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Merck
CN

SML4220

GPR34 Antagonist, T8848

≥98% (HPLC)

Synonym(s):

N-[(2E)-3-(4′-Chloro[1,1′-biphenyl]-4-yl)-1-oxo-2-propen-1-yl]-O-(phenylmethyl)tyrosine, (E)-3-(4-(Benzyloxy)phenyl)-2-(3-(4′-chloro-[1,1′-biphenyl]-4-yl)acrylamido)propanoic acid, T 8848, T-8848

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About This Item

Empirical Formula (Hill Notation):
C31H26ClNO4
CAS Number:
Molecular Weight:
512.00
MDL number:
NACRES:
NA.21
Assay:
≥98% (HPLC)
Form:
powder
Quality level:
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assay

≥98% (HPLC)

form

powder

color

white to beige

solubility

DMSO: 2 mg/mL, clear

storage temp.

2-8°C

Quality Level

Application

GPR34 Antagonist, T8848 may be used to investigate the effects of pharmacological inhibition of GPR34 on microglial dysfunction and neuroinflammation in Alzheimer’s disease (AD) mouse models.

Biochem/physiol Actions

GPR34 antagonist that potently inhibits neuroinflammation by blocking PI3K-AKT and ERK pathways, selectively reducing cytokine release.The GPR34 antagonist T8848 selectively targets G-protein coupled receptor 34 (GPR34), inhibiting LysoPS and myelin debris-induced IL-1β and IL-6 expression in microglia with high specificity. In vitro, T-8848 is applied at of 100 μg/mL, effectively reducing pro-inflammatory cytokine release. In vivo, at 10 mg/kg (i.p.) administered over 18-days in C57BL/6J mice and Gpr34-specific knockout mice (e.g., Gpr34fl/flCx3cr1CreER), it lessens neuroinflammation, demyelination, and tissue damage in models of multiple sclerosis and stroke. Mechanistically, T 8848 blocks GPR34-mediated phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) and extracellular signal-regulated kinase (ERK) pathways, suppressing downstream inflammatory gene expression and cytokine release.

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Torsten Schöneberg et al.
Pharmacology & therapeutics, 189, 71-88 (2018-04-24)
Research on GPR34, which was discovered in 1999 as an orphan G protein-coupled receptor of the rhodopsin-like class, disclosed its physiologic relevance only piece by piece. Being present in all recent vertebrate genomes analyzed so far it seems to improve
Jiaxian Yan et al.
Nature immunology, 25(11), 2057-2067 (2024-10-03)
Type 1 innate lymphoid cells (ILC1s) are a class of tissue-resident cells with antitumor activity, suggesting its possible role in solid tumor immune surveillance, but it is not clear whether manipulating ILC1s can induce potent antitumor immune responses. Here, we
Bolong Lin et al.
Cellular & molecular immunology, 21(10), 1131-1144 (2024-07-20)
Sterile neuroinflammation is a major driver of multiple neurological diseases. Myelin debris can act as an inflammatory stimulus to promote inflammation and pathologies, but the mechanism is poorly understood. Here, we showed that lysophosphatidylserine (LysoPS)-GPR34 axis played a critical role

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