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SML2376

Sigma-Aldrich

GSK′963

≥98% (HPLC)

Synonyme(s) :

1-[(5S)-4,5-Dihydro-5-phenyl-1H-pyrazol-1-yl]-2,2-dimethyl-1-propanone; 2,2-Dimethyl-1-(5(S)-phenyl-4,5-dihydro-pyrazol-1-yl)-propan-1-one, GSK 963, GSK′ 963A, GSK′963A, GSK-963, GSK-963A, GSK963, GSK963A

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About This Item

Formule empirique (notation de Hill):
C14H18N2O
Numéro CAS:
2049868-46-2
Poids moléculaire :
230.31
Code UNSPSC :
12352200
Nomenclature NACRES :
NA.77

Pureté

≥98% (HPLC)

Forme

powder

Couleur

white to beige

Solubilité

DMSO: 2 mg/mL, clear

Température de stockage

2-8°C

Chaîne SMILES 

O=C(C(C)(C)C)N1[C@H](C2=CC=CC=C2)CC=N1

Actions biochimiques/physiologiques

GSK′963 (GSK′963A) is a brain-penetrant, highly potent and selective ATP site-targeting receptor-interacting protein 1 kinase (RIP1; RIPK1) inhibitor (IC50 = 0.8-8 nM with 50 μM ATP; IC50 >10 μM against RIPK2/3/5 and 335 other kinases) that protects against TNFα/zVAD-induced necroptosis (EC50 = 1/4 nM in mouse L929/human U937 cultures) and blocks Y. pestis-induced death of murine fetal liver macrophages (1 μM). GSK′963 prevents lethal hypothermia by acute sterile shock (2 mg/kg i.p. 15 min prior to TNFα/zVAD i.v.) and protects against acute neuronal death upon autologous blood intracerebral hemorrhage induction in mice in vivo (25 mg/kg/3 hr i.p.).

Code de la classe de stockage

11 - Combustible Solids

Classe de danger pour l'eau (WGK)

WGK 3

Point d'éclair (°F)

Not applicable

Point d'éclair (°C)

Not applicable

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Sevda Lule et al.
Stroke, 48(9), 2549-2556 (2017-08-03)
Recent studies using cultured cells and rodent intracerebral hemorrhage (ICH) models have implicated RIPK1 (receptor interacting protein kinase-1) as a driver of programmed necrosis and secondary injury based on use of chemical inhibitors. However, these inhibitors have off-target effects and
Hongyan Guo et al.
Cell host & microbe, 17(2), 243-251 (2015-02-13)
Herpes simplex virus (HSV)-1 and HSV-2 are significant human pathogens causing recurrent disease. During infection, HSV modulates cell death pathways using the large subunit (R1) of ribonucleotide reductase (RR) to suppress apoptosis by binding to and blocking caspase-8. Here, we demonstrate
Anne von Mässenhausen et al.
Cell death & disease, 9(3), 359-359 (2018-03-04)
Receptor-interacting protein kinases 1 and 3 (RIPK1/3) have best been described for their role in mediating a regulated form of necrosis, referred to as necroptosis. During this process, RIPK3 phosphorylates mixed lineage kinase domain-like (MLKL) to cause plasma membrane rupture.
Wenjing Liu et al.
Proceedings of the National Academy of Sciences of the United States of America, 115(7), E1475-E1484 (2018-02-01)
Tubular cell necrosis is a key histological feature of acute kidney injury (AKI). Necroptosis is a type of programed necrosis, which is executed by mixed lineage kinase domain-like protein (MLKL) upon its binding to the plasma membrane. Emerging evidence indicates
Mohammad Ali et al.
Cell death & disease, 9(3), 346-346 (2018-03-03)
Proteasome inhibitors have achieved clinical success because they trigger intrinsic and extrinsic cell death to eliminate susceptible human cancers. The ubiquitin-proteasome protein degradation system regulates signaling pathways by controlling levels of components such as cellular inhibitor of apoptosis (cIAP)1 and
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