Preferred Label : Adenosine A2B Receptor Antagonist PBF-1129;
NCIt synonyms : A2BR Antagonist PBF-1129;
NCIt definition : An orally bioavailable antagonist of the immunomodulatory checkpoint molecule adenosine
A2B receptor (A2BR; ADORA2B), with potential anti-inflammatory, immunomodulating and
antineoplastic activities. Upon administration, A2BR antagonist PBF-1129 competes
with adenosine for binding to A2BR expressed on various cancer cell types and numerous
immune cells, such as dendritic cells (DCs), mast cells, macrophages and lymphocytes.
This inhibits A2BR activity and prevents adenosine/A2BR-mediated signaling. The inhibition
of A2BR in cancer cells prevents activation of downstream oncogenic pathways, which
leads to an inhibition of cell proliferation and metastasis. A2BR inhibition also
prevents the release of various growth factors, cytokines and chemokines, such as
vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) and angiopoietin-2
(Ang2) from immune cells, which may abrogate the adenosine-mediated immunosuppression
in the tumor microenvironment (TME) and activate the immune system to exert anti-tumor
immune responses against cancer cells leading to tumor cell killing. In addition,
under non-cancerous inflammatory conditions, inhibition of A2BR leads to reduced activation
and proliferation of various immune cells, which results in decreased pro-inflammatory
cytokine production and may prevent inflammation. A2BR, a G protein-coupled signaling
receptor, is expressed on the cell surfaces of numerous immune cells and is often
overexpressed on a variety of cancer cell types; it plays a key role in their proliferation,
progression and metastasis. Adenosine is overproduced under inflammatory conditions
and plays a key role in pro-inflammatory actions. Adenosine is often overproduced
by tumor cells and plays a key role in immunosuppression and tumor cell proliferation.
The pro- and anti-inflammatory effects of adenosine and A2BR are cell type-specific
and dependent on the extracellular microenvironment.;
Molecule name : PBF 1129; PBF-1129;
NCI Metathesaurus CUI : CL550982;
Origin ID : C148435;
UMLS CUI : C4725031;
Semantic type(s)
- concept_is_in_subset
- has_target
