Preferred Label : 3-bromopyruvate-based Agent KAT-201;
NCIt synonyms : 3-BP-based Agent KAT-201;
NCIt definition : An intratumoral (IT) formulation of a derivative of 3-bromopyruvate (3-BP), with potential
antineoplastic activity. Upon IT administration of 3-BP-based agent KAT-201, 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-201
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-201 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-201
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 201; KAT-201;
NCI Metathesaurus CUI : CL1913090;
Origin ID : C193479;
UMLS CUI : C5785785;
Semantic type(s)
- concept_is_in_subset
