Discovery of the 3-amino-1, 2, 4-triazine-based library as selective PDK1 inhibitors with therapeutic potential in highly aggressive pancreatic ductal adenocarcinoma
D Carbone, M De Franco, C Pecoraro… - International Journal of …, 2023 - mdpi.com
Pyruvate dehydrogenase kinases (PDKs) are serine/threonine kinases, that are directly
involved in altered cancer cell metabolism, resulting in cancer aggressiveness and …
involved in altered cancer cell metabolism, resulting in cancer aggressiveness and …
1, 2, 4-Amino-triazine derivatives as pyruvate dehydrogenase kinase inhibitors: Synthesis and pharmacological evaluation
C Pecoraro, M De Franco, D Carbone… - European Journal of …, 2023 - Elsevier
Among the different hallmarks of cancer, deregulation of cellular metabolism turned out to be
an essential mechanism in promoting cancer resistance and progression. The pyruvate …
an essential mechanism in promoting cancer resistance and progression. The pyruvate …
Structural manipulations of marine natural products inspire a new library of 3-amino-1, 2, 4-triazine PDK inhibitors endowed with antitumor activity in pancreatic ductal …
D Carbone, M De Franco, C Pecoraro, D Bassani… - Marine Drugs, 2023 - mdpi.com
Pancreatic ductal adenocarcinoma (PDAC) is one of the main aggressive types of cancer,
characterized by late prognosis and drug resistance. Among the main factors sustaining …
characterized by late prognosis and drug resistance. Among the main factors sustaining …
Unexpected discovery of dichloroacetate derived adenosine triphosphate competitors targeting pyruvate dehydrogenase kinase to inhibit cancer proliferation
Pyruvate dehydrogenase kinases (PDKs) have recently emerged as an attractive target for
cancer therapy. Herein, we prepared a series of compounds derived from dichloroacetate …
cancer therapy. Herein, we prepared a series of compounds derived from dichloroacetate …
Rational design of mitochondria-targeted pyruvate dehydrogenase kinase 1 inhibitors with improved selectivity and antiproliferative activity
Herein, triphenylphosphonium cation moieties were incorporated into a
dichloroacetophenone derivative, leading to the discovery of novel mitochondria-targeted …
dichloroacetophenone derivative, leading to the discovery of novel mitochondria-targeted …
Identification of novel piperazine-tethered phthalazines as selective CDK1 inhibitors endowed with in vitro anticancer activity toward the pancreatic cancer
Pharmacologic inhibition of the oncogenic protein kinases using small molecules is a
promising strategy to combat several human malignancies. CDK1 is an example of such a …
promising strategy to combat several human malignancies. CDK1 is an example of such a …
Development of the first generation of disulfide-based subtype-selective and potent covalent pyruvate dehydrogenase kinase 1 (PDK1) inhibitors
Y Liu, Z Xie, D Zhao, J Zhu, F Mao, S Tang… - Journal of medicinal …, 2017 - ACS Publications
Pyruvate dehydrogenase kinases (PDKs) are overexpressed in most cancer cells and are
responsible for aberrant glucose metabolism. We previously described bis (4-morpholinyl …
responsible for aberrant glucose metabolism. We previously described bis (4-morpholinyl …
Targeting pyruvate dehydrogenase kinase signaling in the development of effective cancer therapy
Pyruvate is irreversibly decarboxylated to acetyl coenzyme A by mitochondrial pyruvate
dehydrogenase complex (PDC). Decarboxylation of pyruvate is considered a crucial step in …
dehydrogenase complex (PDC). Decarboxylation of pyruvate is considered a crucial step in …
Development of pyruvate dehydrogenase kinase inhibitors in medicinal chemistry with particular emphasis as anticancer agents
Highlights•An overview of the structural information of PDKs.•The development of PDK
inhibitors as anticancer agents is described.•New thoughts in the quest for the designs of …
inhibitors as anticancer agents is described.•New thoughts in the quest for the designs of …
Targeting the pyruvate dehydrogenase complex/pyruvate dehydrogenase kinase (PDC/PDK) axis to discover potent PDK inhibitors through structure-based virtual …
L Gan, Y Yang, Z Liang, M Zhang, Y He… - European Journal of …, 2024 - Elsevier
Proliferating cancer cells are characterized by the Warburg effect, a metabolic alteration in
which ATP is generated from cytoplasmic glycolysis instead of oxidative phosphorylation …
which ATP is generated from cytoplasmic glycolysis instead of oxidative phosphorylation …