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Merck
모든 사진(1)

주요 문서

SML2376

Sigma-Aldrich

GSK′963

≥98% (HPLC)

동의어(들):

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

실험식(Hill 표기법):
C14H18N2O
CAS Number:
Molecular Weight:
230.31
UNSPSC 코드:
12352200
NACRES:
NA.77

분석

≥98% (HPLC)

양식

powder

색상

white to beige

solubility

DMSO: 2 mg/mL, clear

저장 온도

2-8°C

SMILES string

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

생화학적/생리학적 작용

Brain-penetrant, highly potent and selective RIPK1 (RIP1) inhibitor with necroptosis blocking efficacy in vitro and in vivo.
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.).

Storage Class Code

11 - Combustible Solids

WGK

WGK 3

Flash Point (°F)

Not applicable

Flash Point (°C)

Not applicable


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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
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
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.
Mallary C Greenlee-Wacker et al.
Blood, 129(24), 3237-3244 (2017-05-06)
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes infections associated with extensive tissue damage and necrosis. In vitro, human neutrophils fed CA-MRSA lyse by an unknown mechanism that is inhibited by necrostatin-1, an allosteric inhibitor of receptor-interacting serine/threonine kinase 1 (RIPK-1). RIPK-1
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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

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