Home Angiogenesis PI3K inhibitor - mTOR inhibitor Voxtalisib (XL765) For research use only.

Voxtalisib (XL765)

Synonyms: SAR245409

Voxtalisib (SAR245409, XL765) is a dual inhibitor of mTOR/PI3K, mostly for p110γ with IC50 of 9 nM; also inhibits DNA-PK and mTOR. Phase 1/2.

Voxtalisib (XL765) Chemical Structure

Voxtalisib (XL765) Chemical Structure

CAS No. 934493-76-2

Purity & Quality Control

Voxtalisib (XL765) Related Products

Signaling Pathway

PI3K Signaling Pathways

PI3K Signaling Pathway

Biological Activity

Description Voxtalisib (SAR245409, XL765) is a dual inhibitor of mTOR/PI3K, mostly for p110γ with IC50 of 9 nM; also inhibits DNA-PK and mTOR. Phase 1/2.
Targets
PI3Kγ [1]
(Cell-free assay)		 PI3Kα [1]
(Cell-free assay)		 PI3Kδ [1]
(Cell-free assay)		 PI3Kβ [1]
(Cell-free assay)		 DNA-PK [1]
(Cell-free assay)		 Click to View More Targets
9 nM 39 nM 43 nM 113 nM 150 nM
In vitro
In vitro XL765 is active against class I PI3K (IC50 = 39, 113, 9 and 43 nM for p110α, β, γ and δ, respectively). XL765 also inhibits DNA-PK (IC50 = 150 nM) and mTOR (IC50 = 157 nM) but not XL-147 which shows IC50 values of > 15 μM. [1] XL765 treatment results in decreased cell viability in 13 PDA cell lines in a dose-dependent manner. XL765, a dual-target PI3K/mTOR inhibitor, inhibits cell growth and apoptosis in many more cell lines and at lower concentrations as compared to the PI3K-selective inhibitors XL147 and PIK90. The effect can be recapitulated by using combinations of single-targeted compounds. XL765 significantly reduces phosphorylation of the mTOR targets S6, S6K, and 4EBP1, which is associated with greater apoptosis induction rather than to PI3K inhibition alone. XL765 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. [2]
Cell Research Cell lines Pancreatic cancer cell lines (HcG25, Panc89, PA-TU8988T, Panc2.13, MiaPaCa2, Panc10.05, Panc8.13, BxPC-3, etc.)
Concentrations Dissolved in DMSO, final concentration ~10 μM
Incubation Time 24, 48, 72 hours
Method

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.
In Vivo
In vivo The combination of XL765 (30 mg/kg) with chloroquine (50 mg/kg) results in significant inhibition of BxPC-3 xenograft growth in mice models, while XL765 alone at the same dose has no inhibitory effect. [2] Oral administration of XL765 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. XL765 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. [3]
Animal Research Animal Models Female Nu/Nu mice inoculated s.c. with BxPC-3 cells
Dosages 30 mg/kg
Administration Oral gavage once a day
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01596270 Completed
Neoplasm Malignant
Sanofi
 June 2012 Phase 1
NCT01410513 Completed
Indolent Non-Hodgkin Lymphoma|Mantle Cell Lymphoma|Chronic Lymphocytic Leukemia
Sanofi
 December 2011 Phase 1
NCT01240460 Completed
Glioblastoma|Astrocytoma Grade IV
Sanofi
 January 2011 Phase 1

Chemical Information & Solubility

Molecular Weight 270.29 Formula

C13H14N6O
CAS No. 934493-76-2 SDF Download Voxtalisib (XL765) SDF
Smiles CCN1C2=NC(=NC(=C2C=C(C1=O)C3=CC=NN3)C)N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 29 mg/mL ( (107.29 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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