GSK'963

Catalog No.S8642 Batch:S864201

Technical Data

Formula

C₁₄H₁₈N₂O

Molecular Weight

230.31

CAS No.

2049868-46-2

Solubility (25°C)*

In vitro

DMSO

200 mg/mL (868.39 mM)

Ethanol

46 mg/mL (199.73 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O

10.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 200 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

GSK'963 is a chiral small-molecule inhibitor of RIP1 kinase (RIPK1) with an IC50 of 29 nM in FP binding assays. It is >10 000-fold selective for RIP1 over 339 other kinases.

Targets

RIP1 kinase ^[1]
(Cell-free assay)

29 nM

In vitro

GSK'963 inhibits RIP1-dependent cell death with an IC50 of between 1 and 4 nM in human and murine cells^[1].

In vivo

GSK'963 is a potent inhibitor of a TNF+zVAD-mediated lethal shock. At 2 mg/kg, GSK'963 would maintain blood concentrations above the concentration required for 90% inhibition of RIP1 activity for an extended period of time compared with Nec-1^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines BMDM Concentrations 100 nM Incubation Time 30 min Method For immunoblot analysis, BMDM pretreated with GSK'963 (100 nM), GSK'962 (100 nM) or Nec-1 (10 μM) for 30 min, are stimulated with 50 ng/ml TNF for 5 and 15 min. Lysates prepared in 1× Cell Lysis Buffer containing protease and phosphatase inhibitors are separated on 4-12% SDS-PAGE and blotted onto nitrocellulose membrane. Blots are probed for IκB, phospho-IκB, and tubulin as a loading control.
Animal Study:^{^[1]}	Animal Models C57BL/6 mice Dosages 0.2, 2 and 10 mg/kg Administration i.p.

Cell Assay:^{^[1]}

Cell lines
BMDM
Concentrations
100 nM
Incubation Time
30 min
Method
For immunoblot analysis, BMDM pretreated with GSK'963 (100 nM), GSK'962 (100 nM) or Nec-1 (10 μM) for 30 min, are stimulated with 50 ng/ml TNF for 5 and 15 min. Lysates prepared in 1× Cell Lysis Buffer containing protease and phosphatase inhibitors are separated on 4-12% SDS-PAGE and blotted onto nitrocellulose membrane. Blots are probed for IκB, phospho-IκB, and tubulin as a loading control.

Animal Study:^{^[1]}

Animal Models
C57BL/6 mice
Dosages
0.2, 2 and 10 mg/kg
Administration
i.p.

References

[1] Berger SB, et al. Cell Death Discov. 2015, 1:15009.

Selleck's GSK'963 has been cited by 5 publications

Bacillus cereus cereolysin O induces pyroptosis in an undecapeptide-dependent manner [ Cell Death Discov, 2024, 10(1):122]	PubMed: 38458999
Polyunsaturated fatty acids-induced ferroptosis suppresses pancreatic cancer growth [ Sci Rep, 2024, 14(1):4409]	PubMed: 38388563
RIPK1 is essential for Herpes Simplex Virus-triggered ZBP1-dependent necroptosis in human cells [ bioRxiv, 2024, 2024.09.17.613393]	PubMed: 39345610
Toxoplasma gondii secreted effectors co-opt host repressor complexes to inhibit necroptosis [ Cell Host Microbe, 2021, S1931-3128(21)00192-X]	PubMed: 34043960
The MK2/Hsp27 axis is a major survival mechanism for pancreatic ductal adenocarcinoma under genotoxic stress [ Sci Transl Med, 2021, 13(622):eabb5445]	PubMed: 34851698

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.