XL765 (VOXTALISIB, SAR245409)

Background Information:

XL765 (Voxtalisib, SAR245409, Sanofi)*, a
PYRIDOPYRIMIDINONE-derivative, is a highly selective, potent and
reversible ATP-competitive inhibitor of pan-Class I PI3K (α, β, γ, and
δ) and mTORC1/mTORC2. It is orally active, highly selective over 130
other protein kinases. In cellular assays, XL765 inhibits the formation
of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K,
and S6 phosphorylation in multiple tumor cell lines with different
genetic alterations affecting the PI3K pathway. In mouse xenograft
models, oral administration of XL-765 results in dose-dependent
inhibition of phosphorylation of AKT, p70S6K, and S6 with a duration of
action of approximately 24 hours. Repeat dose administration of XL765
results in significant tumor growth inhibition in multiple human
xenograft models in nude mice that is associated with antiproliferative,
antiangiogenic, and proapoptotic effects (ref. 1).*

Reference:

1. P. W. Yu, et al., Characterization of the Activity of the
PI3K/mTOR Inhibitor XL765 (SAR245409) in Tumor Models with Diverse
Genetic Alterations Affecting the PI3K Pathway, Mol Cancer Ther, May
2014 13; 1078-91.
2. K. P. Papadopoulos, et al., Phase I Safety, Pharmacokinetic, and
Pharmacodynamic Study of SAR245409 (XL765), a Novel, Orally Administered
PI3K/mTOR Inhibitor in Patients with Advanced Solid Tumors, Clin Cancer
Res, May 1, 2014 20; 2445.

APIM050265: XL765 (VOXTALISIB, SAR245409)

CAS No.: 934493-76-2.
Molecular Formula: C₁₃H₁₄N₆O?0.2H₂O.
Molecular Weight: 273.9.
Purity: >99% (HPLC at 214 and 254 nm).
QC: HPLC-MS, ¹HNMR, and Quantitative Elemental Analysis.
Solubility: Soluble in DMSO.
Storage: Store at 0°C (short term), -20°C (long term), desiccated.