Uses
AZD-8835 can be used as an inhibitor in biological cell and animal experiments.
Biological Activity
azd8835 is a dual pi3kα and pi3kδ inhibitor.the pik3ca gene, encoding the p110α catalytic unit of pi3kα, is one of the most mutated oncogenes in human cancer. therefore, pi3kα is a critical target in identifying inhibitors and testing their therapeutic application.
in vitro
azd8835 was identified as a potent dual inhibitor of pi3kα and pi3kδ with good selectivity versus pi3kβ, pi3kγ, as well as other kinases that readily inhibited cell growth with mutant pik3ca status, such as in estrogen receptor-positive breast cancer cell lines including mcf7, bt474, and t47d [1].
in vivo
previous animal study demonstrated that azd8835 had antitumor efficacy in breast cancer xenograft models when azd8835 was continuously dosed. in addition, the monotherapy of azd8835 was found to be able to induce tumor xenograft regression by using intermittent high-dose scheduling (ihds). furthermore, azd8835 ihds treatment in combination with other targeted therapeutic agents could further enhance its antitumor activity by up to 92% regression [1].
target
| Target | Value |
PI3Kδ
(Cell-based assay) | 5.7 nM |
PI3Kα
(Cell-free assay) | 6.2 nM |
< td style="border-bottom: 1px dotted #ccc;padding: 5px;"> PI3Kγ
(Cell-based assay) 90 nM |
PI3Kβ
(Cell-based assay) | 431 nM |
IC 50
6.2 and 5.7 nm for pi3kα and pi3kδ, respectively
References
[1] hudson k et al. intermittent high-dose scheduling of azd8835, a novel selective inhibitor of pi3kα and pi3kδ, demonstrates treatment strategies for pik3ca-dependent breast cancers. mol cancer ther.2016 may;15(5):877-89.
