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Last update 23 Jan 2025

PDK3

Last update 23 Jan 2025

Basic Info

Synonyms

[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial, PDHK3, PDK3

+ [4]

Introduction

Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.

Drugs associated with PDK3

INY-01-140-1

Target

PDHK1 x PDHK2 x PDK3

Mechanism

PDHK2 inhibitors [+2]

Active Org.-

Originator Org.-

Active Indication-

Inactive Indication-

Drug Highest Phase-

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PDK3

100 Translational Medicine associated with PDK3

0 Patents (Medical) associated with PDK3

152

Literatures (Medical) associated with PDK3

01 Jan 2025·European Journal of Pharmacology

Melittin suppresses aerobic glycolysis by regulating HSF1/PDK3 to increase chemosensitivity of NSCLC

Article

Author: Li, Xiaodan ; Wang, Yuhan ; Huang, Gang ; Zhou, Chuanqiang ; Liu, Jiao ; Qian, Minxuan ; Zou, Zhangyan ; Lu, Changlian ; Yuan, Jiaying ; Jin, Mingming

Non-small cell lung cancer (NSCLC), although considered non-immunogenic, is often resistant to chemotherapy agents during the course of treatment in clinical patients. Melittin (C₁₃₁H₂₂₉N₃₉O₃₁, CAS: 20449-79-0), the major component of honey bee venom, is a promising anticancer drug. However, the mechanism employed by melittin to reverse chemotherapy resistance of NSCLC cells remains unknown. In this study, the Cell Counting Kit 8, ethynyl deoxyuridine assay, and other assays were utilized to elucidate the melittin effects upon cell proliferation. Proteomics, lung cancer (LC) tissue chip, and Western blot analysis were used to identify potential targets of melittin. A549/DDP cells were employed to investigate the melittin effects against cisplatin resistance. Also, an in vivo animal experiment was conducted to further clarify the regulatory function of melittin towards cisplatin resistance of A549/DDP cells. Results showed that melittin inhibited malignant progression of A549/DDP cells by down-regulation of pyruvate dehydrogenase kinase 3 (PDK3)-mediated aerobic glycolysis and inhibition of heat shock factor 1 (HSF1) expression. The therapeutic effect of melittin was increased by combination with KNK437 and impaired chemotherapy resistance regarding A549/DDP cells via reversing aerobic glycolysis. The in vivo experiments confirmed that melittin incremented A549/DDP cell cisplatin sensitivities. Collectively, the data suggested that melittin suppressed aerobic glycolysis by regulating HSF1/PDK3, which incremented cisplatin sensitivity of A549/DDP cells. It may provide a new treatment method for chemotherapy resistance in clinical NSCLC patients.

01 Jan 2025·Molecular and Cellular Biochemistry

Lycorine hydrochloride interferes with energy metabolism to inhibit chemoresistant glioblastoma multiforme cell growth through suppressing PDK3

Article

Author: Niu, Chaoshi ; Hu, Shanshan ; Ye, Chengkun ; Mu, Maolin ; Niu, Wanxiang ; Dong, Qingsheng ; Wu, Pengfei

Glioblastoma multiforme (GBM) is the highest grade of glioma. Tumours, including GBM, possess reprogrammed metabolism, such as altered aerobic glycolysis and aberrant energy production. Lycorine hydrochloride (LH) was extracted from the bulb of Lycoris radiata. The previous study indicated that LH exerts antiviral, anti-inflammatory and antitumour effects. However, the effect of LH on GBM and the underlying molecular mechanism remain unclear. Our study revealed that LH restrained chemoresistant GBM cells growth by inhibiting PDK3 expression in vitro and in vivo. Functionally, LH inhibited the proliferation and invasive capacity of chemoresistant GBM cells in dose-dependent manner. Metabolomics and cellular energy analyses showed that LH decreased extracellular acidification rates while increased oxidative respiration and ROS levels. Mechanistically, LH inhibits the growth of GBM chemoresistant cells by regulating the expression of apoptosis-related proteins, while overexpression of of PDK3 can reverse the antitumor effect of LH. In conclusion, our study revealed that LH could reprogramme cell energy metabolism, including aerobic glycolysis suppression and oxidative phosphorylation hyperactivation by inhibiting PDK3. PDK3 may be a candidate therapeutic target for chemoresistant GBM treatment with LH.

01 Nov 2024·Reproductive Sciences

Correlation of Glycolysis-immune-related Genes in the Follicular Microenvironment of Endometriosis Patients with ART Outcomes

Article

Author: Chen, Qizhen ; Wu, Huanmei ; Liang, Jiaqi ; Li, Li ; Wang, Yanqiu ; Guo, Shana

Endometriosis (EMT) -related infertility has been a challenge for clinical research. Many studies have confirmed that abnormal alterations in the immune microenvironment and glycolysis are instrumental in causing EMT-related infertility. Recently, our research team identified several key glycolysis-immune-related genes in the endometrial cells of EMT patients. This study aimed to further investigate the expression patterns of pyruvate dehydrogenase kinase 3 (PDK3), glypican-3 (GPC3), and alcohol dehydrogenase 6 (ADH6), which are related to glycolysis and immunity, in the follicular microenvironment of infertile patients with EMT using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) assays. According to the results, compared to the patients with tubal factor infertility, the concentrations of PDK3 and GPC3 were considerably increased in the follicular environment of EMT patients, while ADH6 expression was significantly reduced. The number of oocytes retrieved, the transferable embryo rate, and the cumulative clinical pregnancy rate of EMT patients were significantly reduced, and there was a correlation with the level of PDK3, GPC3, and ADH6 in Follicular Fluid (FF). The area under the receiver operating characteristic (ROC) curve for predicting clinical pregnancy in infertile patients with EMT for PDK3, GPC3, ADH6, and their combination was 0.732, 0.705, 0.855, and 0.879, respectively (P < 0.05). In conclusion, our research indicates that glycolysis-immune-related genes may contribute to infertility in EMT patients through immune infiltration, and disruption of mitochondrial and oocyte functions. The combined detection of PDK3, GPC3, and ADH6 in FF helps to predict clinical pregnancy outcomes in infertile patients with EMT.

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