Voxtalisib

SKU: orb1300143

Description

Voxtalisib

Research Area

Molecular Biology, Signal Transduction

Key Properties

• CAS Number: 934493-76-2
• MW: 270.29
• Purity: 98.21%
• Formula: C₁₃H₁₄N₆O
• SMILES: CCn1c2nc(N)nc(C)c2cc(-c2cc[nH]n2)c1=O
• Target: DNA-PK,PI3K,mTOR
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:50 mg/mL (184.99 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (3.7 mM)

Bioactivity

• Target IC50:
  p110α:39 nM|p110γ:9 nM|mTOR:157 nM|DNA-PK:150 nM|p110δ:43 nM|p110β:113 nM|mTORC2:910 nM|mTORC1:160 nM
• In Vivo:
  The combination of Voxtalisib (30 mg/kg) with chloroquine (50 mg/kg) results in significant Inhibition of BxPC-3 xenograft growth in mice models, while Voxtalisib alone a the same dose has no inhibitory effect. Oral administration of Voxtalisib results in greater than 12-fold reduction in median tumor bioluminescence compared to control and improvement in median survival in nude mice implanted intracranially with GBM 39-luc cells. Voxtalisib in combination with temozolomide (TMZ) yields a 140-fold reduction in median bioluminescence with a trend toward improvement in median survival compared with TMZ alone.
• In Vitro:
  Voxtalisib is active against class I PI3K IC50 = 39, 113, 9 and 43 nM for p110α, β, γ and δ, respectively. Voxtalisib also inhibits DNA-PK IC50 = 150 nM) and mTOR IC50 = 157 nM) but not XL-147 which shows IC50 Values of > 15 μM. Voxtalisib treatment results in decreased cell viability in 13 PDA cell lines in a dose-dependent manner. Voxtalisib, a dual-target PI3K/mTOR inhibitor, inhibits cell growth and apoptosis in many more cell lines and at lower concentration as compared to the PI3K Selective inhibitors XL147 and PIK90 the effect can be recapitulated by using combinations of Single-targeted compounds. Voxtalisib significantly reduces phosphorylation o the mTOR targets S6, S6K, and 4EBP1, which is associated with greater apoptosis induction rather than to PI3K Inhibition alone. Voxtalisib treatment causes accumulation of autophagosomes in MIAPaCa-2 cells, and results in significant dose-dependent AVO induction and LC3-II stimulation in MIAPaCa-2 cells stably expressing a LC3-GFP construct.
• Cell Research:
  Cells are treated with XL765 24 hours after plating and Harvested for apoptosis or autophagy assays at 24, 48, or 72 hours after XL765 treatment. Apoptosis is determined by total percentage of annexin V-positive cells by fluorescence-activated cell sorting (FACS). Acidic vesicular organelles (AVOs) are detected in XL765-treated cells by vital staining with acridine orange the degree of AVO formation is expressed as fold increase of acridine orange fluorescence intensity (FL3) in XL765-treated cells versus control cells. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

DNAPK, DNA-PK, inhibit, mTOR, Mammalian target of Rapamycin, Inhibitor, SAR 245409, SAR245409, SAR-245409, Phosphoinositide 3-kinase, PI3K, PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, XL 765, XL765, XL-765, Voxtalisib

Compound Identifiers

PubChem CID

16123056