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.

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.

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.

Nargenicin is a macrolide antibiotic that selectively inhibits the growth of S. aureus, methicilin resistant S. aureus (MRSA), and M. luteus (MICs = 0.6, 0.3, and 2.5 μg/ml, respectively) over a panel of 11 Gram-positive and Gram-negative bacteria (MICs = >80 μg/ml). [1] It dose-dependently inhibits S. aureus DnaE in the presence of DNase I-activated DNA and E. coli DnaE when used at concentrations of 0.00001-0.1 and 0.01-100 μg/mL, respectively. [2] In murine BV-2 microglial cells, nargenicin (1 μM) inhibits cytokine expression and nitric oxide production induced by LPS.[3] Nargenicin (200 μM), when used in combination with 1,25-dihydroxyvitamin D3 or all-trans retinoic acid , reduces cell proliferation by 37-47% and increases cell differentiation by 82-85% in HL-60 human myeloid leukemia cells.[4]

MMP-9 inhibitor I is an inhibitor of matrix metalloproteinase-9 (MMP-9) that is selective over MMP-1 and MMP-13 (IC50s = 5, 1,050, and 113 nM, respectively). It also decreases the activity of TNF-α converting enzyme (TACE) in a dose-dependent manner (IC50 = 0.54 μM). MMP-9 inhibitor I decreases TNF-α secretion stimulated by LPS in BV-2 microglial cells when used at concentrations of 50 and 100 μM.

Potent and selective CB2 receptor agonist (Ki = 12.8 nM; EC50 = 38.67 nM). Exhibits negligible affinity for the CB1 receptor (Ki > 40,000 nM) and no activity at the GPR55. Suppresses neuroinflammation by reducing microglial activation in a multiple sclerosis mouse model. BBB permeable; anti-inflammatory and neuroprotective.

Jaceosidin has anti-oxidative activity. Jaceosidin has anti-inflammatory activity, also a microglial inhibitor with anti-neuroinflammation activity. aceosidin has anticancer activity, modulates the ERK/ATM/Chk1/2 pathway, leading to inactivation of the Cd

Shanzhiside methylester reduces neuropathic pain by activating spinal GLP-1 receptors and subsequently stimulating microglial β-endorphin expression via the p38 MAPK signaling.

Poloxamer 188 is a nonionic triblock copolymer surfactant and bioactive excipient used as a medical excipient to exacerbate cerebral amyloidosis, presynaptic dystrophy, and pathogenic microglial cell activation in 5XFAD mice.

1. beta-Asarone (Cis-Isoelemicin) may be a potential preventive drug for Alzheimer's disease. 2. Beta-Asarone prevents autophagy and synaptic loss by reducing ROCK expression in SAMP8 mice. 3. The co-administration of beta-Asarone(Cis-Isoasarone) and l-dopa may contribute to the treatment of 6-OHDA-induced damage in rats by inhibiting autophagy activity. 4. Beta-Asarone exhibits anti-inflammatory effects by suppressing the production of pro-inflammatory mediators through NF-κB signaling and the JNK pathways in activated microglial cells and might be developed as a promising candidate to treat various neuroinflammatory diseases.