Buparlisib is an oral pan-PI3K inhibitor
that targets all four isoforms of class I
PI3K (α, β, γ, δ)
1
Buparlisib crosses the blood–brain barrier, which
could potentially have an impact on brain
metastases
2
Pan-PI3K inhibitors may be effective in tumors
with a range of molecular drivers
(i.e. signaling via multiple PI3K isoforms)
3–6
The MTD of single-agent buparlisib has been
defined as 100 mg/day in a
first-in-man Phase I clinical trial (NCT01068483)
7
Buparlisib is a Pan-Class I PI3K Inhibitor
PI3K
RTK
PIP
2
PIP
3
AKT
PTEN
mTORC1
mTORC2
Buparlisib
Pan-PI3K
CNS, central nervous system; MTD, maximum tolerated dose.
1. Maira SM, et al. Mol Cancer Ther 2012;11:317–328; 2. Nanni P, et al. PLoS One 2012;7:e39626;
3. Liu P, et al. Nat Rev Drug Discov 2009;8:627–644; 4. Kang S, et al. Proc Natl Acad Sci USA
2006;103:1289–1294;
5. Jia S, et al. Curr Opin Cell Biol 2009;21:199–208; 6. Engelman JA. Nat Rev Cancer 2009;9:550–562;
7. Rodon J, et al. Invest New Drugs 2014;32:670–681.
