Voxtalisib (XL765)
For research use only.
Catalog No.S7646 Synonyms: SAR245409
9 publications
CAS No. 934493-76-2
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.
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HL60, HL60/ADR, K562 and K562/A02 cells pretreated with various concentrations of Voxtalisib (0, 0.625, 1.25, 2.5, 5 and 10 μM) for 48 h were harvested for western blot. The levels of cyclin D1, p27, and p-pRb in the nuclei were determined.
Biomed Pharmacother, 2018, 103:1069-1078. Voxtalisib (XL765) purchased from Selleck.
Cell viability measurements. The IMR-32, LA-N-1 and CHP‑134 cells were treated with mTOR/PI3K inhibitor SAR245409 alone or in combination with the 14G2a mAb (40 μg/ml) for 72 h. The cell viability was determined by measuring ATP content, and compared to respective controls treated with appropriate diluents (DMSO or water, set as 1). P-values for t-test were as follows: *p<0.05, **p<0.01, ***p<0.001.
Int J Oncol, 2015, 47(3):1143-59. . Voxtalisib (XL765) purchased from Selleck.
Purity & Quality Control
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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. | |||||||||||
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| Targets |
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| 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] |
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| 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] |
Protocol
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Solubility (25°C)
| In vitro | DMSO | 54 mg/mL (199.78 mM) |
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| Water | Insoluble | |
| Ethanol | Insoluble |
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Information
| Molecular Weight | 270.29 |
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| Formula | C13H14N6O |
| CAS No. | 934493-76-2 |
| Storage |
powder in solvent |
| Synonyms | SAR245409 |
| Smiles | CCN1C2=NC(=NC(=C2C=C(C1=O)C3=CC=NN3)C)N |
In vivo Formulation Calculator (Clear solution)
| Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment) | ||||||||||
| Dosage | mg/kg |  |
Average weight of animals | g | |
Dosing volume per animal | ul | |
Number of animals | |
| Step 2: Enter the in vivo formulation () | ||||||||||
| % DMSO % % Tween 80 % ddH2O | ||||||||||
| CalculateReset | ||||||||||
Calculation results:
Working concentration： mg/ml；
Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL，)
Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH2O，mix and clarify.
1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
Bio Calculators
Molarity Calculator
Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:
Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)
*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).
Dilution Calculator
Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
Molecular Weight Calculator
Enter the chemical formula of a compound to calculate its molar mass and elemental composition:
Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2
Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
Molarity Calculator
Clinical Trial Information
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
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| NCT01596270 | Completed | Drug: SAR245409 | Neoplasm Malignant | Sanofi | June 2012 | Phase 1 |
| NCT01410513 | Completed | Drug: SAR245409 | Indolent Non-Hodgkin Lymphoma|Mantle Cell Lymphoma|Chronic Lymphocytic Leukemia | Sanofi | December 2011 | Phase 1 |
| NCT01240460 | Completed | Drug: XL765 (SAR245409)|Drug: XL147 (SAR245408) | Glioblastoma|Astrocytoma Grade IV | Sanofi | January 2011 | Phase 1 |
Tech Support
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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