Target intelligence / Profile preview

Phosphofructokinase, platelet type (PFKP)

Target
PFKP
Molecular classification
Enzyme, Kinase, Glycolytic enzyme
01

Overview

Phosphofructokinase, platelet type (PFKP) is a key regulatory enzyme in glycolysis that catalyzes the irreversible conversion of fructose 6-phosphate to fructose 1,6-bisphosphate using ATP as a phosphate donor[1][4]. PFKP is the predominant isoform of phosphofructokinase-1 (PFK-1) in platelets and is expressed in various tissues, including fibroblasts and many cancers[1][3]. As the rate-limiting step in glycolysis, PFKP plays an essential role in regulating cellular energy metabolism and supporting rapid cell proliferation. In cancer cells, PFKP is frequently upregulated or stabilized—such as by AKT-dependent phosphorylation at Ser386, which promotes glycolysis, cell proliferation, migration, invasion, and metabolic reprogramming characteristic of the Warburg effect[2][3][5]. Overexpression or altered regulation of PFKP has been implicated in the progression and aggressiveness of multiple cancers and is associated with poor prognosis in glioblastoma and other malignancies[2][5]. PFKP is also implicated in rare genetic diseases involving energy metabolism. Due to its central role in cancer cell metabolism, PFKP is a potential therapeutic target, though direct clinical inhibitors are not yet available.

Other names
ATP-dependent 6-phosphofructokinase, platelet typePFKFATP-PFKPFK-PPFK-C6-phosphofructokinase type Cphosphofructo-1-kinase isozyme Cphosphohexokinasephosphofructokinase 1phosphofructokinase, plateletPFKAP
02

Mechanism of action

Inhibition of glycolysis via phosphorylation interference or direct enzymatic inhibition Suppression of metabolic reprogramming in cancer by blocking AKT-mediated PFKP stabilization and activity

03

Biological functions

Glycolysis (rate-limiting step)Regulation of cellular energy metabolismModulation of cell proliferationRegulation of apoptosisCellular metabolic reprogrammingResponse to cellular stress
04

Disease associations

Cancer (e.g., glioblastoma, non-small cell lung cancer, renal cell carcinoma, breast cancer, hepatocellular carcinoma, bladder cancer)Glycogen storage disease VIIIntellectual developmental disorder, autosomal recessive 5
05

Safety considerations

Metabolic toxicity (risk with systemic glycolysis inhibition)Possible off-target effects impacting cellular energy in normal tissuesHematologic or neurologic effects due to impact on ATP production in non-cancerous cells
06

Interacting drugs

MK-2206 (AKT inhibitor, affects PFKP phosphorylation)[2]

2 more in the full profile.

07

Biomarkers

PFKP expression (as a prognostic or predictive marker in certain cancers, e.g., glioblastoma, NSCLC)[2][5]Phosphorylation status at Ser386 (marker of AKT pathway activation and poor prognosis in glioblastoma)[2]

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