1346546-69-7 Usage
Description
N-5-benzothiazolyl-6-[(1-methylethyl)sulfonyl]-4-Quinolinamine, also known as GSK'872, is a potent and selective inhibitor of receptor activating protein kinase 3 (RIP3) with an IC50 of 1.3 nM. It exhibits over 1000-fold selectivity for RIP3 over a panel of 300 other kinases, including RIP1. GSK872 is capable of preventing necroptosis, virus-induced necrosis, and TLR3-induced necrosis. At higher concentrations (3 10 μM), it can also induce Caspase8-mediated apoptosis.
Uses
Used in Pharmaceutical Industry:
N-5-benzothiazolyl-6-[(1-methylethyl)sulfonyl]-4-Quinolinamine is used as a potent and selective RIP3 inhibitor for preventing necroptosis, virus-induced necrosis, and TLR3-induced necrosis. Its high selectivity and potency make it a valuable compound for the development of therapeutic agents targeting RIP3-related diseases and conditions.
Used in Research Applications:
In research settings, N-5-benzothiazolyl-6-[(1-methylethyl)sulfonyl]-4-Quinolinamine serves as a valuable tool for studying the role of RIP3 in various cellular processes, including necroptosis and apoptosis. Its ability to selectively inhibit RIP3 allows researchers to investigate the specific functions and mechanisms of this kinase in different biological systems.
Biological Activity
GSK'872 (GSK2399872A) is a potent and selective RIP3 kinase inhibitor which binds RIP3 kinase domain with high affinity (IC50=1.8 nM) and inhibits kinase activity with IC50 of 1.3 nM. It has minimal cross-reactivity.
in vitro
When assayed at 1 μM, GSK'872 fails to inhibit most of 300 human protein kinases tested. It fails to inhibit RIP1 kinase when tested directly. GSK'872 blocks TNF-induced necroptosis in a concentration-dependent manner in HT-29 cells. In cell-based assays, there is a 100- to 1000-fold shift in the IC50 compared to the cell-free biochemical assays. GSK'872 also blocks necroptosis in primary human neutrophils isolated from whole blood. GSK'872 inhibits TLR3- or DAI-induced death, two RIP1-independent pathways of necroptosis. It induces caspase activation followed by apoptotic cell death.
in vivo
GSK'872 treatment significantly decreases HIF-1α expression compared with no treatment after ischemia injury in vivo.
References
1)?Kaiser et al. (2013) Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL; J. Biol. Chem.?288 31279
2)?Mandal et al. (2014) RIP3 induces apoptosis independent of pro-necrotic kinase activity; Mol. Cell 56 481
Check Digit Verification of cas no
The CAS Registry Mumber 1346546-69-7 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,3,4,6,5,4 and 6 respectively; the second part has 2 digits, 6 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 1346546-69:
(9*1)+(8*3)+(7*4)+(6*6)+(5*5)+(4*4)+(3*6)+(2*6)+(1*9)=177
177 % 10 = 7
So 1346546-69-7 is a valid CAS Registry Number.
1346546-69-7Relevant articles and documents
AMINO-QUINOLINES AS KINASE INHIBITORS
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Paragraph 0186; 0187, (2015/09/23)
Disclosed are quinoline compounds having the formula: wherein R1, R2 and A are as defined herein, and methods of making and using the same.
