2. PI3K/Akt/mTOR
  3. PI3K
    mTOR
  4. Voxtalisib

Voxtalisib  (Synonyms: XL765; SAR245409)

Cat. No.: HY-15900 Purity: 98.81%
COA Handling Instructions

Voxtalisib (XL765) is a potent PI3K inhibitor, which has a similar activity toward class I PI3K (IC50s=39, 113, 9 and 43 nM for p110α, p110β, p110γ and p110δ, respectively), also inhibits DNA-PK (IC50=150 nM) and mTOR (IC50=157 nM). Voxtalisib (XL765) inhibits mTORC1 and mTORC2 with IC50s of 160 and 910 nM, respectively.

For research use only. We do not sell to patients.

Voxtalisib Chemical Structure

Voxtalisib Chemical Structure

CAS No. : 934493-76-2

Size Price Stock Quantity
Free Sample (0.1 - 0.5 mg)   Apply Now  
Solution
10 mM * 1 mL in DMSO USD 101 In-stock
Solid + Solvent
10 mM * 1 mL
ready for reconstitution
 USD 101 In-stock
Solid
5 mg USD 92 In-stock
10 mg USD 158 In-stock
25 mg USD 317 In-stock
50 mg USD 502 In-stock
100 mg USD 911 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 4 publication(s) in Google Scholar

Top Publications Citing Use of Products

View All PI3K Isoform Specific Products:

View All Isoforms
PI3Kα PI3Kβ PI3Kγ PI3Kδ PI3KC2α PI3KC2β PI3KC2γ Vps34 PI3K PI3KC3 p120γ

View All mTOR Isoform Specific Products:

View All Isoforms
mTOR mTORC1 mTORC2

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

Voxtalisib (XL765) is a potent PI3K inhibitor, which has a similar activity toward class I PI3K (IC50s=39, 113, 9 and 43 nM for p110α, p110β, p110γ and p110δ, respectively), also inhibits DNA-PK (IC50=150 nM) and mTOR (IC50=157 nM). Voxtalisib (XL765) inhibits mTORC1 and mTORC2 with IC50s of 160 and 910 nM, respectively.

IC50 & Target[1][2]

p110γ

9 nM (IC50)

p110α

39 nM (IC50)

p110δ

43 nM (IC50)

p110β

113 nM (IC50)

mTOR

157 nM (IC50)

mTORC1

160 nM (IC50)

mTORC2

910 nM (IC50)

DNA-PK

150 nM (IC50)

In Vitro

Voxtalisib (XL765) displays potent inhibitory activity against class I PI3K isoforms p110α, p110β, p110δ, and p120γ, with IC50s of 39, 110, 43, and 9 nM, respectively. The IC50 value for inhibition of PI3Kα by Voxtalisib is determined at various concentrations of ATP, revealing Voxtalisib be an ATP-competitive inhibitor with an equilibrium inhibition constant (Ki) value of 13 nM. Voxtalisib also inhibits mTOR (IC50s of 160 and 910 nM for mTORC1 and mTORC2, respectively) in an immune-complex kinase assay and the PI3K-related kinase DNA-PK (IC50 value of 150 nM). In contrast, Voxtalisib (XL765) has relatively weak inhibitory activity toward the class III PI3K vacuolar sorting protein 34 (VPS34; IC50 value of ~9.1 μM). Consistent with its inhibitory activity against purified PI3K proteins, SAR245409 inhibits EGF-induced PIP3 production in PC-3 and MCF7 cells with IC50s of 290 and 170 nM, respectively. The ability of Voxtalisib to inhibit phosphorylation of key signaling proteins downstream of PI3K is examined by assessing its effects on EGF-stimulated phosphorylation of AKT and on nonstimulated phosphorylation of S6 in PC-3 cells by cell-based ELISA. Voxtalisib inhibits these activities with IC50s of 250 and 120 nM, respectively. In MCF7 and PC-3 cells, Voxtalisib inhibits proliferation (monitored by BrdUrd incorporation) with IC50s of 1,070 and 1,840 nM, respectively. To further characterize the effects of Voxtalisib on tumor cell growth, an assay monitoring the anchorage-independent growth of PC-3 and MCF7 cells in soft agar over a 14-day period is used. SAR245409 inhibits colony growth with an IC50 value of 270 nM in PC-3 cells and 230 nM in MCF7 cells[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo

Oral administration of Voxtalisib (XL765) causes a dose-dependent decrease of phosphorylation of AKT, p70S6K, and S6 in the tumors, reaching a maximum of 84% inhibition of S6 phosphorylation at 30 mg/kg at 4 hours. The dose-response relationships derive from the 4 hours time point predict 50% inhibition of AKT, p70S6K, and S6 phosphorylation to occur at doses of 19 mg/kg (pAKTT308 and pAKTS473), 51 mg/kg (p-p70S6K), and 18 mg/kg (pS6). Inhibition of AKT, p70S6K, and S6 phosphorylation in MCF7 tumors following a 30 mg/kg dose of Voxtalisib is maximal at 4 hours, reaching 61% to 84%; however, the level of inhibition decreases to 0% to 42% by 24 hours, and minimal or no inhibition is evident by 48 hours. Following a 100 mg/kg dose of Voxtalisib, inhibition is also maximal at 4 hours (52%-75%)[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
Molecular Weight

270.29

Appearance

Solid

Formula

C13H14N6O
CAS No.
SMILES

O=C1C(C2=NNC=C2)=CC3=C(C)N=C(N)N=C3N1CC
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 10 mg/mL (37.00 mM; Need ultrasonic)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 3.6997 mL 18.4986 mL 36.9973 mL
5 mM 0.7399 mL 3.6997 mL 7.3995 mL
10 mM 0.3700 mL 1.8499 mL 3.6997 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 1 mg/mL (3.70 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 1 mg/mL (3.70 mM); Clear solution

  • 3.

    Add each solvent one by one:  10% DMSO    90% corn oil

    Solubility: ≥ 1 mg/mL (3.70 mM); Clear solution

*All of the co-solvents are available by MCE.
Purity & Documentation

Purity: 98.81%

COA (248 KB) LCMS (274 KB)

Handling Instructions (2659 KB)
References
Cell Assay
[2]

Cellular proliferation is assessed using the Cell Proliferation ELISA, Bromodeoxyuridine Chemiluminescence Kit. Cytotoxicity is assessed using the ATP Bioluminescence Assay as follows: PC-3, MCF7, A549, LS174T, MDA-MB-468, U87-MG, and OVCAR-3 cells are plated at densities of 7×103, 1.5×104, 6×103, 7×103, 7×103, 6×103, 1.5×104 cells per well, respectively, onto 96-well microtiter plates in culture medium, incubated at 37°C, 5% CO2 for 18 hours, and then treated with a serial dilution of compound in medium containing a final concentration of 0.3% DMSO. Triplicate wells are used for each compound concentration. Control wells receive 0.3% DMSO in media. Cultures are incubated at 37°C, 5% CO2 for an additional 24 hours and cells are then assayed for viability using the ViaLight HS Kit[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[2]

Mice[2]
In vivo efficacy studies are performed in athymic nude mice. Tumor cells are cultured in DMEM supplemented with 10% FBS (20% for PC-3 and OVCAR-3 cells), Penicillin-Streptomycin, and nonessential amino acids at 37°C in a humidified 5% CO2 atmosphere. On day 0, cells are harvested by brief trypsinization, and 1 to 5×106 cells in 0.1 mL ice-cold Hanks Balanced Salt Solution are implanted subcutaneously (OVCAR-3) or intradermally (MCF7 and U-87 MG) into the hind flank of female athymic nude mice. In the case of the MCF7 model, an estrogen pellet (IRA) is implanted subcutaneously at the nape of neck at the time of tumor cell implantation. A total of 3×106 PC-3 cells are similarly harvested and implanted subcutaneously into the hind-flank of 5- to 8-week-old male nude mice. Tumor growth is monitored weekly with calipers until staging and dose initiation. During the dosing period, body and tumor weights are assessed. Voxtalisib (XL-765) is formulated in sterile water/10 mM HCl or water and administered at the indicated doses and regimens by oral gavage at a dose volume of 10 mL/kg.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.
Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

  • Molarity Calculator

  • Dilution Calculator

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass   Concentration   Volume   Molecular Weight *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
× = ×
C1   V1   C2   V2

Keywords:

Voxtalisib934493-76-2XL765 SAR245409XL 765XL-765SAR245409SAR 245409SAR-245409PI3KmTORPhosphoinositide 3-kinaseMammalian target of RapamycinInhibitorinhibitorinhibit

Your Recently Viewed Products:

Inquiry Online

Your information is safe with us. * Required Fields.

Product Name

  

Salutation

Applicant Name *

 

Email address *

Phone number *

 

Organization name *

Department *

 

Requested quantity *

Country or Region *

      

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
Voxtalisib
Cat. No.:
HY-15900
Quantity:
MCE Japan Authorized Agent:

Customer Review

Thank You for Your Feedback!

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

Product Name

  

Lot #

Applicant Name *

 

Email address *

Phone number

 

Department *

Organization name *

 

Country or Region *

Remarks

Request for HNMR Report

We have received your request and will respond to you as soon as possible.