2. PI3K/Akt/mTOR
  3. PI3K mTOR
  4. GNE-493

GNE-493 is a potent, selective, and orally available dual pan-PI3-kinase/mTOR inhibitor with IC50s of 3.4 nM, 12 nM, 16 nM, 16 nM and 32 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR.

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

GNE-493 Chemical Structure

GNE-493 Chemical Structure

CAS No. : 1033735-94-2

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10 mM * 1 mL in DMSO
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Customer Review

Based on 2 publication(s) in Google Scholar

GNE-493 Related Antibodies

Top Publications Citing Use of Products

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PI3Kα PI3Kβ PI3Kγ PI3Kδ PI3KC2α PI3KC2β PI3KC2γ Vps34 PI3K PI3KC3 p120γ

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mTOR mTORC1 mTORC2

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

GNE-493 is a potent, selective, and orally available dual pan-PI3-kinase/mTOR inhibitor with IC50s of 3.4 nM, 12 nM, 16 nM, 16 nM and 32 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR.

IC50 & Target[1]

PI3Kα

3.4 nM (IC50)

PI3Kβ

12 nM (IC50)

PI3Kδ

16 nM (IC50)

PI3Kγ

16 nM (IC50)

mTOR

30 nM (IC50)

In Vitro

GNE-493 is a low molecular weight, potent dual inhibitor of pan-PI3 kinases and mTOR. GNE-493 displays approximately equipotent inhibition of Class I PI3K isoforms, is submitted for screening in a 142 kinase panel provided by Invitrogen’s SelectScreen service. Of these kinases, only three are subject to greater than 50% inhibition by GNE-493, and none are inhibited greater than 80% when tested at 1 μM. Subsequently measured IC50s demonstrated that GNE-493 is more than 100-fold selective for PI3Kα over these three unrelated kinases (Aurora A IC50>10 μM, MLK1 IC50=591 nM and SYK IC50=371 nM)[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

GNE-493 Related Antibodies
In Vivo

To confirm and compare in vivo efficacy, GNE-493 is examined in the human MCF7.1 breast cancer xenograft model that harbors a PI3Kα activating mutation. Mice bearing xenografts are dosed orally once daily with 10 mg/kg of GNE-493 for 21 continuous days. Similar to observations made in the PC3 prostate cancer xenograft model, 10 mg/kg of GNE-493 results in 73% tumor growth inhibition at day 21 when compared to vehicle control animals. When achieving comparable levels of drug exposure, GNE-493 shows a similar suppression of the PI3K pathway and consequently, a similar efficacy profile against MCF7.1 breast tumors[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Molecular Weight

372.44

Formula

C17H20N6O2S
CAS No.
Appearance

Solid

Color

Off-white to gray

SMILES

OC(C)(C)C1=CC2=C(S1)C(N3CCOCC3)=NC(C4=CN=C(N)N=C4)=N2
Shipping

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

DMSO : 45 mg/mL (120.82 mM; Need ultrasonic and warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.6850 mL 13.4250 mL 26.8500 mL
5 mM 0.5370 mL 2.6850 mL 5.3700 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

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This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo Dissolution Calculator
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration: mg/mL
Purity & Documentation
References
Kinase Assay
[1]

Enzymatic activity of the Class I PI3K isoforms is measured using a fluorescence polarization assay that monitors formation of the product 3,4,5-inositoltriphosphate molecule as it competes with fluorescently labeled PIP3 for binding to the GRP-1 pleckstrin homology domain protein. An increase in phosphatidyl inositide-3-phosphate product results in a decrease in fluorescence polarization signal as the labeled fluorophore is displaced from the GRP-1 protein binding site. Class I PI3K isoforms are expressed and purified as heterodimeric recombinant proteins. Tetramethylrhodamine-labeled PIP3 (TAMRA-PIP3), di-C8-PIP2, and PIP3 detection reagents are used. PI3K isoforms are assayed under initial rate conditions in the presence of 10 mM Tris (pH 7.5), 25 μM ATP, 9.75 μM PIP2, 5% glycerol, 4 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, 2% (v/v) DMSO at the following concentrations for each isoform: PI3Kα, PI3β at 60 ng/mL; PI3Kγ at 8 ng/mL; PI3Kδ at 45 ng/mL. After assay for 30 min at 25°C, reactions are terminated with a final concentration of 9 mM EDTA, 4.5 nM TAMRA-PIP3, and 4.2 μg/mL GRP-1 detector protein before reading fluorescence polarization on an Envision plate reader. IC50s are calculated from the fit of the dose−response curves to a 4-parameter equation[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
Human prostate cancer PC3 cells are resuspended in Hank’s Balanced Salt Solution and 3×106 cells implanted subcutaneously into the right hind flank of athymic nu/nu (nude) mice. Tumors are monitored until they reached a mean tumor volume of 150-200 mm3 prior to the initiation of dosing. MCF7.1 cells resuspended in a 1:1 mixture of Hank’s Buffered Salt Solution and Matrigel Basement Membrane Matrix, were 5×106 subcutaneously implanted into the right hind flank of athymic nu/nu (nude) mice. Prior to cell inoculation, 17 β-estradiol (0.36 mg/pellet, 60-day release) are implanted into the dorsal shoulder blade area of each nude mouse. After implantation of cells, tumors are monitored until they reached a mean tumor volume of 250-350 mm3 prior to initiating dosing. Female nude (nu/nu) mice that are 6-8 weeks old and weighed 20-30 g are used. Tumor bearing mice are dosed orally daily with 10 mg/kg of GNE-493 for 14 continuous days. Tumor volume is measured in two dimensions (length and width) and is analyzed using Excel version 11.2. Animal body weights are measured. Tumor sizes are recorded twice weekly over the course of the study (14-21 days)

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

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.6850 mL 13.4250 mL 26.8500 mL 67.1249 mL
5 mM 0.5370 mL 2.6850 mL 5.3700 mL 13.4250 mL
10 mM 0.2685 mL 1.3425 mL 2.6850 mL 6.7125 mL
15 mM 0.1790 mL 0.8950 mL 1.7900 mL 4.4750 mL
20 mM 0.1342 mL 0.6712 mL 1.3425 mL 3.3562 mL
25 mM 0.1074 mL 0.5370 mL 1.0740 mL 2.6850 mL
30 mM 0.0895 mL 0.4475 mL 0.8950 mL 2.2375 mL
40 mM 0.0671 mL 0.3356 mL 0.6712 mL 1.6781 mL
50 mM 0.0537 mL 0.2685 mL 0.5370 mL 1.3425 mL
60 mM 0.0447 mL 0.2237 mL 0.4475 mL 1.1187 mL
80 mM 0.0336 mL 0.1678 mL 0.3356 mL 0.8391 mL
100 mM 0.0268 mL 0.1342 mL 0.2685 mL 0.6712 mL
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GNE-493 Related Classifications

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.

Keywords:

GNE-4931033735-94-2GNE493GNE 493PI3KmTORPhosphoinositide 3-kinaseMammalian target of RapamycinInhibitorinhibitorinhibit

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