Last update 01 Nov 2024

MCT4

Last update 01 Nov 2024

Basic Info

Synonyms

MCT 4, MCT3, MCT4

+ [6]

Introduction

Proton-dependent transporter of monocarboxylates such as L-lactate and pyruvate (PubMed:11101640, PubMed:23935841, PubMed:31719150). Plays a predominant role in L-lactate efflux from highly glycolytic cells (By similarity).

Drugs associated with MCT4

NGT-008

Target

MCT1 x MCT4

Mechanism

MCT1 inhibitors [+1]

Active Org.

Nirogyone Therapeutics, LLC

Originator Org.

Nirogyone Therapeutics, LLC

Active Indication

Breast Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

VB-253

Target

MCT4

Mechanism

MCT4 inhibitors

Active Org.

Harvard Medical School

Originator Org.

Harvard Medical School

Active Indication

Pulmonary Fibrosis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

18F-FACH (Helmholtz-Zentrum Dresden-Rossendorf)

Target

MCT1 x MCT4

Mechanism

MCT1 inhibitors [+1]

Active Org.

Helmholtz-Zentrum Dresden-Rossendorf e. V.

Originator Org.

Helmholtz-Zentrum Dresden-Rossendorf e. V.

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MCT4

100 Translational Medicine associated with MCT4

0 Patents (Medical) associated with MCT4

956

Literatures (Medical) associated with MCT4

01 Jan 2025·Journal of Ethnopharmacology

Comparison of chemical composition between imitation wild and transplanted Astragali Radix and their therapeutic effects on heart failure

Article

Author: Wang, Min ; Sun, Xiaobo ; Chen, Rongchang ; Zhu, Yindi ; Zhang, Chongyang

ETHNOPHARMACOLOGICAL RELEVANCEAstragali Radix (AR) is a traditional Chinese herbal medicine, which has been widely used on treating chronic heart failure (CHF) in clinical practice. Two main types of AR in the market are the imitation wild AR (5YAR) and transplanted AR (2YAR). It remains unclear whether there are variations in the anti-heart failure effects of AR with different growth years. Further research is required to explore the material composition and mechanisms of AR in combating heart failure.AIM OF THE STUDYThe aim of the study was to compare the main chemical composition content and the protective effects of 2YAR and 5YAR on heart failure.MATERIALS AND METHODSEthanol extracts of 2YAR and 5YAR were prepared, and chemical composition analysis was conducted. C57BL/6 mice were subcutaneously injected with ISO to induce heart failure (HF) and were administrated with a corresponding dose of the extracts of 2YAR and 5YAR by gavage for 28 days. Cardiac function was evaluated using echocardiography. The serum levels of enzymes related to myocardial injury, oxidative stress, and inflammation were detected. The left ventricle was excised for hematoxylin-eosin, Masson, Sirius Red, wheat germ agglutinin, and TUNEL staining. Electron microscopy examination of mitochondrial structure in myocardial cells. Protein expression of monocarboxylate transporter 4 (MCT4), Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated serine/threonine protein kinase (p-AKT), and phosphorylated insulin receptor substrates 1 (p-IRS-1) were detected by immunohistochemistry and Western blot.RESULTSThe content of saponins and flavonoids in 5YAR was higher than that in the 2YAR. However, the content of polysaccharides in 5YAR is lower than in 2YAR. The treatment of 2YAR and 5YAR daily for 28 days prevented ISO-induced myocardial damage, including the decrease in serum cardiac enzymes and cardiomyocyte apoptotic index, and improvement in heart function and mitochondrial structure. Additionally, 2YAR and 5YAR reduced serum inflammatory factors and myocardial fibrosis levels. Treatment with 2YAR and 5YAR also decreased MCT4 expression and enhanced PGC-1α, p-AKT, p-AMPK, and p-IRS-1 expression in heart tissues.CONCLUSIONSThe 5YAR was better than 2YAR in anti-heart failure, which may be related to the increase in saponins and flavonoids content. AR exerts anti-heart failure effect by improving mitochondrial function and ameliorating cardiac insulin resistance through activation of the AMPK/PGC1α and IRS/AKT pathways.

01 Dec 2024·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

ETS1 drives EGF-induced glycolytic shift and metastasis of epithelial ovarian cancer cells

Article

Author: Roy, Sib Sankar ; Chatterjee, Priti ; Chowdhury, Shreya Roy ; Ghosh, Deepshikha

Epithelial ovarian cancer (EOC), a leading cause of gynecological cancer-related morbidity and mortality and the most common type of ovarian cancer (OC), is widely characterized by alterations in the Epidermal Growth Factor (EGF) signaling pathways. The phenomenon of metastasis is largely held accountable for the majority of EOC-associated deaths. Existing literature reports substantiate evidence on the indispensable role of metabolic reprogramming, particularly the phenomenon of the 'Warburg effect' or aerobic glycolysis in priming the cancer cells towards Epithelial to Mesenchymal transition (EMT), subsequently facilitating EMT. Considering the diverse roles of growth factor signaling across different stages of oncogenesis, our prime emphasis was laid on unraveling mechanistic details of EGF-induced 'Warburg effect' and resultant metastasis in EOC cells. Our study puts forth Ets1, an established oncoprotein and key player in OC progression, as the prime metabolic sensor to EGF-induced cues from the tumor microenvironment (TME). EGF treatment has been found to induce Ets1 expression in OC cells predominantly through the Extracellular Signal-Regulated Kinase1/2 (ERK1/2) pathway activation. This subsequently results in pronounced glycolysis, characterized by an enhanced lactate production through transcriptional up-regulation of key determinant genes of the central carbon metabolism namely, hexokinase 2 (HK2) and monocarboxylate transporter 4 (MCT4). Furthermore, this study reports an unforeseen combinatorial blockage of HK2 and MCT4 as an effective approach to mitigate cellular metastasis in OC. Collectively, our work proposes a novel mechanistic insight into EGF-induced glycolytic bias in OC cells and also sheds light on an effective therapeutic intervention approach exploiting these insights.

01 Nov 2024·Biochemical and Biophysical Research Communications

Knockdown of SLC16A3 decreases extracellular lactate concentration in hepatocellular carcinoma, alleviates hypoxia and induces ferroptosis

Article

Author: Yang, Dashuai ; Zhao, Kailiang ; Wu, Zhongkai ; Shen, Jie ; Wang, Xin ; Yu, Bin ; Zhou, Yu ; Ding, Youming

SLC16A3/monocarboxylate transporter 4 (MCT4) regulates intracellular lactate transport and is highly expressed in many tumors, indicating poor prognosis. It may be related to inducing hypoxia, apoptosis and other mechanisms, but the study of MCT4 in HCC is far from complete. In this study, we first analyzed the expression of SLC16A3 in HCC tumor and non-tumor tissue samples based on TCGA data and immunohistochemistry. Subsequently, the effects of SLC16A3 expression on cell proliferation and invasion were analyzed using hepatocellular carcinoma (HCC) lines, and Western blot (WB) analysis was performed to explore the changes in pathway proteins and ferroptosis proteins. Finally, the drug sensitivity was tested by CCK8 kit. We found that SLC16A3 was significantly upregulated in tumor tissues, and was significantly correlated with TNM stage, histological grade, and macrovascular invasion. TCGA data and WB analysis showed that the high expression of SLC16A3 induced hypoxia, and knockdown could reverse hypoxia and inhibit ERK phosphorylation, thus limiting the malignant behavior of HCC cells. Moreover, knockdown of SLC16A3 significantly increased the level of lipid peroxidation and reactive oxygen species (ROS), while the expressions of GPX4, DHODH and SLC7A11 were inhibited. The expression of SLC16A3 affected the sensitivity of HCC cells to chemotherapy and targeted drugs, and RNA sequencing data suggested that the expression level influenced tumor microenvironment and response to immunotherapy. So, we draw a conclude that SLC16A3 is associated with poor prognosis of HCC. Inhibition of SLC16A3 expression is a potential therapeutic target for HCC.

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MCT4

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