Last update 01 Nov 2024

MDH1

Last update 01 Nov 2024

Basic Info

Synonyms

Cytosolic malate dehydrogenase, Diiodophenylpyruvate reductase, malate dehydrogenase 1

+ [3]

Introduction

Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH (PubMed:2449162, PubMed:3052244). Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation (PubMed:31538237).

Drugs associated with MDH1

FM-701

Target

MDH1 x MDH2

Mechanism

MDH1 inhibitors [+1]

Active Org.

Future Medicine Co., Ltd.

Originator Org.

Future Medicine Co., Ltd.

Active Indication

Non-Small Cell Lung Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MDH1

100 Translational Medicine associated with MDH1

0 Patents (Medical) associated with MDH1

557

Literatures (Medical) associated with MDH1

01 Jan 2025·Journal of Affective Disorders

Identifying clinical and proteomic markers for early diagnosis and prognosis prediction of major psychiatric disorders

Article

Author: Kim, Minah ; Kim, Jayoun ; Park, Dong Yeon ; Rhee, Sang Jin ; Baik, Myungjae ; Jung, Hee Yeon ; Ha, Kyooseob ; Lee, Junhee ; Roh, Sungwon ; Lee, Hyunju ; Ahn, Yong Min ; Lee, Yunna ; Han, Dohyun ; Kim, Eun Young ; Lee, Tae Young ; Kim, Hyeyoon ; Kwon, Jun Soo ; Kim, Se Hyun

BACKGROUNDTo clarify if blood proteins can predict disease progression among individuals at clinical high-risk of severe mental illness (CHR-SMI), we developed a statistical model incorporating clinical and blood protein markers to distinguish the transition group (who developed severe mental illness) (CHR-SMI-T) and from non-transition group (CHR-SMI-NT) at baseline.METHODSNinety individuals (74 at CHR-SMI: 16 patients) were monitored for ≤4 years and were the focus of predictive models. Three predictive models (1 [100 clinical variables], 2 [158 peptides], and 3 [100 clinical variables +158 peptides]) were evaluated using area under the receiver operating characteristic (AUROC) values. Clinical and protein feature patterns were evaluated by linear mixed-effect analysis within the model at 12 and 24 months among patients who did (CHR-SMI-T) and did not transition (CHR-SMI-NT) and the entire group.RESULTEighteen CHR-SMI individuals with major psychiatric disorders (first episode psychosis: 2; bipolar II disorder: 13; major depressive disorder; 3) developed disorders over an average of 17.7 months. The combined model showed the highest discriminatory performance (AUROC = 0.73). Cytosolic malate dehydrogenase and transgelin-2 levels were lower in the CHR-SMI-T than the CHR-SMI-NT group. Complement component C9, inter-alpha-trypsin inhibitor heavy chain H4, von Willebrand factor, and C-reactive protein were lower in the patient than the CHR-SMI-NT group. These differences were non-significant after FDR adjustment.LIMITATIONSSmall sample, no control for medication use.CONCLUSIONThis exploratory study identified clinical and proteomic markers that might predict severe mental illness early onset, which could aid in early detection and intervention. Future studies with larger samples and controlled variables are needed to validate these findings.

01 Dec 2024·International Immunopharmacology

IDH1/MDH1 deacetylation promotes NETosis by regulating OPA1 and autophagy

Article

Author: Shi, Chunxia ; Zhang, Xiaoya ; Gong, Zuojiong ; Wang, Yukun ; Guo, Jin ; Zhang, Danmei

BACKGROUNDAs a heterogeneous and life-threatening disease, the pathogenesis of acute liver failure (ALF) is complex. Our previous study has shown that IDH1/MDH1 deacetylation promotes ALF by regulating NETosis (a novel mode of cell death). In this article, we explore the manners of IDH1/MDH1 deacetylation regulates NETosis.METHODSIn vitro experiments, the formation of NETs was detected by immunofluorescence staining and Western blotting. LC3 fluorescence staining was used to detect autophagosome formation. To observe mitochondrial morphology, cells were stained by Mito-Tracker Red. Western blotting was used to detect the levels of autophagy protein and mitochondrial dynamin. In vivo experiments, the ALF model in mouse was established with LPS/D-gal, and the formation of NETs was detected by immunofluorescence staining and Western blotting. The autophagy levels were detected by Western blotting in liver samples.RESULTSIn dHL-60 cells, Western blotting results showed that the expression of OPA1 was higher in the IDH1/MDH1 deacetylated group compared with the IDH1/MDH1 WT group. And histone deacetylase inhibitor 6 (HDAC6i, ACY1215) decreased the expression level of OPA1 in IDH1/MDH1 deacetylated group. IDH1/MDH1 deacetylation increased the expression levels of both LC3B-II and Beclin 1, while decreasing the expression level of P62. It was reversed by ACY1215. Combined with our previous experiments, IDH1/MDH1 deacetylation upregulated autophagy concomitant with the increased expression of the markers of NETs formation. In a mouse model of ALF, ACY1215 further decreased the expression levels of LC3B-II and Beclin 1, while increasing the expression level of P62 in IDH1/MDH1 deacetylated mice.CONCLUSIONSIDH1/MDH1 deacetylation promoted NETosis by regulating autophagy and OPA1 in vitro. The regulation of neutrophil autophagy on NETosis during IDH1/MDH1 deacetylation might be masked in mice. ACY1215 might attenuate NETosis by regulating neutrophil autophagy, which alleviated ALF aggravated by IDH1/MDH1 deacetylation.

01 Dec 2024·Genes & Nutrition

Visnagin alleviates rheumatoid arthritis via its potential inhibitory impact on malate dehydrogenase enzyme: in silico, in vitro, and in vivo studies

Article

Author: Mohamed, Tarek M ; Khamis, Abeer A ; Abdelrasoul, Elsayed A ; Sharshar, Amira H ; Salem, Maha M

AbstractRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. The present study aimed to evaluate the in silico, in vitro, and in vivo inhibitory effect of visnagin on malate dehydrogenase activity and elucidate its inflammatory efficacy when combined with methotrexate in the RA rat model. The molecular docking, ADMET simulations, MDH activity, expression, and X-ray imaging were detected. Moreover, CRP, RF, (anti-CCP) antibody, (TNF-α), (IL-6), (IL-17), and (IL-10) were evaluated. The expression levels of MMP3 and FOXP3 genes and CD4, CD25, and CD127 protein levels were assessed. Histological assessment of ankle joints was evaluated. The results revealed that visnagin showed reversible competitive inhibition on MDH with inhibitory constant (Ki) equal to 141 mM with theoretical IC50 equal to 1202.7 mM, LD50 equal to 155.39 mg/kg, and LD25 equal to 77.69 mg/kg. In vivo studies indicated that visnagin exhibited anti-inflammatory effects through decreasing MDH1 activity and expression and induced proliferation of anti-inflammatory CD4+CD25+FOXP3 regulatory T cells with increasing the anti-inflammatory cytokine IL-10 levels. Moreover, visnagin reduced the levels of inflammatory cytokines and the immuno-markers. Our findings elucidate that visnagin exhibits an anti-inflammatory impact against RA through its ability to inhibit the MDH1 enzyme, improve methotrexate efficacy, and reduce oxidative stress. Graphical Abstract

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MDH1

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