K-756

Name: K-756
Brand: MedChemExpress
SKU: HY-U00422
Rating: 5.0 (2 reviews)

Cat. No.: HY-U00422 Purity: 99.25%: FAQs
Data Sheet SDS COA Handling Instructions

Molarity Calculator

K-756 is a direct and selective tankyrase (TNKS) inhibitor, which inhibits the ADP-ribosylation activity of TNKS1 and TNKS2 with IC₅₀s of 31 and 36 nM, respectively.

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

K-756 Chemical Structure

CAS No. : 130017-40-2

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 143	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 143	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 130	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 210	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 720	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 1150	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 2 publication(s) in Google Scholar

2 Publications Citing Use of MCE K-756

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View All Isoforms

PARP PARP1 PARP2 PARP3 PARP4 TNKS1/PARP5A TNKS2/PARP5B PARP7 PARP10 PARP14 PARP15 PARP12 PARP16

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

K-756 is a direct and selective tankyrase (TNKS) inhibitor, which inhibits the ADP-ribosylation activity of TNKS1 and TNKS2 with IC₅₀s of 31 and 36 nM, respectively.

IC₅₀ & Target^[1]

TNKS1

31 nM (IC₅₀)

TNKS2

36 nM (IC₅₀)

In Vitro

K-756 is a novel and selective Wnt/β-catenin pathway inhibitor targeting tankyrase (TNKS). TNKS is one of the members of the PARP family (it is also known as PARP5). K-756 binds to the induced pocket of TNKS and inhibits its enzyme activity. To study the isoform selectivity of K-756, the PARP family enzyme inhibitory activity at 10 μM is evaluated. K-756 inhibits TNKS1 and TNKS2 by 97% and 100%, respectively. In contrast, the inhibitory activity of K-756 against PARP1, PARP2, PARP3, PARP6, PARP7, and PARP11 is less than 13%. K-756 inhibits the cell growth of APC-mutant colorectal cancer COLO 320DM and SW403 cells by inhibiting the Wnt/β-catenin pathway. K-756 strongly inhibits the reporter activity in DLD-1/TCF-Luc cells with an IC₅₀ of 110 nM, but does not inhibit DLD-1/mtTCF-Luc cells, even at 1,000 nM. APC-mutant colorectal cancer cell line COLO 320DM and SW403 cells are treated with K-756 and after 144 hours, cell growth inhibition is measured by an XTT assay. The application of K-756 inhibits the cell growth of COLO 320DM with a GI₅₀ of 780 nM. K-756 also inhibits SW403 with a GI₅₀ of 270 nM^[1].

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

In Vivo

DLD-1/TCF-Luc cell xenografts are created in SCID mice. Vehicle (0.5% MC400) or K-756 is administered orally once a day for 3 days at 100, 200, and 400 mg/kg. The Wnt/β-catenin signal inhibition in the tumor is detected by measuring FGF20 and LGR5 and luciferase activity. The expression of FGF20 and reporter activity are significantly decreased at doses of 100 mg/kg and above at 3-day administration. The expression of LGR5 is significantly decreased at doses of 200 mg/kg and above at 3-day administration. The maximum inhibitory activity is reached with the administration of K-756 at a dose of 400 mg/kg at 3-day administration. The Wnt/β-catenin signal inhibition at a dose of 400 mg/kg is observed from 1-day administration^[1].

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

Molecular Weight

433.50

Formula

C₂₄H₂₇N₅O₃

CAS No.

130017-40-2

Appearance

Solid

Color

White to off-white

SMILES

O=C1NC2=C(C=CC=C2)CN1CC3CCN(C4=C5C=C(OC)C(OC)=CC5=NC=N4)CC3

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 : 4.55 mg/mL (10.50 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	2.3068 mL	11.5340 mL	23.0681 mL
5 mM	0.4614 mL	2.3068 mL	4.6136 mL
10 mM	0.2307 mL	1.1534 mL	2.3068 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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator
Dilution Calculator

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

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 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 0.46 mg/mL (1.06 mM); Clear solution

This protocol yields a clear solution of ≥ 0.46 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (4.6 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 0.46 mg/mL (1.06 mM); Clear solution

This protocol yields a clear solution of ≥ 0.46 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 (4.6 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 3

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 0.45 mg/mL (1.04 mM); Clear solution

This protocol yields a clear solution of ≥ 0.45 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (4.5 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.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

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: 99.25%

Select Batch:

Data Sheet (283 KB) SDS (251 KB)

COA (254 KB) HNMR (285 KB) LCMS (96 KB)

Handling Instructions (2659 KB)

References

[1]. Okada-Iwasaki R, et al. The Discovery and Characterization of K-756, a Novel Wnt/β-Catenin Pathway Inhibitor Targeting Tankyrase. Mol Cancer Ther. 2016 Jul;15(7):1525-34. [Content Brief]

Kinase Assay ^[1]	The activity of each enzyme is measured using a PARP1, PARP2, PARP3, PARP6, PARP7, and PARP11 Chemiluminescent Assay Kit, and a TNKS1 and TNKS2 Histone Ribosylation Assay Kit. Enzymatic reactions are conducted in duplicate at 30°C for 1 hour in a 50 μL mixture containing an assay buffer, an enzyme-coated plate, and a substrate. After the enzymatic reactions, 50 μL of Streptavidin-HRP is added to each well and the plate is incubated at room temperature for an additional 30 minutes. 100 μLs of developer reagents are added to the wells and luminescence is measured using a Synergy2 microplate reader. The luminescence data are analyzed using the GraphPad Prism software program^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay ^[1]	For the cell viability assay, APC-mutant colorectal cancer cell line COLO 320DM and SW403 cells are seeded in 96-well white plates. siRNAs are reverse transfected by RNAiMax. After 144 hours, a cell viability assay is performed using a Cell Titer-Glo Luminescent Cell Viability Assay Kit. Luciferase activity is measured using a Top count NXT system. For the cell growth inhibition assay, cells are seeded in 96-well plates. The next day, the cells are treated with the compounds (e.g., K-756, 0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM and 10 μM). After 0, 72, or 144 hours of incubation, XTT reagent is added to the cells. After 3 hours of incubation, the formation of formazan dye from tetrazolium salt XTT is measured using a SpectraMax 340PC system^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	Mice^[1] SCID mice (CB17/Icr-Prkdc^scid/CrlCrlj, male, 5 weeks old) are subcutaneously implanted with 5×10⁶ cells of DLD-1/TCF-Luc cells. After 13 days, the mice with a tumor volume of 236.38 to 595.80 mm³ are divided into groups of 5 animals. On the day after grouping, 0.5% MC 400 or K-756 (100, 200, and 400 mg/kg) is orally administered to the mice once a day for 3 days. Twenty-four hours after the last administration of first and second day and 25 hours after the last administration of the third day, the tumor tissues are collected from the mice and frozen in liquid nitrogen. Tumor total RNA is extracted using an RNeasy mini Kit and reverse-transcribed using VILO reagent. An RT-PCR is performed. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Okada-Iwasaki R, et al. The Discovery and Characterization of K-756, a Novel Wnt/β-Catenin Pathway Inhibitor Targeting Tankyrase. Mol Cancer Ther. 2016 Jul;15(7):1525-34. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.3068 mL	11.5340 mL	23.0681 mL	57.6701 mL
	5 mM	0.4614 mL	2.3068 mL	4.6136 mL	11.5340 mL
	10 mM	0.2307 mL	1.1534 mL	2.3068 mL	5.7670 mL

K-756 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:

K-756130017-40-2K756K 756PARPpoly ADP ribose polymeraseInhibitorinhibitorinhibit

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K-756

Customer Review

K-756 Related Antibodies

2 Publications Citing Use of MCE K-756

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Biological Activity

Protocol

Purity & Documentation

References

Customer Review

K-756 Related Antibodies

Molarity Calculator

Dilution Calculator

Complete Stock Solution Preparation Table

K-756 Related Classifications

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