Delving into the Latest Updates on Mizoribine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Mizoribine (JP17/INN)

+ [3]

Target

IMPDH

Mechanism

IMPDH inhibitors(Inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors)

Therapeutic Areas

Immune System DiseasesSkin and Musculoskeletal DiseasesUrogenital Diseases

Active Indication

Nephrotic SyndromeRheumatoid ArthritisLupus Nephritis+ [1]

Inactive Indication-

Originator Organization

Asahi Kasei Corp.

Active Organization

Asahi Kasei Corp.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

JP (15 Feb 1984),

Renal transplant rejection

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC9H13N3O6

InChIKeyHZQDCMWJEBCWBR-UUOKFMHZSA-N

CAS Registry50924-49-7

This prospective, randomized controlled study is intended to enroll 152 patients in the early stages of donor kidney transplantation at six clinical centers in China between January 2023 and January 2024. All patients meeting the inclusion criteria were randomly assigned 1:1 to either Mizoribine or Mycophenolate Mofetil for 12 months. At the baseline of follow-up (before enrollment) and each follow-up point, all clinical indicators of patients were recorded to measure the therapeutic effect.

Start Date01 Jan 2023

Sponsor / Collaborator

Lee's Pharmaceutical Holdings Ltd.

NCT05293704

/ Unknown statusPhase 4

An Open Study on the Preventive Effect of Early Mizoribine Conversion on BKV Nephropathy in Renal Transplant Recipients

This study is divided into two parts: ① Part I was a retrospective observational study. Kidney transplant recipients infected with BK virus (BKV) in the First Affiliated Hospital of Sun Yat-sen University from 2015 to 2021 were retrospectively collected and divided into case group and control group whether to convert MPA drug to mizoribine. ② The second part was a prospective, open and interventional clinical trial. Thirty patients with positive urinary BK virus after kidney transplantation using Mycophenolic acid (MPA) were enrolled in the First Affiliated Hospital of Sun Yat-sen University. All patients who met the inclusion criteria were treated with mizoribine to place MPA (Mycophenolate or mycophenolate sodium enteric coated tablets) for 12 months as directed. At the baseline of follow-up (before enrollment) and at each follow-up point, clinical indicators of patients were recorded, and renal biopsy was performed to evaluate the occurrence of BKV nephropathy in patients with persistent elevated BK viruria or persistent BK viremia after conversion and patients with BK viruria after 12 months, and to judge the progress after early activation of BKV and the safety of mizoribine.

Start Date01 May 2022

Sponsor / Collaborator

Lee's Pharmaceutical Holdings Ltd.

JPRN-jRCTs051200070

/ CompletedPhase 2IIT

Efficacy of mizoribine after two years of cyclosporine treatment for children with frequently relapsing nephrotic syndrome

Start Date23 Dec 2020

Sponsor / Collaborator-

100 Clinical Results associated with Mizoribine

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100 Translational Medicine associated with Mizoribine

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100 Patents (Medical) associated with Mizoribine

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710

Literatures (Medical) associated with Mizoribine

15 Oct 2024·Cancer Research

An Alternatively Spliced Gain-of-Function NT5C2 Isoform Contributes to Chemoresistance in Acute Lymphoblastic Leukemia

Article

Author: Sehgal, Priyanka ; Ferrando, Adolfo ; Radens, Caleb M. ; Quesnel-Vallières, Mathieu ; Thomas-Tikhonenko, Andrei ; Torres-Diz, Manuel ; Reglero, Clara ; Barash, Yoseph ; Falkenstein, Catherine D. ; Tasian, Sarah K. ; Castro, Annette ; Hayer, Katharina E. ; Ang, Zhiwei ; Li, Marilyn M.

AbstractRelapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) is a major cause of pediatric cancer–related deaths. Relapse-specific mutations do not account for all chemotherapy failures in B-ALL patients, suggesting additional mechanisms of resistance. By mining RNA sequencing datasets of paired diagnostic/relapse pediatric B-ALL samples, we discovered pervasive alternative splicing (AS) patterns linked to relapse and affecting drivers of resistance to glucocorticoids, antifolates, and thiopurines. Most splicing variations represented cassette exon skipping, “poison” exon inclusion, and intron retention, phenocopying well-documented loss-of-function mutations. In contrast, relapse-associated AS of NT5C2 mRNA yielded an isoform with the functionally uncharacterized in-frame exon 6a. 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 resistance. Consistent with this finding, NT5C2ex6a and the R238W hotspot variant conferred comparable levels of resistance to 6-mercaptopurine in B-ALL cells both in vitro and in vivo. Furthermore, both NT5C2ex6a and the R238W variant induced collateral sensitivity to the inosine monophosphate dehydrogenase inhibitor mizoribine. These results ascribe to splicing perturbations an important role in chemotherapy resistance in relapsed B-ALL and suggest that inosine monophosphate dehydrogenase inhibitors, including the commonly used immunosuppressive agent mycophenolate mofetil, could be a valuable therapeutic option for treating thiopurine-resistant leukemias.Significance: Alternative splicing is a potent mechanism of acquired drug resistance in relapsed/refractory acute lymphoblastic leukemias that has diagnostic and therapeutic implications for patients who lack mutations in known chemoresistance genes.

01 Jun 2024·Transplantation Proceedings

Safety and Efficacy of Mycophenolate Mofetil Associated With Tacrolimus for Kidney-pancreas and Kidney Transplantation: A Systematic Review and Meta-Analysis of Randomized Studies

Review

Author: Datrino, Letícia Nogueira ; Tustumi, Francisco ; Riva, Wagner José ; Castilho, Pedro Henrique Baptistella Teno ; Boccuzzi, Matheus Lopes ; Silva, Rafael Matosinho ; Rocha, Jéssica Silva

INTRODUCTIONThis study evaluated the efficacy and safety of mycophenolate mofetil (MMF) associated with tacrolimus (TAC) in patients undergoing kidney-pancreas and kidney transplants, in comparison with cyclosporine (CyA), azathioprine (AZA), everolimus (EVL), sirolimus (SRL), manitimus (MAN), mizoribine (MZR), and enteric-coated mycophenolate sodium (ECMPS) in combination or monotherapy.METHODSA systematic review and meta-analysis of randomized clinical trials was performed. The outcomes comprised acute rejection, graft loss, and adverse events.RESULTSThirty studies were included. The main adverse events related to the TAC+MMF scheme were infection (36%; 95%CI: 26%-46%), including cytomegalovirus (CMV) (14%; 95%CI: 8%-20%); anemia (20%; 95%CI: 2%-37%); leukopenia (18%; 95%CI: 3%-33%); nausea (20%; 95%CI: 1%-39%); and diarrhea (26%; 95%CI:13%-40%). TAC+MMF was compared to the schemes AZA+TAC, CyA+AZA, CyA+MMF, CyA+SRL, ECMPS, EVL, MAN+TAC, MMF+SRL, MZR, TAC+AZA, TAC+EVR, TAC+MZR, TAC +SRL and TAC. TAC+MMF was associated with a lower risk of rejection than MMF monotherapy (RD: -0.24; 95%CI -0.46; -0.02). Comparing TAC+MMF with the other regimens, no significant difference was found for graft loss. TAC+MMF was associated with a higher risk of infections than MZR (RD: 0.174; 95%CI: 0.25; 0.323) and TAC monotherapy (RD: 0.07; 95%CI 0.003; 0.138).CONCLUSIONGastrointestinal 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.

01 May 2024·Current Topics in Medicinal Chemistry

Approaches Towards Better Immunosuppressive Agents

Review

Author: Walczak, Juliusz ; Iwaszkiewicz-Grześ, Dorota ; Cholewiński, Grzegorz

Abstract:Several classes of compounds are applied in clinics due to their immunosuppressive properties in transplantology and the treatment of autoimmune diseases. Derivatives of mycophe-nolic acid, corticosteroids and chemotherapeutics bearing heterocyclic moieties like methotrexate, azathioprine, mizoribine, and ruxolitinib are active substances with investigated mechanisms of action. However, improved synthetic approaches of known drugs and novel derivatives are still being reported to attempt better accessibility and therapeutic properties. In this review article, we present the synthesis of the designed chemical structures based on recent literature reports con-cerning novel compounds as promising immunosuppressive drugs. Moreover, some of the dis-cussed derivers revealed also other types of activities with prospective medicinal potential.

100 Deals associated with Mizoribine

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External Link

KEGG	Wiki	ATC	Drug Bank
D01392	Mizoribine	L04AX	DB12617

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Nephrotic Syndrome	JP	Asahi Kasei Corp.	29 Sep 1995
Rheumatoid Arthritis	JP	Asahi Kasei Corp.	02 Oct 1992
Lupus Nephritis	JP	Asahi Kasei Corp.	28 Sep 1990
Renal transplant rejection	JP	Asahi Kasei Corp.	15 Feb 1984

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Lupus Nephritis	NDA/BLA	CN	Asahi Kasei Corp.	30 Jan 2022
Nephrotic Syndrome	NDA/BLA	CN	Asahi Kasei Corp.	30 Jan 2022

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02373202 (CTgov)	Phase 3	Rheumatoid Arthritis	91	Sarilumab+Mizoribine+Tacrolimus+Sulfasalazine+Leflunomide+Bucillamine (Sarilumab 150 mg q2w + DMARDs)	axvbzoaxil(qckjkikeji) = teargtzxdu gnqxzoijoh (kizybrtxmt, xweqnuokis - mplmhdshnj) View more	-	30 Jan 2018
				Sarilumab+Mizoribine+Tacrolimus+Sulfasalazine+Leflunomide+Bucillamine (Sarilumab 200 mg q2w + DMARDs)	axvbzoaxil(qckjkikeji) = wwsbeinjik gnqxzoijoh (kizybrtxmt, kxloigqfvi - moxlhcgweu) View more
EULAR2016	Not Applicable	Polymyalgia Rheumatica	24	Mizoribine	wdbgdageuc(vvkhoitbmw) = 1 patient developed gastrointestinal symptom in MTX group, and 1 patient developed gastrointestinal symptom in MZR group zadnxxmwhd (hjfewzkftw ) View more	Positive	08 Jun 2016
				Methotrexate
ASN2015	Not Applicable	Idiopathic Membranous Glomerulonephritis \| Nephrotic Syndrome	22	Mizoribine	(hggnvfxcql) = observed in 4 patients eoftddpcwm (crxkwhgnck )	Positive	03 Nov 2015
				Prednisone
MILE 2010 (EULAR2015)	Not Applicable	Lupus Nephritis	576	Mizoribine	(hjeqpxcwof) = Adverse reactions occurred in 60 of the 443 subjects (13.5%). The main adverse reactions were 12 events (2.7%) of herpes zoster, 5 events (1.1%) of hyperuricemia, and 4 events (0.9%) of anemia. Serious adverse drug reactions were observed in 12 patients (2.7%) xcllhwqavd (hwzqkycdwt )	Positive	10 Jun 2015
EULAR2010	Not Applicable	Collagen Diseases \| Rheumatoid Arthritis	-	Mizoribine 100-150 mg/day	ywhspzbxne(dvqxtjmpfj) = no severe side effects developed ledmjmuhxp (dunfxncbaq ) View more	Positive	16 Jun 2010
EULAR2008	Not Applicable	Sjogren's Syndrome	29	Mizoribine 150 mg/day	(rbkbcuelkb) = erdjzmtdrh qyaiodwril (lcvpjemjqw, 57.0)	Positive	11 Jun 2008