microglial

PLX5622 is an orally active small-molecule CSF1R inhibitor that selectively depletes microglia in the brains of mice and rats. It is commonly used to establish models related to microglia-associated neuroinflammation, neurodegenerative diseases (such as Alzheimer's disease and Parkinson's disease), brain injury, and neuroimmune regulation. This product is also available as a premixed diet version (C2005 PLX5622 in AIN-76A Diet (1200 ppm)), eliminating the need for self-preparation and offering superior stability and reproducibility.

Edicotinib (JNJ-527) is a blood-brain-penetrating, orally active, selective CSF-1R inhibitor (IC50 value is 3.2 nM), with less inhibitory effects on KIT (IC50 value is 20 nM) and FLT3 (IC50 value is 190 nM). Edicotinib (JNJ-527) can block microglial proliferation and attenuate neurodegeneration, and can be used to study Alzheimer's disease and rheumatoid arthritis.

Geranylgeraniol (FT0626663) is an isoprenoid found in fruits, vegetables, and grains, including rice. Geranylgeraniol (FT0626663) inhibits growth and induces apoptosis of various tumor cells. Geranylgeraniol (FT0626663) protects monocytes against statin-induced cytotoxicity and suppresses the growth of Mycobacterium.

Mulberrofuran C, a benzofuran present in Morus alba, has inhibitory effects on Aβ₁₋₄₂ auto-aggregation, tau protein aggregation, AChE, antioxidant activity and neuroprotective effects, and has anti-Alzheimer's disease potential.

MAO-B-IN-8 is a highly potent and reversible inhibitor of monoamine oxidase-B (MAO-B), also inhibiting microglial production of neuroinflammatory mediators. This compound is specifically designed for research on neurodegenerative diseases [1].

CHPG is a selective mGluR5 agonist that reduces LDH release and neuronal apoptosis, activates the ERK and Akt pathways, and protects against traumatic brain injury. It also increases the number of differentiated human OPCs and alleviates LPS-induced inflammation.

PLX5622 hemifumarate is a highly selective, blood-brain barrier-permeable, and orally active CSF1R inhibitor with an IC50 of 0.016 μM and a Ki of 5.9 nM. It can be used to eliminate proliferating and specific microglia before and during disease progression and is applicable for inducing Alzheimer's disease models.

AZD8797 (KAND567) is an orally available, selective and potent human CX3CR1-converting antagonist with inhibitory effects on CX3CR1 and CXCR2, and potentially protects against SARS-CoV-2-induced neuronal damage, preventing worsening of nociceptive sensitization and microglial activation in a migraine model of rats following seizures.

YM-I-26 is a selective inhibitor of the NLRP3 inflammasome. This compound enhances the phagocytic activity of β-amyloid in murine microglial BV2 cells and reduces the production of IL-1β and IL-10. YM-I-26 is useful for research into inflammation-related immunomodulatory activities.

AChE/BChE-IN-23 (Compound 6e) is a dual inhibitor of acetylcholinesterase and butyrylcholinesterase, exhibiting IC50 values of 0.91 μM for AChE, 1.19 μM for eqBChE, and 1.01 μM for hBChE. This compound also demonstrates antioxidant properties and inhibits the aggregation of Aβ1-42 and Tau proteins. Moreover, AChE/BChE-IN-23 prevents the activation of microglial cells by inhibiting the release of reactive oxygen species and mitochondrial damage. Additionally, it reduces the levels of the NLRP3 inflammasome in human microglial cells and reverses memory impairment in mice induced by scopolamine.

TFGF-18 is a GSK-3β inhibitor with an IC50 of 0.59 μM. It suppresses microglial activation and the release of pro-inflammatory mediators induced by LPS by inhibiting GSK-3β and downstream p65/NF-κB signaling. TFGF-18 also prevents neuronal apoptosis and oxidative stress, reduces the expression of Bax, caspase-3, and cleaved-caspase-3, while increasing Bcl-2 expression. It offers neuroprotection by inhibiting neuroinflammation and alleviating cognitive impairment.

BET-IN-21 (compound 16) is a BET (Bromo and Extra-Terminal domain) inhibitor capable of penetrating the blood-brain barrier, with a Ki value of 230 nM. It suppresses microglial activation and demonstrates therapeutic effects in mice with experimental autoimmune encephalomyelitis.

TREM2 agonist-3 (Compound 4i) is a direct TREM2 agonist (Kd=19.0 µM), and its Kd value for TREM1 is 39.8 µM. It induces Syk phosphorylation and enhances microglial cell phagocytosis, and can be used for the study of neurodegenerative diseases.

10-Butyl EtherMinocycline is a derivative of Minocycline and acts as an inhibitor of MMP-8 and MMP-9, with IC50 values of 69.4 µM and 47.0 µM, respectively. It exhibits negligible antibacterial activity against E. coli, S. typhi, and C. albicans. Additionally, 10-Butyl EtherMinocycline inhibits LPS-induced microglial activation and VEGF-induced endothelial cell migration, as well as L-Glutamine-induced ROS levels. This compound significantly reduces alcohol consumption in a chronic intermittent ethanol (CIE) mouse model and is utilized in studies related to neuroinflammation and alcohol use disorder (AUD).

TREM2 agonist-5 is a ligand for the microglial lipid-sensing receptor (TREM2) and acts as an agonist with a Kd of 71.36 μM. It is the racemic analog of the TREM2 agonist VG-3927 and demonstrates excellent microglial phagocytic activity in HEK293-hTREM2/DAP12 cells, effectively activating TREM2 signaling. TREM2 agonist-5 has superior in vitro pharmacokinetics compared to VG-3927 and is potentially useful for Alzheimer's disease research.

BAL-1516 is a brain-penetrant and highly selective NLRP3 inhibitor (IC50=14.2 nM). It significantly inhibits the release of interleukin-1β and interleukin-18 in microglial neuroinflammation models (IC50=11-59 nM). BAL-1516 holds potential for research in neurodegenerative diseases, such as Alzheimer's and Parkinson's, as well as systemic inflammatory disorders.

FPR2 agonist 5 is a selective agonist of formyl peptide receptor 2 (FPR2). It induces Ca2+ mobilization in HL60 cells transfected with FPR2, demonstrating an EC50 value of 1.2 μM, and causes FPR2 desensitization with an IC50 of 0.32 μM. Additionally, FPR2 agonist 5 exhibits neuroprotective effects by reducing LDH release, NO production, and the levels of IL-1β, IL-6, IL-33, and IL-10 in LPS-induced primary microglial cells from mice. It is utilized in research related to neuroinflammatory and inflammatory diseases.

T2M-010 is a potent TREM2 agonist capable of crossing the blood-brain barrier (Kd= 0.83 μM). It activates receptor proximal signaling pathways, induces SYK phosphorylation in TREM2-expressing cells, and enhances phagocytosis in microglia. T2M-010 is applicable for research on protective microglial responses associated with Alzheimer's disease (AD).

Aβ aggregation-IN-3 (Compound B7) is an inhibitor of Aβ aggregation. It prevents the aggregation of Aβ and exhibits protective effects in both neuronal and microglial cell models. Additionally, Aβ aggregation-IN-3 alleviates Aβ-induced paralysis in Caenorhabditis elegans and can ameliorate symptoms associated with Alzheimer's disease.

Ganglioside GT1b bovine trisodium is a trisialoganglioside that binds to botulinum toxin type A (BTxA), BTxA heavy chain, and tetanus toxin with IC50 values of 11, 0.74, and 7.2 μM, respectively. It acts as a TLR2 agonist in spinal cord microglia, leading to microglial activation, increased expression of pro-inflammatory factors, and heightened pain sensitivity. Additionally, Ganglioside GT1b bovine trisodium reduces the production of IL-6, IL-10, IgG, IgM, and IgA in human peripheral blood mononuclear cells (PBMC). In neuronal cell models, it elevates extracellular glutamate levels. Ganglioside GT1b bovine trisodium is used in the research of immune and neurological disorders.

Aβ aggregation-IN-5 is an inhibitor of β-amyloid (amyloid-β) aggregation that can penetrate the blood-brain barrier. It prevents Aβ aggregation/oligomerization, rescues cells damaged by Aβ/ROS toxicity, and reduces microglial activation and nitric oxide (NO) production. In APP/PSEN1 mouse models, Aβ aggregation-IN-5 decreases amyloid burden, neuroinflammation, and microglial activation. This compound is used in Alzheimer's disease research.

YHV98-4 is a selective Hv1 channel (Hv1 channel) inhibitor that can cross the blood-brain barrier. It specifically inhibits the Hv1 channel with a half-maximal inhibitory concentration of 1 µM without affecting other ion channels. YHV98-4 decreases the spread of p-tau, enhances ATP production, and promotes microglial mitophagy. By inhibiting the Hv1 channel and reducing ROS production, it alleviates inflammatory pain. Additionally, YHV98-4 enhances the transfer of mitochondria (mitochondria) from microglia to neurons, aiding in the delivery of functional mitochondria, thereby repairing neuronal damage and improving cognitive function. It mitigates inflammation and is applicable in Alzheimer’s disease research.

PROTACBRD3 degrader-1 (compound D072) is a potent and selective PROTACBRD3 degrader. It specifically degrades BRD3 in mice, leading to downregulation of H3K18ac expression without affecting BRD2 or BRD4. This compound reduces intraocular inflammation in an experimental autoimmune uveitis (EAU) mouse model and inhibits pro-inflammatory microglia in both uveitis retinas and LPS-treated mouse microglial cell line BV2. PROTACBRD3 degrader-1 is applicable for uveitis research.

T-5342126 is a toll-like receptor 4 (TLR4) antagonist that reduces LPS-induced production of nitric oxide (NO) in RAW 264.7 cells (IC50 = 27.8 μM) and decreases LPS-induced IL-8, TNF-α, and IL-6 production in isolated human whole blood (IC50s = 110.5, 315.6, and 318.4 μM, respectively). T-5342126 (82 mg/kg) also reduces ethanol intake and the abundance of ionized calcium-binding adapter molecule 1 (Iba1), a marker of microglial activation, in the central nucleus of the amygdala in ethanol-dependent mice.