Antibodies
SAR245409 (XL765)
- 貨號 Cat. No.
- S1523
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
SAR245409 (XL765)
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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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | 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 | mTOR | p110α | p110β | p110γ | p110δ | |
| IC50 | 157 nM | 39 nM | 113 nM | 9 nM | 43 nM [1] | |
| 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] | |||||
| Features | ||||||
Protocol(Only for Reference)
Cell Assay: [2]
| Cell lines | Pancreatic cancer cell lines (HcG25, Panc89, PA-TU8988T, Panc2.13, MiaPaCa2, Panc10.05, Panc8.13, BxPC-3, etc.) |
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| 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 |
| Solubility | 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00485719 | Completed | Cancer | Sanofi | 2007-06 | Phase 1 |
| NCT00704080 | Completed | Mixed Gliomas|Malignant Gliomas|Glioblastoma Multiforme | Sanofi | 2008-08 | Phase 1 |
| NCT00777699 | Completed | Cancer|Non-Small Cell Lung Cancer | Sanofi | 2008-08 | Phase 1 |
| NCT01082068 | Completed | Breast Cancer | Sanofi | 2010-06 | Phase 1|Phase 2 |
| NCT01240460 | Completed | Glioblastoma|Astrocytoma, Grade IV | Sanofi | 2011-01 | Phase 1 |
Chemical Information
Download SAR245409 (XL765) SDF
| Molecular Weight (MW) | 599.66 |
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| Formula | C31H29N5O6S |
| CAS No. | 1349796-36-6 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 12 mg/mL (20 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 30% PEG400/0.5% Tween80/5% propylene glycol, | 30 mg/mL | |
| * <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. | |||
| Chemical Name | Benzamide, N-[4-[[[3-[(3,5-dimethoxyphenyl)amino]-2-quinoxalinyl]amino]sulfonyl]phenyl]-3-methoxy-4-methyl- |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.59966 | 5.9966 | 11.9932 | - |
Customer Reviews (3)
 Click to enlarge | Rating | |
| Source | Endocrinology, 2013, 154(3), 1247-59. SAR245409 (XL765) purchased from Selleck | |
| Method | Serum GH and PRL secretion assay | |
| Cell Lines | female nude mice | |
| Concentrations | 25 mg/kg | |
| Incubation Time | ||
| Results | The TMZ/XL765 combination decreased both serum rat-GH and rat-PRL dramatically compared with either agent alone. |
Product Citations (1)
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
