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Voxtalisib (XL765) Analogue

Name: Voxtalisib (XL765) Analogue
Brand: Selleck Chemicals
SKU: S1523
Rating: 5 (6 reviews)

Catalog No.S1523 Synonyms: SAR245409

For research use only.

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.

Voxtalisib (XL765) Analogue Chemical Structure

CAS No. 1349796-36-6

Selleck's Voxtalisib (XL765) Analogue has been cited by 6 Publications

3 Customer Reviews

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PI3K Signaling Pathway Map

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]	Click to View More Targets
9 nM	39 nM	43 nM	113 nM	150 nM	Click to View More Targets

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 Research:

^[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 Research:

^[2]

Animal Models: Female Nu/Nu mice inoculated s.c. with BxPC-3 cells
Dosages: 30 mg/kg
Administration: Oral gavage once a day

References

Solubility (25°C)

In vitro	DMSO	12 mg/mL (20.01 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 30% PEG400+0.5% Tween80+5% propylene glycol For best results, use promptly after mixing. Click to purchase: PEG400 Tween 80	30 mg/mL

Chemical Information

Molecular Weight	599.66
Formula	C₃₁H₂₉N₅O₆S
CAS No.	1349796-36-6
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC1=C(C=C(C=C1)C(=O)NC2=CC=C(C=C2)S(=O)(=O)NC3=NC4=CC=CC=C4N=C3NC5=CC(=CC(=C5)OC)OC)OC

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In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 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
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Molarity Calculator

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Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
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

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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