Preferred Label : 3-bromopyruvate-based Agent KAT-101;
NCIt synonyms : 3-BP-based Agent KAT-101;
NCIt definition : An orally bioavailable formulation of a derivative of 3-bromopyruvate (3-BP), with
potential antineoplastic activity. Upon oral administration of 3-BP-based agent KAT-101,
the 3-BP derivative, being structurally similar to lactic acid, specifically binds
to and enters cancer cells through monocarboxylic acid transporters (MCTs), which
are transporters for lactic acid and are overexpressed on cancer cells. Inside the
cancer cells, KAT-101 interferes with both glycolysis and mitochondrial oxidative
phosphorylation (OxPhos), thereby depleting adenosine triphosphate (ATP) levels and
thus limits energy supply needed by cancer cells to proliferate. This induces cancer
cell apoptosis and prevents cancer cell proliferation. In addition, KAT-101 is able
to release mitochondrial-bound hexokinase (HK) II (HK2) from the mitochondria, thereby
allowing mitochondrial voltage-dependent anion channels (VDACs) to bind to pro-apoptotic
proteins and increases the formation of mitochondrial permeability transition pores
(MPTPs), which induces apoptosis. KAT-101 also inhibits a variety of enzymes, including
lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH) and pyruvate dehydrogenase
kinase (PDHK). This further prevents cancer cells' metabolism. HK2 is overexpressed
in cancer cells and plays a major role in glycolysis and preventing tumor cell apoptosis.
It is bound to VDAC in cancer cells and prevents VDAC's interaction with pro-apoptotic
proteins which prevents apoptosis.;
Molecule name : KAT 101; KAT-101;
NCI Metathesaurus CUI : CL1913079;
Origin ID : C193480;
UMLS CUI : C5785786;
Semantic type(s)
- concept_is_in_subset
