Preferred Label : Mutant-selective PI3K-alpha H1047R Inhibitor LOXO-783;
NCIt synonyms : PI3Kalpha H1047R Inhibitor LOXO-783; PI3Ka H1047R Inhibitor LOXO-783; PIK3CA H1047R Mutation Inhibitor LOX-22783; PI3Kalpha H1047R Mutant Inhibitor LOXO-783;
NCIt definition : An orally bioavailable, brain penetrative, selective irriversible inhibitor of the
class I phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha
(phosphoinositide 3-kinase alpha; PIK3CA; PI3K p110alpha) mutant H1047R, with potential
antineoplastic activity. Upon oral administration, mutant-selective PI3K-alpha H1047R
inhibitor LOXO-783 selectively targets and allosterically binds to the PIK3CA mutated
form PI3Ka H1047R, thereby preventing the activity of the H1047R mutant. This prevents
PIK3CA H1047R-mediated activation of the PI3K/Akt (protein kinase B)/mammalian target
of rapamycin (mTOR) pathway. This results in both apoptosis and growth inhibition
in PIK3CA H1047R-mutant expressing tumor cells. By specifically targeting the PIK3CA
H1047R mutation, LOXO-783 may be more efficacious and less toxic than other PI3K-alpha
inhibitors that are not mutant specific. Dysregulation of the PI3K/Akt/mTOR pathway
is often found in solid tumors and results in the promotion of tumor cell growth,
survival, and resistance to chemo- and radio-therapy. PIK3CA, one of the most frequently
mutated oncogenes, encodes the p110-alpha catalytic subunit of the class I PI3K. LOXO-783
is able to penetrate the blood-brain-barrier (BBB).;
Molecule name : LOX 22783; LOX-22783; LOXO-783; LY-3849524; LOXO 783; LY 3849524;
NCI Metathesaurus CUI : CL1792169;
Origin ID : C187335;
UMLS CUI : C5706403;
Semantic type(s)
- concept_is_in_subset
- has_target
