2. PI3K/Akt/mTOR
  3. PI3K
  4. CNX-1351

CNX-1351 is a potent and isoform-selective targeted covalent PI3Kα inhibitor with IC50 of 6.8 nM.

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

CNX-1351 Chemical Structure

CNX-1351 Chemical Structure

CAS No. : 1276105-89-5

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 152 In-stock
Solution
10 mM * 1 mL in DMSO USD 152 In-stock
Solid
1 mg USD 40 In-stock
5 mg USD 120 In-stock
10 mg USD 190 In-stock
25 mg USD 412 In-stock
50 mg USD 660 In-stock
100 mg USD 1050 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 1 publication(s) in Google Scholar

CNX-1351 Related Antibodies

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

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

CNX-1351 is a potent and isoform-selective targeted covalent PI3Kα inhibitor with IC50 of 6.8 nM.

IC50 & Target[1]

PI3Kα

6.8 nM (IC50)

PI3Kβ

166 nM (IC50)

PI3Kδ

240.3 nM (IC50)

PI3Kγ

3020 nM (IC50)

In Vitro

CNX-1351 is able to potently (EC50<100 nM) and specifically inhibit signaling in PI3Kα-dependent cancer cell lines, and this leads to a potent antiproliferative effect (GI50<100 nM). CNX-1351 inhibits PI3K signaling in SKOV3 cells, with potency (EC50 of 10-100 nM) similar to that of the pan-PI3K inhibitor. To investigate the functional consequence of inhibiting PI3Kα in cells, two cell lines with different PIK3CA activating mutations, SKOV3 ovarian cancer cells (H1047R) and MCF-7 breast cancer cells (E545K), are treated with CNX-1351 and growth is monitored. Both PIK3CA-driven cell lines are growth inhibited by exposure to CNX-1351 for 96 h (GI50 of 78 and 55 nM, respectively)[1].

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

CNX-1351 Related Antibodies
In Vivo

CNX-1351 inhibits p-AktSer473 in mouse spleens and bonds to PI3Kα in vivo. CNX-1351 is delivered into the intraperitoneal cavity of nude mice at 100 mg/kg once a day for 5 consecutive days (n=3 mice per group). Spleens are harvested from the mice at the indicated times after the last dose (1-24 h) and interrogated by immunoblot for P-AktSer473 or for PI3Kα occupancy. Inhibition of PI3K signaling is detected as a decrease in P-AktSer473 at 1 and 4 h after last dose[1].

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

573.71

Formula

C30H35N7O3S
CAS No.
Appearance

Solid

Color

White to yellow

SMILES

C/C(C)=C/C(CCC(N1CCN(CC2=CC3=NC(C4=CC=CC5=C4C=NN5)=NC(N6CCOCC6)=C3S2)CC1)=O)=O
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 : 100 mg/mL (174.30 mM; Need ultrasonic; 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 1.7430 mL 8.7152 mL 17.4304 mL
5 mM 0.3486 mL 1.7430 mL 3.4861 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

  • Dilution Calculator

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

Mass
=
Concentration
×
Volume
×
Molecular Weight *

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

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

    Solubility: ≥ 2.5 mg/mL (4.36 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (4.36 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.88%

COA (247 KB) HNMR (197 KB) RP-HPLC (216 KB)

Handling Instructions (2659 KB)
References
Kinase Assay
[1]

CNX-1351 is tested in a panel of 10 lipid kinases. CNX-1351s tested in a 10-concentration IC50 curve with 3-fold serial dilution starting at 1 μM. Reactions are carried out at 10 μM ATP. An HTRF assay format is used for PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ; ADP-GLO assay format is used for other kinases. The following substrates are used: for HTRF, phosphatidylinositol 4,5-bisphosphate; for SPHK1 and SPHK2, sphingosine; for other ADP-GLO enzymes, phosphatidylinositol. For general kinase selectivity, CNX-1351 is run in a kinase selectivity panel at using HotSpot technology and radioisotope-based P81 filtration. CNX-1351 is dissolved in pure DMSO to the final 1 μM test concentration. Substrates for the various kinases tested against CNX-1351 are prepared fresh daily in reaction buffer. Any required cofactors are then added to the substrate solution followed by kinase addition and preincubated for 30 min at room temperature. 33P-ATP (10 μM) is delivered into the reaction mixture to initiate the reaction, and reaction continued for 2 h at room temperature. The reaction is terminated, and any unreacted phosphate is washed away using 0.1% phosphoric acid prior to detection utilizing a proprietary technology. The study is performed in duplicate, and 10 μM staurosporine, a nonselective, ATP-competitive kinase inhibitor, is used as the positive control[1].

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

SKOV3 cells or MCF-7 cells are plated in SKOV3 proliferation assay medium (DMEM supplemented with 5-10% FBS and pen/strep) at a density of 5000 cells in 180 μL volume per well in Costar no. 3610 white 96-well clear flat-bottom plates and incubated overnight in a humidified 37°C incubator. A standard curve ranging from 10 000 to 50 000 cells is set up in a separate plate and allowed to adhere to the plate for 4-6 h, at which time the plate is developed using Cell Titer-Glo. The next morning, 3-fold compound dilutions ranging from 10 000 to 40 nM are prepared in proliferation medium containing 1% DMSO. Then 20 μL of each dilution is added to the SKOV3 or MCF-7 cells plated the previous day, resulting in a dose-response curve from 1000 to 4 nM. The cells are incubated for 96 h and then developed with Cell Titer Glo. The cell numbers at the end of the assay are determined using the standard curve generated at the start of the assay. Growth inhibition is calculated using the following formulas, and GI50 values are determined[1].

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

Mice[1]
Female nu/nu (n=3/group) are administered compound (GDC-0941 or CNX-1351) delivered ip at 100 mg/kg once daily for 5 consecutive days. After delivery of the last dose, spleens from treated animals are harvested at 1, 4, and 24 h time points. Spleens are immediately frozen in liquid nitrogen. Samples are stored at -80°C until processing for homogenates. Homogenates are made by adding approximately 100 μL of spleen sample to a Precellys homogenizing tube containing 300 μL of cell extraction buffer plus Complete protease inhibitor and PhosStop phosphatase inhibitor and kept on ice. The sample is homogenized in a Precellys 24 homogenizer for 15 s followed by centrifugation at 16000g for 20 min at 4°C. The supernatant is moved to a new tube, and the protein concentration is determined by BCA Assay.

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 1.7430 mL 8.7152 mL 17.4304 mL 43.5760 mL
5 mM 0.3486 mL 1.7430 mL 3.4861 mL 8.7152 mL
10 mM 0.1743 mL 0.8715 mL 1.7430 mL 4.3576 mL
15 mM 0.1162 mL 0.5810 mL 1.1620 mL 2.9051 mL
20 mM 0.0872 mL 0.4358 mL 0.8715 mL 2.1788 mL
25 mM 0.0697 mL 0.3486 mL 0.6972 mL 1.7430 mL
30 mM 0.0581 mL 0.2905 mL 0.5810 mL 1.4525 mL
40 mM 0.0436 mL 0.2179 mL 0.4358 mL 1.0894 mL
50 mM 0.0349 mL 0.1743 mL 0.3486 mL 0.8715 mL
60 mM 0.0291 mL 0.1453 mL 0.2905 mL 0.7263 mL
80 mM 0.0218 mL 0.1089 mL 0.2179 mL 0.5447 mL
100 mM 0.0174 mL 0.0872 mL 0.1743 mL 0.4358 mL
  • 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.

CNX-1351 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:

CNX-13511276105-89-5CNX1351CNX 1351PI3KPhosphoinositide 3-kinaseInhibitorinhibitorinhibit

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:
CNX-1351
Cat. No.:
HY-16596
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.