERA-EDTA 2024) - "We divided the subjects into three groups according to practice patterns of iron administration: subjects who did not receive iron at all during the enarodustat administration period (Non-Iron Group), subjects who received intravenous iron at least once (IV Iron Group), and subjects who continuously received oral iron-containing preparations including ferric citrate (Oral Iron Group). These findings suggest the superiority of continuous oral iron supplementation over intermittent IV iron supplementation or no iron supplementation during HIF-PH inhibitor administration in terms of preventing thrombosis through maintaining TSAT levels. The association between iron- related parameters and the occurrence of thrombosis needs to be analyzed."

Clinical • Anemia • Cardiovascular • Hematological Disorders • Renal Disease

The comparison of four hypoxia-inducible factor prolyl hydroxylase inhibitors on drug potency and cost for treatment in patients with renal anemia. (PubMed, Clin Exp Nephrol) - "The difference in dose escalation for anemia treatment among HIF-PHIs is due to differences in drug potency, where the HPI significantly differs among HIF-PHIs. The disparity between the HPI and the cost of the initial dose accounts for the variance in the daily costs of renal anemia treatment among HIF-PHIs."

Journal • Anemia • Hematological Disorders