Voxtalisib

Voxtalisib (CAS No.: 934493-76-2) is a synthetic small molecule classified as a dual inhibitor that simultaneously inhibits class I phosphoinositide 3-kinases (PI3K) and mechanistic target of rapamycin (mTOR). It is mainly used for mechanism elucidation and tool compound evaluation in biomedical research and drug discovery settings such as signal transduction and tumor biology; in vitro, it shows high potency and selectivity toward PI3K catalytic isoforms, with the strongest inhibition against p110γ (IC50 approximately 9 nM), and significant activity against p110α, p110δ, and p110β (IC50 approximately 39, 43, and 110 nM, respectively). It also directly inhibits mTORC1 and mTORC2 (IC50 approximately 160 nM and 910 nM, respectively), and inhibits DNA-dependent protein kinase DNA?PK (IC50 approximately 150 nM), while showing markedly lower sensitivity toward VPS34; at the cellular level, by blocking PI3K-mediated conversion of PIP2 to PIP3 and attenuating downstream Akt signaling, while directly acting on mTOR complexes, it enables coordinated regulation at multiple nodes of the PI3K?Akt?mTOR axis. It has been observed to reduce PIP3 generation under epidermal growth factor-stimulated conditions (cellular IC50 approximately 290 nM), and to inhibit phosphorylation of Akt and ribosomal protein S6 (cellular IC50 approximately 250 nM and 120 nM, respectively); in sensitive models, it exhibits in vitro activity against cell proliferation and colony formation in the nanomolar to micromolar range (for example, IC50 values for PC3 cell proliferation and colony formation are approximately 1.8 μM and 270 nM); typical research applications include pathway validation, target engagement and signaling readout experiments, chemical probe benchmarking, exploration of combination regimens with damage response or cytotoxic intervention agents, and functional evaluation of pathway inhibition effects in researcher-defined cell and mouse xenograft models; the concentrations or doses used in experiments generally depend on the specific experimental design and research objectives, and this compound is for laboratory research use only.