Bredinin (mizoribine) / Asahi Kasei, Lee's Pharm - LARVOL DELTA

A Retrospective Study on the Efficacy and Safety of Mizoribine in Anti-Rejection Therapy for Renal Transplant Recipients (ChiCTR) - P=N/A | N=200 | Not yet recruiting | Sponsor: West China Hospital, Sichuan University; West China Hospital, Sichuan University

New trial • Transplantation

Efficacy and safety of initial administration of mizoribine in deceased donor kidney transplant recipients: a Chinese single-center, prospective, randomized controlled study (ChiCTR) - P4 | N=202 | Not yet recruiting | Sponsor: The Second Affiliated Hospital of Guangxi Medical University; The Second Affiliated Hospital of Guangxi Medical University

New P4 trial • Nephrology • Transplantation

Efficacy and Safety of Conversion from Mycophenolate Mofetil to Mizoribine in Kidney Transplant Recipients with BK Polyomavirus Nephropathy (WTC 2025) - "Conversion from MMF to MZR can achieve rapid viral clearance and histological remission. This strategy maintains the stability of serum creatinine and uric acid levels with a favorable safety profile, representing a viable therapeutic option for BKPyVN."

Clinical • Renal Disease • Transplantation

Formononetin and mizoribine inhibit Porcine Reproductive and Respiratory Syndrome Virus replication in vitro. (PubMed, Front Nutr) - "Noteworthy was the observation of their synergistic effects when combined with Ribavirin. These results position FMN and MZR as promising antiviral agents against PRRSV, underscoring their low cytotoxicity and efficacy in early-stage viral inhibition. Such findings pave the way for their potential inclusion in future PRRSV management strategies."

Journal • Preclinical • Infectious Disease • Respiratory Diseases

Clinicopathological features of familial fibronectin glomerulopathy caused by a splice site variant in the Fibronectin 1 gene: a case report. (PubMed, CEN Case Rep) - "Treatment with glucocorticoids, combined with the immunosuppressant mizoribine and an angiotensin II receptor blocker (ARB), resulted in an incomplete remission of nephrotic syndrome; however, renal function has been preserved...Due to the administration of azathioprine, aspirin, and ARB, renal function and proteinuria have been stable over 10 years. The kidney biopsy revealed MPGN-like histological features in both the mother and the daughter; however, the mesangial area exhibited a milder expansion in the mother than in the daughter. Accumulating genotype-phenotype correlation data will be essential for managing FNG."

Journal • Genetic Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Rare Diseases • Renal Disease • FN1 • NECTIN1

Mizoribine or Cyclophosphamide for Lupus Nephritis: A Randomized Clinical Trial. (PubMed, JAMA Netw Open) - P3 | "Mizoribine can be used as an alternative to intravenous cyclophosphamide as induction therapy for lupus nephritis. ClinicalTrials.gov Identifier: NCT02256150."

Clinical • Journal • Glomerulonephritis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Respiratory Diseases • Systemic Lupus Erythematosus

Efficacy and safety of new combination therapy with prednisolone, mizoribine, and lisinopril for severe childhood IgA Nephropathy (IPNA 2025) - "In our previous randomized control trial, combination treatment including prednisolone (PSL) and mizoribine (MZB) with warfarin and dipyridamole may be better for severe cIgAN than the combination treatment including PSL and MZB without warfarin nor dipyridamole from the point of proteinuria remission. Conclusions We confirmed the usefulness of the new combination treatment with PSL, MZB, and lisinopril for severe cIgAN in achieving early proteinuria remission and shortening PSL use without changing the proteinuria recurrence rate. Long-term outcomes will be needed for further investigation."

Clinical • Combination therapy • Glomerulonephritis • IgA Nephropathy • Renal Disease

Systemic inhibition of de novo purine biosynthesis prevents weight gain and improves metabolic health by increasing thermogenesis and decreasing food intake. (PubMed, bioRxiv) - "Crucially, given that many purine inhibitors have been FDA-approved for use in treating various conditions, our results indicate that they may benefit overweight or obese patients. A purine biosynthesis inhibitor, mizoribine, protects against diet-induced weight gainMizoribine prevents fat mass gain in high-fat diet-fed male miceMizoribine reduces food intake and increases thermogenesisMizoribine induces expression of sarcolipin, a regulator of thermogenesisMizoribine treatment reduces ectopic lipids and increases glucose tolerance."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Oncology • Type 2 Diabetes Mellitus

An Alternatively Spliced Gain-of-Function NT5C2 Isoform Contributes to Chemoresistance in Acute Lymphoblastic Leukemia. (PubMed, Cancer Res) - "Incorporation of the 8-amino acid sequence SQVAVQKR into this enzyme created a putative phosphorylation site and resulted in elevated nucleosidase activity, which is a known consequence of gain-of-function mutations in NT5C2 and a common determinant of 6-mercaptopurine (6-MP) resistance. Furthermore, both the NT5C2ex6a and R238W variants induced collateral sensitivity to the inosine monophosphate dehydrogenase (IMPDH) inhibitor mizoribine. These results ascribe an important role for splicing perturbations in chemotherapy resistance in relapsed B-ALL and suggest that IMPDH inhibitors, including the commonly used immunosuppressive agent mycophenolate mofetil, could be a valuable therapeutic option for treating thiopurine-resistant leukemias."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • NT5C2

An Alternatively Spliced Gain-of-Function NT5C2 Isoform Contributes to Chemoresistance in Acute Lymphoblastic Leukemia. (PubMed, bioRxiv) - "Incorporation of the 8-amino acid sequence SQVAVQKR into this enzyme created a putative phosphorylation site and resulted in elevated nucleosidase activity, which is a known consequence of gain-of-function mutations in NT5C2 and a common determinant of 6-mercaptopurine (6-MP) resistance. Furthermore, both the NT5C2ex6a and R238W variants induced collateral sensitivity to the inosine monophosphate dehydrogenase (IMPDH) inhibitor mizoribine. These results ascribe an important role for splicing perturbations in chemotherapy resistance in relapsed B-ALL and suggest that IMPDH inhibitors, including the commonly used immunosuppressive agent mycophenolate mofetil, could be a valuable therapeutic option for treating thiopurine-resistant leukemias."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • NT5C2

A case of membranous nephropathy complicated by Cronkhite-Canada syndrome successfully treated with mizoribine. (PubMed, CEN Case Rep) - "Nephrotic-range proteinuria persisted despite treatment with prednisolone and cyclosporine. Additional treatment with mizoribine resulted in incomplete remission type 1 of nephrotic syndrome, suggesting that mizoribine may be a treatment option for patients with CCS with steroid-resistant MN. Considering a high prevalence of hypoproteinemia due to chronic diarrhea and protein-losing enteropathy in patients with CCS, proteinuria might be overlooked; thus, follow-up urinalysis would be recommended in patients with CCS."

Journal • Alopecia • Gastrointestinal Disorder • Genetic Disorders • Glomerulonephritis • Nephrology • Oncology • Renal Disease • Solid Tumor

Mizoribine Promotes Molecular Chaperone HSP60/HSP10 Complex Formation. (PubMed, Int J Mol Sci) - "On the other hand, high concentrations of Mizoribine promoted HSP60-HSP10 complex formation and consequently suppressed IL-6 expression. Here, we propose a novel mechanism of immunosuppressive action of Mizoribine."

Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Rheumatoid Arthritis • Rheumatology • Transplantation • HSPD1 • IL6

POWER DOPPLER AND GREYSCALE CHANGES ON SALIVARY GLAND ULTRASONOGRAPHY IN SJOGREN'S DISEASE: AN OBSERVATIONAL STUDY (EULAR 2024) - "Ninety patients (61%) received immunosuppressants (including mizoribine [42 patients], glucocorticoids [42 patients], hydroxychloroquine [28 patients], abatacept [14 patients], etc.) for over four months, 33 received Japanese-Kampo medicine, five received saliva secretion stimulants, and 35 received no medication. GS scores worsened, but SMG PD scores decreased over time in SjD patients. PDs correlated with ESSDAI, SSFR, SWE, and SWV. PDs presence suggests the possibility of future salivary gland structural changes."

Clinical • Observational data • Immunology • Inflammation • Rheumatology • Sjogren's Syndrome

Safety and Efficacy of Mycophenolate Mofetil Associated With Tacrolimus for Kidney-pancreas and Kidney Transplantation: A Systematic Review and Meta-Analysis of Randomized Studies. (PubMed, Transplant Proc) - "Gastrointestinal and hematological adverse events and infections are the most common with TAC+MMF for kidney-pancreas and kidney. TAC+MMF effectively prevents acute cellular rejection, and alternatives with AZA, CyA, SRL, ECMPS, EVL, MAN, and MSR have similar efficacy and safety profiles. TAC monotherapy and MZR may be associated with a lower risk of infections."

Clinical • Journal • Retrospective data • Review • Cytomegalovirus Infection • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Leukopenia • Transplant Rejection • Transplantation

Immunosuppressive therapy for IgA nephropathy in children. (PubMed, Cochrane Database Syst Rev) - "There is a lack of high-quality evidence to guide the management of IgAN in children. There is no evidence to indicate that steroids, other immunosuppressive therapies, or tonsillectomy, when added to optimal supportive care, prevent a decline in eGFR or proteinuria in children with IgAN. Available studies were few, with small numbers, low-quality evidence, high or uncertain risk of bias, did not systematically assess harms associated with treatment, or report net benefits or harms. Severe cases and atypical presentations of IgAN were not included in the reviewed studies, and our findings cannot be generalised to these situations."

Clinical • Journal • Review • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease • Transplantation

Approaches Towards Better Immunosuppressive Agents. (PubMed, Curr Top Med Chem) - "Derivatives of mycophenolic acid, corticosteroids and chemotherapeutics bearing heterocyclic moieties like methotrexate, azathioprine, mizoribine, and ruxolitinib are active substances with investigated mechanisms of action. In this review article, we present the synthesis of the designed chemical structures based on recent literature reports concerning novel compounds as promising immunosuppressive drugs. Moreover, some of the discussed derivers revealed also other types of activities with prospective medicinal potential."

Journal • Immunology • Transplantation

A Case Report of the Ascending Colon Cancer with Bullous Pemphigoid (PubMed, Gan To Kagaku Ryoho) - "The patient had progressive anemia while taking 10 mg/day of prednisolone and 100 mg/day of mizoribine orally for bullous pemphigoid, a colonoscopy diagnosed ascending colon cancer...Histopathological examination revealed pT3N0M0, pStage Ⅱa. In the present report, we describe a case of the ascending colon cancer with bullous pemphigoid, and discuss the case with a review of the literature."

Journal • Bullous Pemphigoid • Colon Cancer • Colorectal Cancer • Dermatology • Dermatopathology • Gastrointestinal Cancer • Hematological Disorders • Immunology • Oncology • Solid Tumor

Acute renal failure after kidney transplantation due to mizoribine-induced ureteral stones. (PubMed, BMC Nephrol) - "By analyze our case report, it shows that acute renal failure with ureteral stones after kidney transplantation can caused by MZR. Urinary alkalinization for MZR induced uric acid stones is simple and effective."

Journal • Acute Kidney Injury • Renal Calculi • Renal Disease • Transplantation • Urology

Comparative Efficacy of Mizoribine With Mycophenolate Mofetil for Living Related Kidney Transplantation Recipients (clinicaltrials.gov) - P4 | N=152 | Recruiting | Sponsor: Lee's Pharmaceutical Limited

New P4 trial • Transplantation

Synthesis of mizoribine prodrugs and their in vivo evaluation as immunosuppressive agents. (PubMed, Bioorg Med Chem Lett) - "Moreover, these prodrugs were able to prolong graft survival, when evaluated in a mouse model of cardiac allograft transplantation. Strikingly, a combination therapy of these mizoribine prodrugs with tacrolimus had a synergistic in vivo effect."

Journal • Preclinical • Cardiovascular • Transplantation • IL2

Secondary immunoglobulin A nephropathy with gross hematuria leading to rapidly progressive glomerulonephritis following severe acute respiratory syndrome coronavirus 2 vaccination: a case report. (PubMed, BMC Nephrol) - "SARS-CoV-2 mRNA vaccines activate T cells, which are involved in the pathophysiology of IgA nephropathy. Therefore, this case suggests that the exacerbation of IgA nephropathy by the vaccine favors the vasculitis aspect of the disease."

Journal • CNS Disorders • Fibrosis • Glomerulonephritis • Hepatic Encephalopathy • Hepatology • IgA Nephropathy • Immunology • Infectious Disease • Liver Cirrhosis • Lupus Nephritis • Nephrology • Novel Coronavirus Disease • Otorhinolaryngology • Renal Disease • Respiratory Diseases • Vasculitis

Demographics and treatment of patients with primary membranoproliferative glomerulonephritis in Japan using a national registry of clinical personal records. (PubMed, Clin Exp Nephrol) - "The national registry of clinical personal records of primary MPGN could provide an informative insight into the characteristics, clinical features, and treatment approaches for patients with primary MPGN in Japan."

Journal • Chronic Kidney Disease • Glomerulonephritis • Lupus Nephritis • Nephrology • Renal Disease

Long-term outcome of combination therapy with corticosteroids, mizoribine and RAS inhibitors as initial therapy for severe childhood IgA vasculitis with nephritis. (PubMed, Pediatr Nephrol) - "Combination therapy provided good kidney outcomes for Japanese children with severe IgAVN. Even including recurrent cases, the degree of proteinuria was slight, and kidney function was good at the last follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information."

Combination therapy • Journal • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease • Vasculitis

Differences in response to treatment in children with severe IgA nephropathy according to patient age. (PubMed, Fukushima J Med Sci) - "Patients aged 14 years and older with IgAN may respond poorly to treatment compared with those younger than 14 years old. Therefore, care must be taken regarding response to treatment and relapse when treating older children."

Journal • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

Management of IgAN and IgAV (KSN 2023) - "Based on the results of clinical trials, a 2-year combination therapy including prednisolone, mizoribine, and lisinopril for patients with severe childhood IgAN showing diffuse mesangial proliferation (WHO), and 2-year lisinopril for mild cases are recommended in the treatment guidelines 2020 for childhood IgAN by the Japanese society for pediatric nephrology. Severe IgAVN cases are defined as ISKDC classification grade IIIb–V and/or serum Alb < 2.5 g/dL, and receive treatment with combination therapy (previously: prednisolone, mizoribine/azathioprine, warfarin, and dipyridamole; recently: prednisolone, mizoribine, and RAS inhibitors) similar to the treatment for the patients with severe IgAN, with good outcomes. In this session, I would like to talk about the clinicopathological characteristics and present clinical situations of IgAN and IgAVN in Japan."

Glomerulonephritis • IgA Nephropathy • Immunology • Lupus Nephritis • Musculoskeletal Pain • Pain • Pediatrics • Rheumatology • Vasculitis