Preferred Label : ATM Kinase/DNA-PK Inhibitor XRD-0394;
NCIt synonyms : Ataxia Telangiectasia Mutated Kinase/DNA-dependent Protein Kinase Inhibitor XRD-0394;
NCIt definition : An orally bioavailable, small molecule, dual inhibitor of ataxia telangiectasia mutated
kinase (ATM) and DNA-dependent protein kinase (DNA-PK), with potential radio-sensitizing
and antineoplastic activities. Upon oral administration, ATM kinase/DNA-PK inhibitor
XRD-0394 selectively targets, binds to and inhibits the activity of ATM and DNA-PK.
This inhibits ATM-mediated signaling, which may prevent DNA damage checkpoint activation,
disrupt DNA damage repair and induce tumor cell apoptosis. By disrupting DNA damage
repair, this agent may sensitize tumor cells to radiotherapy and increase its anti-tumor
activity. In addition, by inhibiting the activity of DNA-PK, this agent interferes
with the non-homologous end joining (NHEJ) process which may prevent the repair of
DNA double strand breaks (DSBs) caused by ionizing radiation. This may also increase
radiotherapy cytotoxicity leading to enhanced tumor cell death. ATM, a serine/threonine
protein kinase upregulated in a variety of cancer cell types, is activated in response
to DNA damage and plays a key role in DNA-strand repair. DNA-PK plays a key role in
the NHEJ pathway and DSB repair. The enhanced ability of tumor cells to repair DNA
damage plays a major role in the resistance of tumor cells to radiotherapy.;
Molecule name : XRD-0394; XRD 0394;
NCI Metathesaurus CUI : CL1664820;
Origin ID : C182011;
UMLS CUI : C5557419;
Semantic type(s)
- concept_is_in_subset
- has_target
