Preferred Label : Adenosine A2B Receptor Antagonist TT-702;
NCIt synonyms : A2BR Antagonist TT-702; A2B Receptor Antagonist TT-702;
NCIt definition : An orally bioavailable prodrug and selective antagonist of the immunomodulatory checkpoint
molecule adenosine A2B receptor (A2BR; ADORA2B), with potential anti-inflammatory,
immunomodulating and antineoplastic activities. Upon oral administration, A2BR antagonist
TT-702 is converted to its active metabolite TT-478. TT-478 selectively binds to and
blocks A2BR expressed on various cancer cell types and numerous immune cells, such
as dendritic cells (DCs), mast cells, macrophages and lymphocytes. This prevents the
binding of adenosine to A2BR, inhibits A2BR activity and prevents adenosine/A2BR-mediated
signaling. This abrogates adenosine/A2BR-mediated immunosuppression, activates immune
stimulatory cell, such as DCs and cytotoxic T-lymphocytes (CTLs), and reduces immunosuppressive
cells myeloid-derived suppressor cells (MDSCs) and regulatory T-lymphocytes (Tregs).
This suppresses cancer cell growth, which leads to an inhibition of cell proliferation
and metastasis. A2BR inhibition also prevents the release of various growth factors,
cytokines and chemokines, which may further abrogate the adenosine-mediated immunosuppression
in the tumor microenvironment (TME). This further activates the immune system to exert
anti-tumor immune responses against tumor 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, especially under hypoxic
conditions; 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 : TT 702; TT-702;
NCI Metathesaurus CUI : CL1792024;
Origin ID : C187108;
UMLS CUI : C5706355;
Semantic type(s)
- concept_is_in_subset
- has_target
