Voxtalisib (XL765) Analogue

Catalog No.S1523 Batch:S152301

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Technical Data

Formula

C31H29N5O6S
Molecular Weight 599.66 CAS No. 1349796-36-6
Solubility (25°C)* In vitro DMSO 15 mg/mL (25.01 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Voxtalisib (SAR245409, XL765) Analogue 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] PI3Kα [1] PI3Kδ [1] PI3Kβ [1] DNA-PK [1] View More
9 nM 39 nM 43 nM 113 nM 150 nM
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]
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 (from reference)

Cell Assay:

[2]
  • 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.
Animal Study:

[2]
  • Animal Models

    Female Nu/Nu mice inoculated s.c. with BxPC-3 cells

  • Dosages

    30 mg/kg

  • Administration

    Oral gavage once a day

Customer Product Validation

Data from [Endocrinology, 2013, 154, 1247-59]

Data from [Endocrinology, 2013, 154, 1247-59]

, , Dr. Zhang of Tianjin Medical University

Selleck's Voxtalisib (XL765) Analogue has been cited by 7 publications

The PI3K/mTOR dual inhibitor GSK458 potently impedes ovarian cancer tumorigenesis and metastasis. [ Cell Oncol (Dordr), 2020, 8] PubMed: 32382996
Identification of a Non-Gatekeeper Hot Spot for Drug-Resistant Mutations in mTOR Kinase [Wu TJ, et al. Cell Rep, 2015, 11(3):446-59] PubMed: 25865887
mTOR inhibition potentiates HSP90 inhibitor activity via cessation of HSP synthesis [Acquaviva J, et al. Mol Cancer Res, 2014, 12(5):703-13] PubMed: 24554781
Deciphering combinations of PI3K/AKT/mTOR pathway drugs augmenting anti-angiogenic efficacy in vivo [ PLoS One, 2014, 9(8):e105280] PubMed: 25144531
Deciphering Combinations of PI3K/AKT/mTOR Pathway Drugs Augmenting Anti-Angiogenic Efficacy In Vivo [Sasore T, et al PLoS One, 2014, 9(8):e105280] PubMed: 25144531
A chemical biology approach identified PI3K as a potential therapeutic target for neurofibromatosis type 2. [Petrilli AM, et al. Am J Transl Res, 2014, 6(5):471-493]
Inhibition of PI3K/AKT/mTOR Pathway Enhances Temozolomide-Induced Cytotoxicity in Pituitary Adenoma Cell Lines in Vitro and Xenografted Pituitary Adenoma in Female Nude Mice. [Dai C, et al. Endocrinology, 2013, 154(3):1247-59] PubMed: 23384836

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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