Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0017636 (
glioblastoma
)
18,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Phosphoglycerate kinase 1
(
PGK1
) acts as both a glycolytic enzyme and a protein kinase playing critical roles in cancer progression, thereby being regarded as an attractive therapeutic target for cancer treatment. However, no effective inhibitor of
PGK1
has been reported. Here, we demonstrate that GQQ-792, a thiodiketopiperazine derivative from marine nature products, is a non-ATP-competitive inhibitor of
PGK1
with the disulfide group within the structure of GQQ-792 as a key pharmacophore. The disulfide group of GQQ-792 binds to Cys379 and Cys380 of
PGK1
, resulting in occlusion of ATP from binding to
PGK1
. GQQ-792 treatment blocks hypoxic condition- and EGF stimulation-enhanced protein kinase activity of
PGK1
that phosphorylates PDHK1 at T338 in
glioblastoma
cells; this treatment leads to decreased lactate production and glucose uptake, and subsequent apoptosis of
glioblastoma
cells. Animal studies reveal that GQQ-792 significantly inhibits the growth of tumor derived from
glioblastoma
cells. These findings underscore the potential of GQQ-792 as a promising anticancer agent and pave an avenue to further optimize the structure of GQQ-792 basing on its target molecule and pharmacophore in future.
...
PMID:Identification of a novel non-ATP-competitive protein kinase inhibitor of PGK1 from marine nature products. 3321 41
