Preferred Label : DNA-PK/PI3K-delta Inhibitor BR101801;
NCIt definition : An orally bioavailable inhibitor of phosphoinositide 3-kinase delta (PI3-kinase subunit
delta; PI3K-delta; PI3Kdelta) and DNA-dependent protein kinase (DNA-PK), with potential
antineoplastic and immunomodulating activities. Upon oral administration, the DNA-PK/PI3K-delta
inhibitor BR101801 inhibits the activity of both PI3K-delta and DNA-PK. This prevents
PI3K-mediated signaling pathways and may lead to the inhibition of cancer cell growth
in PI3K-overexpressing tumor cells. Specifically, since PI3K regulates c-myc expression,
inhibition of PI3K signaling may lead to a decrease in proliferation of c-myc-expressing
tumor cells. Also, by inhibiting the activity of DNA-PK, this agent interferes with
the non-homologous end joining (NHEJ) process and prevents the repair of DNA double
strand breaks (DSBs) caused by ionizing radiation or chemotherapeutic treatment. This
increases chemo- and radiotherapy cytotoxicity by inhibiting the ability of tumor
cells to repair damaged DNA. The PI3K pathway is upregulated in a variety of tumors
and plays an important role in regulating cancer cell proliferation, growth, and survival.
DNA-PK is activated upon DNA damage and plays a key role in repairing double-stranded
DNA breaks. The enhanced ability of tumor cells to repair DSBs plays a major role
in the resistance of tumor cells to chemo- and radiotherapy. In addition, BR101801
is able to decrease Tregs and increase CD8 lymphocytes.;
Molecule name : BR 101801; BR-101801;
NCI Metathesaurus CUI : CL1406238;
Origin ID : C172111;
UMLS CUI : C5417896;
Semantic type(s)
- concept_is_in_subset
