Voxtalisib (XL765) Analogue

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

For research use only.

Catalog No.S1523 Synonyms: SAR245409

6 publications

Voxtalisib (XL765) Analogue Chemical Structure

Molecular Weight(MW): 599.66

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.

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

Cell Oncol (Dordr), 2020, 8

PubMed: 32382996 ( click the link to review the publication )

Cell Rep, 2015, 11(3):446-59

PubMed: 25865887 ( click the link to review the publication )

Mol Cancer Res, 2014, 12(5):703-13

PubMed: 24554781 ( click the link to review the publication )

Am J Transl Res, 2014, 6(5):471-493

PubMed: ( click the link to review the publication )

PLoS One, 2014, 9(8):e105280

PubMed: 25144531 ( click the link to review the publication )

Endocrinology, 2013, 154(3):1247-59

PubMed: 23384836 ( click the link to review the publication )

3 Customer Reviews

The TMZ/XL765 combination decreases serum GH and PRL of mice bearing GH3 xenografts. A and B, After treatment with DMSO, TMZ, XL765, or the XL765/TMZ combination, the blood of the nude mice xenograft with GH3 tumor was collected and serum rat-GH and rat-PRL were measured by IRMA (TMZ/XL765 combination vs TMZ or XL765 alone: ***P <.001).

Endocrinology 2013 154, 1247-59. Voxtalisib (XL765) Analogue purchased from Selleck.

TMZ, XL765, or the TMZ/XL765 combination treatment inhibits the cell proliferation and induces the cell apoptosis of GH3 cells in vivo. A and B, Ki-67 expression in the section of GH3 tumors treated with DMSO, TMZ, XL765, or the TMZ/XL765 combination was determined by IHC. Positive cells appear brown, whereas negative cells remain blue (n=10 tumors per group). Magnification, ?0 as indicated. CTRL, control. C and D , The apoptotic cells of tumor tissues from various treatments were detected by TUNEL staining. TUNEL-positive cells appear brown, whereas negative cells remain blue (n =10 tumors per group). Magnification, ?40 as indicated. (TMZ/XL765 combination vs TMZ or XL765 alone; *** P<0.001).

Endocrinology 2013 154, 1247-59. Voxtalisib (XL765) Analogue purchased from Selleck.
After starved in serum-free medium for 24 h, A549 cells incubated with the indicated concentrations of XL765 for 3 h,followed by 20-minute stimolation of 100ng/ml EGF.

Dr. Zhang of Tianjin Medical University. Voxtalisib (XL765) Analogue purchased from Selleck.

Purity & Quality Control

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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	View More

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

Cell Research:

^[2]

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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.

(Only for Reference)

Animal Research:

^[2]

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

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.	30 mg/mL

* 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 Download Voxtalisib (XL765) Analogue SDF

Molecular Weight	599.66
Formula	C₃₁H₂₉N₅O₆S
CAS No.	1349796-36-6
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	SAR245409
Smiles	COC1=CC(=CC(=C1)NC2=NC3=CC=CC=C3N=C2N[S](=O)(=O)C4=CC=C(NC(=O)C5=CC=C(C)C(=C5)OC)C=C4)OC

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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Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)

% DMSO+ % + % Tween 80+ % ddH₂O

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Calculation results:

Working concentration： mg/ml；

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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，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 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).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

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 (data from https://clinicaltrials.gov, updated on 2020-05-15)

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

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.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

PI3K Signaling Pathway Map

PI3K Inhibitors with Unique Features

Selective PI3K Inhibitors

CAL-101 (Idelalisib, GS-1101) : p110δ-selective, IC50=2.5 nM.
Selective PI3K Inhibitors

TGX-221 : p110β-specific, IC50=5 nM.
Most Potent PI3K Inhibitor

BEZ235 (NVP-BEZ235, Dactolisib) : p110α/γ/δ/β, IC50=4 nM/5 nM/7 nM/75 nM.
FDA-approved PI3K Inhibitor

CAL-101 (Idelalisib, GS-1101) : Approved by FDA for Relapsed Chronic Lymphocytic Leukemia, Follicular Lymphoma and Small Lymphocytic Lymphoma.
Newest PI3K Inhibitor

VS-5584 (SB2343) ^New : Potent and selective dual PI3K/mTOR inhibitor for mTOR, PI3Kα/β/δ/γ with IC50 of 3.4 nM and 2.6-21 nM, respectively.

Related PI3K Products

Taselisib (GDC 0032) ^New

Taselisib (GDC 0032) is a potent, next-generation β isoform-sparing PI3K inhibitor targeting PI3Kα/δ/γ with K_i of 0.29 nM/0.12 nM/0.97nM, >10 fold selective over PI3Kβ.

Features:A beta isoform-sparing PI3K inhibitor.
Pilaralisib (XL147) ^New

Pilaralisib (XL147) is a selective and reversible class I PI3K inhibitor for PI3Kα/δ/γ with IC50 of 39 nM/36 nM/23 nM in cell-free assays, less potent to PI3Kβ. Phase 1/2.
GNE-317 ^New

GNE-317 is a potent, brain-penetrant PI3K inhibitor.
LY294002

LY294002 is the first synthetic molecule known to inhibit PI3Kα/δ/β with IC50 of 0.5 μM/0.57 μM/0.97 μM, respectively; more stable in solution than Wortmannin, and also blocks autophagosome formation. It not only binds to class I PI3Ks and other PI3K-related kinases, but also to novel targets seemingly unrelated to the PI3K family. LY294002 also inhibits CK2 with IC50 of 98 nM. LY294002 is a non-specific DNA-PKcs inhibitor and activates autophagy and apoptosis.
3-Methyladenine (3-MA)

3-Methyladenine (3-MA) is a selective PI3K inhibitor for Vps34 and PI3Kγ with IC50 of 25 μM and 60 μM in HeLa cells; blocks class I PI3K consistently, whereas suppression of class III PI3K is transient, and also blocks autophagosome formation. 3-Methyladenine (3-MA) is successfully used to suppress mitophagy. Solutions of 3-MA are best fresh-prepared by heating.
Idelalisib (CAL-101, GS-1101)

Idelalisib (CAL-101, GS-1101) is a selective p110δ inhibitor with IC50 of 2.5 nM in cell-free assays; shown to have 40- to 300-fold greater selectivity for p110δ than p110α/β/γ, and 400- to 4000-fold more selectivity to p110δ than C2β, hVPS34, DNA-PK and mTOR. Idelalisib also stimulates autophagy.
Wortmannin

Wortmannin is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Wortmannin blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays. Wortmannin also inhibits PLK1 activity.
Dactolisib (BEZ235)

Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3^TopBP1-ER cell. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2.
Buparlisib (BKM120)

Buparlisib (BKM120, NVP-BKM120) is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM in cell-free assays, respectively. Reduced potency against VPS34, mTOR, DNAPK, with little activity to PI4Kβ. Buparlisib induces apoptosis. Phase 2.
Pictilisib (GDC-0941)

Pictilisib (GDC-0941) is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). Pictilisib (GDC-0941) induces autophagy and apoptosis. Phase 2.

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Voxtalisib (XL765) Analogue