GPR34 agonist 1
GPR34 agonist 1 is a G-protein coupled receptor 34 agonist that enhances fibrillar Aβ uptake in mouse primary microglia with an EC50 of 5 nM.GPR34 agonist 1 selectively activates Gi/o-coupled GPR34, reduces intracellular cyclic adenosine monophosphate levels, and requires functional TREM2 signaling.GPR34 agonist 1 induces microglial Aβ fibril phagocytosis and chemotaxis, enhances microglial uptake and clearance of amyloid β fibrils, and increases microglial Aβ fibril uptake in vivo and in human induced pluripotent stem cell-derived microglia.GPR34 agonist 1 can be used for the research of Alzheimer disease.
For research use only. We do not sell to patients.
- CAS No.: 2459994-71-7
- Formula: C30H36NO11P
- Molecular Weight:617.58
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
GPR34 5 nM (EC50, Aβ uptake assay in mouse primary microglia) |
In Vitro
GPR34 agonist 1 (0.1-100 nM; 1.5-7.5 h) specifically enhances fibrillar Aβ uptake by mouse primary microglia in a concentration- and time-dependent manner, with an EC50 of 5 nM, without affecting uptake of soluble Aβ species or other phagocytic substrates[1].
GPR34 agonist 1 (10 nM) reduces intracellular cAMP levels in mouse primary microglia, which reverses forskolin-mediated suppression of fibrillar Aβ uptake[1].
GPR34 agonist 1 (10-100 nM; 4.5 h) enhances fibrillar Aβ uptake by human iPSC-derived microglia-like cells, with significant activity at 100 nM[1].
GPR34 agonist 1 potently activates human GPR34 expressed in HEK293A cells, with key interactions mediated by hydrophilic pocket residues and the L-shaped hydrophobic pocket formed by L2235·43[2].
GPR34 agonist 1 (1-10 μM; overnight) binds to human GPR34 in a stable conformation, engaging both hydrophilic and hydrophobic binding pockets, and forms a high-resolution GPR34-Gi complex suitable for structural analysis[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
GPR34 agonist 1 (250 µM; intrahippocampal; single injection) does not enhance microglial amyloid β uptake in Tyrobp-deficient NL-G-F Alzheimer's disease mice, indicating the effect requires functional TREM2 signaling[1].
GPR34 agonist 1 (500 µM; intracerebroventricular; continuous infusion; 4 weeks) does not alter hippocampal amyloid β burden in 9-month-old NL-G-F Alzheimer's disease mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:AppNL-G-F (NL-G-F) (15-17 months old, male and female)[1]
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Dosage:250 µM
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Administration:intrahippocampal; single injection
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Result:Increased the percentage of MX04-positive microglia from a mean of ~7% (vehicle) to a mean of ~14%.
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Animal Model:AppNL-G-F (NL-G-F) (9 months old)[1]
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Dosage:500 µM
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Administration:intracerebroventricular; continuous infusion; 4 weeks
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Result:Detected no significant differences in Aβ40 or Aβ42 levels between treated and vehicle-treated mice across TBS-soluble, Triton X-100-soluble, SDS-soluble, and formic acid-soluble hippocampal fractions.
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Animal Model:Tyrobp−/−, AppNL-G-F (NL-G-F) (male and female)[1]
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Dosage:250 µM
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Administration:intrahippocampal; single injection
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Result:Did not increase the percentage of MX04-positive microglia; levels remained comparable between treated and vehicle-treated hippocampi.
Chemical Information
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CAS No. 2459994-71-7
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Molecular Weight 617.58
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Formula C30H36NO11P
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SMILES
OC([C@@H](N)COP(O[C@H](COCC)COC(CCC(C=CC=C1)=C1OCC2=CC(OC3=CC=CC=C3)=CC=C2)=O)(O)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Phagocytosis Functional Assay
A phagocytosis functional assay measures the ability of phagocytic cells, such as neutrophils, macrophages, monocytes, or microglia/macrophages, to bind and internalize particulate targets including bacteria, yeast particles, beads, or myelin particles. Fluorescent flow-cytometry assays detect target uptake as fluorescence associated with gated phagocytes, while pH-sensitive dyes such as pHrodo increase signal in acidic phagosomal compartments and therefore preferentially report internalized particles rather than particles remaining outside the cell. Microscopy or high-content imaging can be used to confirm intracellular localization and, in some protocols, to follow uptake kinetics.
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Cell migration
Cell migration is a method that plays an important role in wound healing, cell differentiation, embryonic development, etc.
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Chemotaxis Gradient Chamber Assay 1
The chemotaxis gradient chamber assay is based on the principle of observing directional cell migration in response to a stable, linear or quasi-linear concentration gradient of a chemoattractant formed between two fluid reservoirs separated by a narrow observation chamber. Cells placed within the chamber respond to the gradient by polarized movement toward higher chemoattractant concentrations, allowing quantification of chemotactic behavior in real time under microscopy. The classic Zigmond chamber design enables simultaneous visualization of gradient formation and individual cell trajectories, making it suitable for studying leukocyte chemotaxis and other motile cell types in vitro.
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Under-Agarose Cell Migration Assay
The under-agarose cell migration assay is a classical in vitro chemotaxis method designed to evaluate directed cell movement through a semi-solid agarose matrix toward soluble chemoattractant gradients, enabling visualization and quantification of leukocyte or motile cell migration in a confined 2D-like environment. In this system, cells and chemoattractants are placed in separate wells cut into an agarose gel, allowing diffusion-driven gradient formation that guides directional migration, which is typically assessed by measuring migration distance, cell morphology changes, and accumulation toward the chemoattractant source. This assay has been widely used to study neutrophil and leukocyte chemotaxis as a simple alternative to filter-based migration systems and allows direct microscopic observation of migrating cells under near-physiological confinement conditions.
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Transwell/Boyden Chamber Migration Assay
The Transwell/Boyden chamber migration assay measures cell movement through a porous membrane separating an upper and lower chamber, usually after a chemoattractant gradient is established by placing cells in the upper chamber and chemoattractant-containing medium in the lower chamber. The readout is generated by quantifying cells that traverse the membrane and appear on the lower membrane surface or in the lower chamber, depending on whether the cell type is adherent or non-adherent. This assay reflects chemotactic or haptotactic migration rather than matrix invasion unless an extracellular-matrix barrier is added to the membrane.
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Protocol for Pharmacokinetic Study
Pharmacokinetic studies quantify how an organism handles a drug over time through absorption, distribution, metabolism, and excretion, and the core experimental readout is the concentration-time profile of parent drug and, when relevant, metabolites in biological matrices such as plasma, whole blood, urine, bile, or tissue. Pharmacokinetic analysis links dose, route, exposure, clearance, half-life, distribution, bioavailability, and systemic exposure to drug efficacy and toxicity hypotheses rather than measuring a signaling pathway directly. The literature links pharmacokinetics to drug-development phenotypes by showing that drug metabolism and pharmacokinetics influence compound progression, exposure-response interpretation, safety margins, dosing strategy, and failure risk during discovery and development. DMPK science contributes to compound optimization by integrating physicochemical properties, in vitro metabolism, transporter behavior, in vivo exposure, and pharmacodynamic contex
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Chemotaxis Gradient Chamber Assay 2
Chemotaxis gradient chamber assays measure directional cell migration in response to a soluble chemical gradient by imaging cells as they move across a defined observation region; the readout is generated from time-lapse cell trajectories, displacement toward the gradient, forward migration index, trajectory plots, rose/polar plots, and statistical tests of non-random directionality. The Dunn chamber is a direct-viewing glass chamber in which cells migrate across a bridge between control and chemoattractant wells, allowing observation of cells in a linear concentration gradient; related direct-viewing formats include the Insall chamber, which supports defined unidirectional gradients and high numerical-aperture microscopy, and the μ-Slide Chemotaxis chamber, which supports long-term live-cell imaging and gradient characterization with fluorescent dye.
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Amyloid: Congo Red Amyloid Staining
Congo red amyloid staining is a histochemical method used to detect extracellular amyloid deposits in tissue sections based on the affinity of Congo red dye for β-pleated sheet-rich protein aggregates. When bound to amyloid, Congo red produces characteristic apple-green birefringence under polarized light microscopy, which is widely regarded as a diagnostic feature of amyloid deposition in histopathology. The diagnostic principle relies on the combination of dye binding (congophilia) and optical anisotropy under polarized illumination, which distinguishes amyloid from most non-amyloid eosinophilic extracellular deposits in routine histological evaluation. Amyloid identification by Congo red staining remains a cornerstone in diagnostic pathology despite the availability of adjunct methods such as immunohistochemistry and mass spectrometry, particularly because of its ability to localize deposits directly within tissue architecture. The specificity of Congo red-positive deposits is incre
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Alzheimer’s Disease Modeling
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive functions and loss of specific types of neurons and synapses. Alzheimer's symptoms can be simulated in mice by injecting drugs (such as Aβ) or genetically modified.
Purity & Documentation
References
[1]. Etani H, et al. Selective agonism of GPR34 stimulates microglial uptake and clearance of amyloid β fibrils. Alzheimer's research & therapy. 2025 Nov 20;17(1):248. [Content Brief]
[2]. Izume T, et al. Structural basis for lysophosphatidylserine recognition by GPR34. Nature communications. 2024 Feb 07;15(1):902. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Keywords
- GPR34 agonist 1
- 2459994-71-7
- Orphan GPCR
- TREM2 signaling
- Gi/o-coupled GPR34
- intracellular cyclic adenosine monophosphate
- HEK293A cells
- NL-G-F Alzheimer's disease mice
- microglial Aβ fibril phagocytosis
- mouse primary microglia
- human induced pluripotent stem cell-derived microglia
- G-protein coupled receptor 34
- Alzheimer disease
- Inhibitor
- inhibitor
- inhibit