Request Demo

Last update 08 May 2025

PFKM

Last update 08 May 2025

Basic Info

Synonyms

6-phosphofructokinase type A, ATP-dependent 6-phosphofructokinase, muscle type, ATP-PFK

+ [9]

Introduction

Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.

Drugs associated with PFKM

KF-52

Target

PFKM

Mechanism

PFKM inhibitors

Active Org.

Kansai University

Originator Org.

Kansai University

Active Indication

Acidosis, Lactic [+1]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PFKM

100 Translational Medicine associated with PFKM

0 Patents (Medical) associated with PFKM

591

Literatures (Medical) associated with PFKM

01 Jul 2025·Annals of Hepatology

The promoting effect of the POU3F2/METTL16/PFKM cascade on glycolysis and tumorigenesis of hepatocellular carcinoma

Article

Author: Chen, Ming ; Peng, Zhong ; Wen, Wu ; Yang, Yuan ; Hu, Guangsheng

INTRODUCTION AND OBJECTIVESDeregulation of m⁶A methylation, the most prevailing RNA modification, participates in cancer pathogenesis. METTL16, an atypical methyltransferase, functions as a pro-tumorigenic factor in hepatocellular carcinoma (HCC). Here, we explored the action of METTL16 on HCC glycolysis and the associated mechanism.MATERIALS AND METHODSExpression analysis was done by quantitative PCR, immunoblotting, or immunohistochemistry. Cell sphere formation, invasiveness, apoptosis, proliferation and viability were detected by sphere formation, transwell, flow cytometry, EdU and CCK-8 assays, respectively. Xenograft studies were performed to analyze the role in vivo. Methylated RNA immunoprecipitation (MeRIP) and RIP assays were used to verify the METTL16/PFKM relationship. PFKM mRNA stability was tested by actinomycin D treatment. Chromatin immunoprecipitation (ChIP) and luciferase assays were performed to analyze the POU3F2/METTL16 relationship.RESULTSIn HCC, METTL16 expression was elevated, and increased levels of METTL16 transcript predicted poor HCC prognosis. METTL16 deficiency resulted in suppressed HCC cell growth, invasiveness and sphere formation. Moreover, METTL16 depletion diminished HCC cell glycolysis. Mechanistically, PFKM expression was positively associated with METTL16 expression. METTL16 mediated m6A methylation to stabilize PFKM mRNA via an IGF2BP3-dependent manner. Restored PFKM expression exerted a counteracting effect on METTL16 deficiency-mediated in vitro cell phenotype alterations and in vivo xenograft growth suppression. Furthermore, POU3F2 promoted the transcription of METTL16 in HCC cells.CONCLUSIONSOur findings define the crucial role of the POU3F2/METTL16/PFKM axis in HCC pathogenesis, offering the potential opportunity to combat HCC.

01 Jul 2025·European Journal of Pharmacology

Irisin attenuates liver fibrosis by regulating energy metabolism and HMGB1/β-catenin signaling in hepatic stellate cells

Article

Author: Wang, Xu ; Hou, Minna ; He, Qi ; Li, Jing ; Liu, Yunting ; Hou, Yali ; Li, Ying ; Bai, Ning ; Liu, Xin ; Li, Fang

Liver fibrosis is characterized by excessive extracellular matrix accumulation during chronic liver disease progression. Hepatic stellate cell (HSC) activation involves metabolic reprogramming, while both HMGB1 and β-catenin pathways have been implicated in HSC activation and liver fibrosis progression. Given irisin's established role in metabolic regulation and emerging evidence of its anti-fibrotic properties, we investigated its effects on HSC activation and liver fibrosis, focusing on potential metabolic regulation through the HMGB1/β-catenin pathway. Using both in vitro HSC-T6 cell culture and in vivo CCl₄-induced rat liver fibrosis model, we analyzed irisin's impact on HSC metabolism and fibrosis progression. Our results demonstrated that irisin dose-dependently suppressed HSC-T6 cell viability and glycolytic metabolism, significantly reducing ATP levels, glucose consumption, and lactate production at concentrations of 80-100 nmol/L. Irisin treatment markedly inhibited HSC-T6 cell proliferation and migration while inducing cellular senescence, as evidenced by increased H3K9me3, γ-H2AX, P16, and P21 expression. Mechanistically, irisin systematically downregulated key glycolytic enzymes (HK2, PFK1, PKM2, LDHA) and modulated the HMGB1/β-catenin pathway by reducing both cytoplasmic HMGB1 expression and β-catenin nuclear translocation. In the CCl₄-induced rat model, irisin treatment significantly ameliorated liver fibrosis, as evidenced by reduced collagen deposition and α-SMA expression, while improving liver function indicators and decreasing serum fibrosis markers (HA, PIIIP, HMGB1), showing therapeutic effects comparable to colchicine. These findings reveal irisin's anti-fibrotic effects through metabolic regulation and HMGB1/β-catenin pathway modulation, suggesting its potential as a therapeutic agent for liver fibrosis.

01 Jul 2025·Biochemical Pharmacology

Increased SUMO-activating enzyme subunit 1 promotes glycolysis and fibrotic phenotype of diabetic nephropathy

Article

Author: Sailike, Ali ; Haimiti, Shayila ; Wang, Yitian ; Wusiman, Reziwanguli ; Yang, Miaoyan ; Abuduaini, Hanikezi ; Gu, Meijun ; Gao, Lei

Renal fibrosis is a prominent feature of diabetic nephropathy (DN), and the connection between renal fibrosis and abnormal glycolysis is not fully understood. SUMO-activating enzyme subunit 1 (SAE1) plays a crucial role in the SUMO modification process and is related to abnormal glycolysis. Despite this, the specific role of SAE1 in DN and its mechanism are not well defined. To investigate this, a streptozotocin-induced diabetic CD1 mice model was used, with SAE1 suppression achieved through systemic administration of SAE1 siRNA. In parallel, human renal proximal tubular tubule HK2 cells transfected with siSAE1 were exposed to high glucose for in vitro studies. The study revealed that SAE1 levels were elevated in diabetic kidney, and the deletion of SAE1 mitigated renal fibrosis in DN mice. Such suppression in SAE1 was associated with the lower expression of hypoxia inducible factor-1α (HIF-1α) and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), these alterations subsequently improved abnormal glycolysis and mesenchymal transformations in vivo and in vitro. Further experiments discovered that SAE1 stabilized transcription factor HIF-1α expression through SUMOylation, promoting PFKFB3 transcription, which enhanced glycolysis characterized by increased PFK1 activity and lactate production. Additionally, pharmacological inhibition of PFKFB3 reduced renal fibrosis in DN mice, while overexpression of PFKFB3 partly restored the glycolysis and mesenchymal transformations inhibited by SAE1 knockdown in vitro. These data demonstrate that SAE1 promotes abnormal glycolysis by HIF-1α/PFKFB3 which is responsible for the fibrotic phenotype of diabetic kidney. Inhibition of SAE1 could be an alternative strategy in combating diabetes associated-kidney fibrosis via improving aberrant glycolysis.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

PFKM

Basic Info

Related

Analysis