Musredo (molidustat) / Bayer - LARVOL DELTA

Impaired Glycolysis Leads to Defective Efferocytosis and Impaired Plaque Resolution in Tet2 Clonal Hematopoiesis. (PubMed, Circulation) - "After establishing atherosclerosis by Western diet feeding for 12 weeks in Ldlr-/- mice, Tet2 was deleted by tamoxifen injection, and hypercholesterolemia was either normalized to simulate clinical lipid management, or mice were continued on the Western diet...We linked these defects to reduced anaerobic glycolysis and lactate levels and rescued them by lactate supplementation or by treatment with the HIF-1α (hypoxia-inducible factor 1α) activator molidustat...Reduced plasma lactate levels were also shown in TET2 clonal hematopoiesis of indeterminate potential carriers in the UK Biobank. Our data identify impaired efferocytosis and glycolysis-lactate-actin polymerization pathways in advanced atherosclerosis as potential therapeutic targets to induce proresolving restructuring of the plaque immune cells and to promote beneficial atherosclerosis remodeling in subjects with TET2 CH."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Hematological Disorders • Immunology • Metabolic Disorders • Primary Immunodeficiency • HIF1A • TET2

Zhuhuang granules inhibit HIF-1α signaling to regulate oxidative stress-mitochondrial function axis to improve psoriasis. (PubMed, Tissue Cell) - "Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology, and molecular docking were combined with an imiquimod (IMQ)-induced psoriasis-like mouse model and a HaCaT cell model stimulated with an M5 cytokine cocktail (interleukin-17A, interleukin-22, oncostatin M, interleukin-1α, and tumor necrosis factor-α)...In the psoriasis mouse model, Zhuhuang granules dose-dependently alleviated erythema, scaling, and epidermal thickening, with methotrexate serving as a positive control...Molidustat attenuated these protective effects. Collectively, Zhuhuang granules ameliorate psoriasis-like alterations by suppressing HIF-1α-associated oxidative stress, inflammation, and mitochondrial dysfunction."

Journal • Dermatology • Immunology • Metabolic Disorders • Oncology • Psoriasis • CAT • HIF1A • IL17A • IL22 • TNFA

An exploratory study of the pharmacokinetics, safety, and erythropoietic effects of roxadustat in healthy cats. (PubMed, J Vet Med Sci) - "In veterinary medicine, molidustat (MOL) has demonstrated acceptable safety and efficacy with anemia of CKD in cats. In the repeated-dose study, ROX administered at 5-8 mg/kg for six weeks was not associated with apparent adverse events based on clinical condition and complete blood count. These results suggest that this dose range may serve as a candidate for future clinical evaluation in CKD cats."

Journal • PK/PD data • Hematological Disorders • Nephrology • Renal Disease

Clinically approved HIF-PHIs modulate redox metabolism, cell growth, and angiogenesis independent of HIF-1α/HIF-2α. (PubMed, Redox Biol) - "Clinically approved HIF-PHIs including roxadustat and molidustat exhibit distinct molecular structures and selectivity profiles, yet their HIF-independent effects remain poorly understood. RNA sequencing and pathway analysis revealed compound-specific off-target gene regulation affecting cellular processes beyond canonical hypoxia responses including energy metabolism and immune signaling. These findings illuminate mechanisms underlying potential adverse effects-such as thrombosis- and identify alternative therapeutic pathways, providing a framework for optimizing HIF-PHI safety profiles and expanding their clinical applications in oncology and metabolic disorders."

Journal • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Thrombosis • EPAS1 • HIF1A

Hypoxia-inducible factor prolyl hydroxylase inhibitor as a new therapeutic option for treating anemia in feline chronic kidney disease. (PubMed, Tierarztl Prax Ausg K Kleintiere Heimtiere) - "Molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), is a novel oral drug stimulating endogenous erythropoietin synthesis...Regular monitoring following the International Renal Interest Society (IRIS) guidelines is essential to keep PCV within the target range and to determine when treatment should be started, stopped, or restarted. Moreover, monitoring the iron status is important since both functional and absolute iron deficiency might be seen in cats with CKD and can impair response to treatment."

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

Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors on lipid profiles in patients with chronic kidney disease: a systematic review and meta-analysis. (PubMed, Eur J Clin Pharmacol) - "Roxadustat showed the most substantial lipid-lowering effects, while desidustat showed significant reductions in LDL-C and total cholesterol but no significant effects on triglycerides or HDL-C, and molidustat showed no significant effects. Despite these changes in lipid profiles, no significant differences in cardiovascular outcomes were observed for these three HIF-PHIs, compared with ESAs or placebo."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Hematological Disorders • Myocardial Infarction • Nephrology • Renal Disease

Hydroxylation of the HIV-1 antisense protein promotes immune evasion of HIV-1 via modulation of TBK1. (PubMed, Nat Commun) - "Here we show that the HIV-1 antisense protein (ASP) evades host immunity by interfering with the type I interferon (IFN-I) response...In humanized mice, either ASP deletion or treatment with the RNF114 inhibitor EN219 or the PHD3 inhibitor Molidustat enhances antiviral immunity and reduces viral replication. Clinically, RNF114 and PHD3 transcript levels exhibit a positive correlation with viral load in treatment-naive patients. Here we show a distinct HIV-1 immune evasion mechanism involving proline hydroxylation and K6-linked ubiquitination, highlighting therapeutic potential."

Journal • Human Immunodeficiency Virus • Infectious Disease • Targeted Protein Degradation • RNF114

Effectiveness and long-term safety of repeated oral administrations of molidustat in the management of anemia associated with chronic kidney disease in cats. (PubMed, J Vet Intern Med) - "Molidustat significantly increased HCT values in treated cats compared to CP cats. Repeated 28-day treatment cycles were well-tolerated. Molidustat is an effective and safe treatment for long-term management of anemia in cats with CKD."

Journal • Anemia • Hematological Disorders • Nephrology • Renal Disease

Phase Ib/II study with PHD inhibitor molidustat in combination with the IDH1 inhibitor ivosidenib for patients with IDH1-mutated relapsed or refractory acute myeloid leukemia (MOLIVO trial) (DKK 2026) - No abstract available

Clinical • Combination therapy • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • IDH1

EXPRESS: Palatability of sunflower oil-based versus aqueous verum formulations of molidustat in healthy cats. (PubMed, J Feline Med Surg) - "In contrast, almost no voluntary intake, even when cats were encouraged, was observed for the aqueous suspension of molidustat (Group 2).Conclusions and relevanceThis study demonstrated that molidustat in a sunflower oil-based suspension was very palatable to healthy cats. In contrast, the aqueous formulation was clearly unpalatable."

Journal

Comparative effectiveness of darbepoetin vs other agents in chronic kidney disease-related anemia: a systematic review and network meta-analysis. (PubMed, BMC Nephrol) - "Daprodustat and roxadustat indicated equivalent or higher efficacy when compared to darbepoetin in elevating hemoglobin levels in CKD-related anemia, with daprodustat demonstrating a good safety profile. While conventional ESAs remain beneficial, HIF-PHIs offer promising oral alternatives with possible benefits in cardiovascular safety and decreased hypertension risk. Further head-to-head trials are necessary to confirm these findings and guide individualized treatment strategies."

Clinical • HEOR • Journal • Retrospective data • Review • Anemia • Cardiovascular • Chronic Kidney Disease • Diabetes • Hematological Disorders • Hypertension • Metabolic Disorders • Nephrology • Renal Disease

Darbepoetin vs. Other Agents in CKD Anemia: A Meta-Analysis (KIDNEY WEEK 2025) - "Results Molidustat showed the best cardiovascular and thrombotic safety despite lower efficacy, while methyl polyethylene glycol-epoetin beta showed the largest Hb increase in this network meta-analysis of 12 randomized trials involving over 4,000 CKD patients with anemia...Conclusion Daprodustat and roxadustat indicated equivalent or higher efficacy when compared to darbepoetin in elevating hemoglobin levels in CKD-related anemia, with daprodustat demonstrating a good safety profile...Comparitive efficacy of ESAs + Lower rank number = greater hgb-raising efficacy. * Comparison only, not an exact quantitative ranking."

Retrospective data • Anemia • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Hypertension • Nephrology • Renal Disease

Clinical therapeutics in feline medicine: updates for old and new drugs. (PubMed, J Feline Med Surg) - "The clinical use of these agents, available pharmacokinetic and pharmacodynamic data, and reported adverse effects in cats are presented. The information in this article is relevant to all veterinarians who practice feline medicine."

Journal • Review

Light-driven biosensor for the rapid and selective detection of hypoxia-inducible factor-prolyl hydroxylase domain inhibitors in aqueous media and saliva. (PubMed, Mikrochim Acta) - "HIF inhibitors such as Molidustat and Vadadustat are used as doping agents in racing sports. The new materials were also utilised for the rapid screening of HIF-PHI in spiked saliva samples. The new materials and light-driven surface functionalisation process can be easily adopted to develop new screening methods for multiple biomolecules (e.g. drugs, proteins, disease biomarkers, environmental toxins) for many applications (e.g. therapeutic drug monitoring, doping control, clinical diagnostics environmental monitoring)."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Discovery and characterization of a novel HIF-2α agonist for the treatment of CKD-related renal anemia. (PubMed, Acta Pharmacol Sin) - "In zebrafish (Danio rerio), AT-1 (10 or 50 μM) exhibited favorable safety profiles and, when combined with the prolyl hydroxylase (PHD) inhibitor Molidustat (10 μM), effectively mitigated doxorubicin-induced anemia. In adenine-induced chronic kidney disease (CKD) mouse model, combined administration of AT-1 (50 mg·kg-1·d-1, i.p.) and Molidustat (10 mg·kg-1·d-1, i.p.) for 15 days produced stronger effects on increasing EPO levels and alleviating anemia than Molidustat alone, further supporting the therapeutic potential of AT-1 in CKD-related anemia."

Journal • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease • ARNT • EPAS1

In Vitro and Ex Vivo Evidences that Pharmacological Induction of the Hypoxia Response Pathway Efficiently Restricts Measles and Nipah Virus Infections. (PubMed, Emerg Microbes Infect) - "A similar antiviral effect was observed with Roxadustat and Daprodustat, two PHD enzyme inhibitors chemically unrelated to Molidustat. Finally, we showed that Molidustat inhibits NiV infection in organotypic cultures of hamster cerebellum and lung, thereby validating its effect in the two organs mainly targeted during infection. Taken together, our results provide evidence that pharmacological activation of the hypoxia-response pathway restricts MeV and NiV infections, highlighting HIF-inducing drugs as promising candidates to consider in the development of treatments."

Journal • Preclinical • CNS Disorders • Infectious Disease • Measles • Respiratory Diseases

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

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

A Study to Learn More About the Long-term Safety and Effectiveness of Molidustat as a Treatment for Japanese Men and Women With Renal Anemia (clinicaltrials.gov) - P=N/A | N=1081 | Active, not recruiting | Sponsor: Bayer | Recruiting ➔ Active, not recruiting

Enrollment closed • Anemia • Hematological Disorders

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors as a New Treatment Option for Anemia in Chronic Kidney Disease. (PubMed, Biomedicines) - "Clinical studies have shown that the hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) covered in this manuscript-roxadustat, vadadustat, daprodustat, and molidustat-effectively increase hemoglobin (Hb) levels in both non-dialyzed and dialyzed CKD patients. and retinopathy. More extensive and long-term clinical trials of HIF-PHIs-based anemia treatment in CKD patients are needed, and their results will indicate whether HIF-PHIs represent an effective and safe alternative to EPO and iron supplementation for anemia treatment in CKD patients."

Journal • Review • Anemia • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Nephrology • Oncology • Renal Disease • Retinal Disorders

Pharmacological induction of the hypoxia response pathway in Huh7 hepatoma cells limits proliferation but increases resilience under metabolic stress. (PubMed, Cell Mol Life Sci) - "This was accompanied by a higher resistance to the inhibition of mitochondrial respiration by antimycin A, a phenotype confirmed in Roxadustat-treated Huh7 cells and Molidustat-treated hepatoblastoma cells (Huh6 and HepG2). Overall, this study shows that HIF-inducing drugs increase the metabolic resilience of liver cancer cells to metabolic stressors, arguing for careful monitoring of patients treated with HIF-inducing drugs, especially when they are at risk of liver cancer."

Journal • Gastrointestinal Cancer • Hematological Disorders • Hepatoblastoma • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • EPAS1 • HIF1A • LDHA • SERPINE1

Simultaneous detection of three hypoxia-inducible factor stabilizers-molidustat, roxadustat, and vadadustat-in multiple keratinized matrices and its application in a doping context. (PubMed, Drug Test Anal) - "Limits of quantification were 2, 0.5, and 5 pg/mg for molidustat, roxadustat, and vadadustat, respectively. The analysis of the athlete's head hair (collected 1 month after the urine test) showed a concentration of molidustat of 135 pg/mg, and his beard hair and his fingernails clippings contained 55 and 40 pg/mg, respectively."

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

A Prospective Randomized Controlled Clinical Study to Investigate the Efficacy and Safety of Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitors in Non-Dialysis Patients with Chronic Heart Failure and Renal Anemia Switched from Continuous Erythropoietin Receptor Activator Treatment. (PubMed, J Clin Med) - " Forty patients were randomized by the envelop method to receive treatment with roxadustat, daprodustat, vadadustat, or molidustat. The individual HIF-PH inhibitors appear to have different effects on anemia and thyroid function. However, because this was a single-center study with a limited sample size, the efficacy and potential limitations of HIF-PH inhibitors need to be further clarified."

Journal • Anemia • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Hematological Disorders • Nephrology • 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