Preferred Label : Amezalpat;
NCIt synonyms : PPARA Antagonist TPST-1120; PPARalpha Antagonist TPST-1120; Peroxisome Proliferator Activated Receptor Alpha Antagonist TPST-1120; PPAR Alpha Antagonist TPST-1120;
NCIt definition : An orally bioavailable, small molecule, selective and competitive antagonist of peroxisome
proliferator activated receptor alpha (PPARa), with potential immunomodulating and
antineoplastic activities. Upon oral administration, amezalpat targets, binds to and
blocks the activity of PPARa, thereby blocking transcription of PPARa target genes
leading to an intracellular metabolism shift from fatty acid oxidation (FAO) to glycolysis
in FAO-dependent tumors and reducing the production of fatty acids in the tumor microenvironment
(TME). As fatty acids are essential for tumor cell growth in FAO-dependent tumor cells
and are needed for the metabolism of suppressive immune cells in the TME, including
regulatory T-cells (Tregs), reducing the amount of fatty acids leads to a direct killing
of FAO-dependent tumor cells. It also skews macrophages from the immune suppressive
M2 phenotype to an effector M1 phenotype and facilitates the cytotoxicity of immune
effector cells, thereby stimulating an anti-tumor immune response and further killing
tumor cells. Amezalpat also restores the natural inhibitor of angiogenesis thrombospondin-1
(TSP-1) and stimulator of interferon genes (STING) in the TME. PPARa, a ligand-activated
nuclear transcription factor and metabolic checkpoint, regulates the expression of
FAO genes and lipid metabolism. It plays a key role in immunosuppression in the TME.
FAO is a metabolic pathway essential to tumor growth, survival and immunosuppression.;
UNII : 1EQ4LQN9N3;
CAS number : 1616372-41-8;
Molecule name : TPST 1120; TPST-1120;
NCI Metathesaurus CUI : CL1382244;
Origin ID : C169105;
UMLS CUI : C5417797;
Semantic type(s)
- concept_is_in_subset
- has_target
