Definition
ChEBI: 2-amino-8-ethyl-4-methyl-6-(1H-pyrazol-5-yl)-7-pyrido[2,3-d]pyrimidinone is a pyrazolopyridine.
Biological Activity
Voxtalisib (SAR245409, XL765) is a dual mTOR/PI3K inhibitor with the strongest effect on p110γ with IC50 of 9 nM; also inhibits DNA-PK and mTOR. Phase 1/2.
in vitro
Voxtalisib (XL765) is the first oral dual inhibitor of PI3K and mTOR with IC50 of 39, 113, 9, 43, and ~150 nM for p110α, β, γ, δ, and mTOR, respectively. In vitro, XL765 decreased cell viability in a concentration-dependent manner.
in vivo
Oral feeding of XL765 resulted in a 12-fold increase in the number of mid-stage tumor declines compared to the control group. XL765 showed activity either alone or in combination with other drugs in various GBM xenografts. XL765 induces downregulation of PI3K downstream phosphorylated proteins: pAkt and pPRAS40, and mTOR downstream phosphorylated proteins: pS6 and p4EBP1 in cultured human xenograft tumors in vitro.
