Pain

Phorbol 12-myristate 13-acetate (PMA; TPA; Phorbol myristate acetate), a phorbol ester, is a dual SphK and protein kinase C (PKC) activator. Phorbol 12-myristate 13-acetate is a NF-κB activator. Phorbol 12-myristate 13-acetate induces differentiation in THP-1 cells (Validated by MedChemExpress).

Rapamycin (Sirolimus; AY 22989) is a potent and specific blood-brain barrier-transmissible mTOR inhibitor with an IC₅₀ of 0.1 nM in HEK293 cells. Rapamycin is a molecular glue that binds FKBP12 and mTOR proteins together, thereby inhibiting mTOR kinase activity. Rapamycin binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1. Rapamycin is an autophagy activator, an immunosuppressant.

Chloroquine is an antimalarial and anti-inflammatory agent widely used to treat malaria and rheumatoid arthritis. Chloroquine is an autophagy and toll-like receptors (TLRs) inhibitor. Chloroquine is highly effective in the control of SARS-CoV-2 (COVID-19) infection in vitro (EC₅₀=1.13 μM).

Dexamethasone (Hexadecadrol) is a glucocorticoid receptor agonist, apoptosis inducer, and common disease inducer in experimental animals, constructing models of muscle atrophy, hypertension, and depression. Dexamethasone can inhibit the production of inflammatory miRNA-155 exosomes in macrophages and significantly reduce the expression of inflammatory factors in neutrophils and monocytes. Dexamethasone also has potential for use in COVID-19 research.

Lipopolysaccharides, from E. coli O55:B5 (LPS, from Escherichia coli (O55:B5)) are endotoxins and TLR4 activators extracted from Escherichia coli (E. coli O55:B5) and are classified as S (smooth) type LPS. Lipopolysaccharides, from E. coli O55:B5 possess the typical three-part structure: O-antigen, core oligosaccharide, and lipid A. Lipopolysaccharides, from E. coli O55:B5 activate TLR-4 in immune cells, exhibit high pyrogenicity, and demonstrate dose and serotype specificity. Lipopolysaccharides, from E. coli O55:B5 can be widely used to induce cellular inflammation and establish animal models related to inflammation.
It is recommended to prepare a solution with concentration ≥2 mg/mL. Vortex thoroughly for more than 10 minutes. Due to the adsorption characteristics of LPS, silanized container or low adsorption centrifuge tubes should be used for aliquoting and storage, and mix thoroughly before use.

YHV98-4 is a selective, blood-brain barrier permeable Hv1 channel inhibitor. YHV98-4 specifically inhibits Hv1 with a half-maximal inhibitory concentration of 1 µM without inhibiting other ion channels. YHV98-4 reduces the propagation of p-tau. YHV98-4 increases ATP production, and enhances microglial mitophagy. YHV98-4 attenuates inflammatory pain via inhibition of Hv1 and ROS production. YHV98-4 enhances microglia-to-neuron mitochondrial transfer, promoting the delivery of functional mitochondria to rescue neuronal damage and improve cognitive function. YHV98-4 reduces inflammation. YHV98-4 can be used in the research of Alzheimer's disease.

Agmatine is an orally active analgesic that can cross the blood-brain barrier. Agmatine targets the 5-HT_2A receptor, 5-HT₃ receptor, α₂-adrenergic receptor, and I1 imidazoline receptor. Agmatine produces dose-dependent analgesic effects in various pain models. Agmatine can be used in research related to visceral pain, neuropathic pain, and inflammatory pain.

PSB-10211 is a P2X2 receptor antagonist with an IC₅₀ of 0.086 μM against rat P2X2 receptors. PSB-10211 inhibits ATP-mediated currents of rat P2X2 receptors expressed in Xenopus oocytes. PSB-10211 can be used in studies related to pain and urinary incontinence.

Staurosporine is a potent, ATP-competitive and non-selective inhibitor of protein kinases with IC₅₀s of 6 nM, 15 nM, 2 nM, and 3 nM for PKC, PKA, c-Fgr, and Phosphorylase kinase respectively. Staurosporine also inhibits TAOK2 with an IC₅₀ of 3 μM. Staurosporine is an apoptosis inducer.

LY294002 is a broad-spectrum inhibitor of PI3K with IC₅₀s of 0.5, 0.57, and 0.97 μM for PI3Kα, PI3Kδ and PI3Kβ, respectively. LY294002 also inhibits CK2 with an IC₅₀ of 98 nM. LY294002 is a competitive DNA-PK inhibitor that binds reversibly to the kinase domain of DNA-PK with an IC₅₀ of 1.4 μM. LY294002 is an apoptosis activator.

Bortezomib (PS-341) is a reversible and selective proteasome inhibitor, and potently inhibits 20S proteasome (K_i=0.6 nM) by targeting a threonine residue. Bortezomib disrupts the cell cycle, induces apoptosis, and inhibits NF-κB. Bortezomib is the first proteasome inhibitor anticancer agent. Bortezomib can be used for the study of multiple myeloma (MM). Bortezomib effectively inhibits TREM2 expression in tumor-associated macrophages (TAMs).

Metformin (1,1-Dimethylbiguanide) inhibits the mitochondrial respiratory chain in the liver, leading to AMPK activation and enhancing insulin sensitivity, and can be used in the study of type 2 diabetes. Metformin exerts central glucose-lowering effects by inhibiting Ras-related protein 1 (Rap1) in SF1 hypothalamic neurons. Metformin also inhibits liver oxidative stress, nitrosative stress, inflammation, and apoptosis caused by liver ischemia/reperfusion injury. In addition, Metformin regulates the expression of autophagy-related proteins by activating AMPK and inhibiting the mTOR signaling pathway, thereby inducing tumor cell autophagy and inhibiting the growth of renal cell carcinoma in vitro and in vivo.

Trametinib (GSK1120212; JTP-74057) is an orally active MEK inhibitor that inhibits MEK1 and MEK2 with IC₅₀s of about 2 nM. Trametinib activates autophagy and induces apoptosis, cross the blood-brain barrier (BBB), used in research related to subarachnoid hemorrhage (SAH).

Ruxolitinib (INCB18424) is an orally active and selective JAK1/2 inhibitor with IC₅₀s of 3.3 nM and 2.8 nM in cell-free assays, and has 130-fold selectivity for JAK1/2 over JAK3. Ruxolitinib induces autophagy and kills tumor cells through toxic mitophagy.

Hydrocortisone (Cortisol) is a steroid hormone or glucocorticoid secreted by the adrenal cortex.

BAY 11-7082 is an IκBα phosphorylation and NF-κB inhibitor. BAY 11-7082 selectively and irreversibly inhibits the TNF-α-induced phosphorylation of IκB-α, and decreases NF-κB and expression of adhesion molecules. BAY 11-7082 inhibits ubiquitin-specific protease USP7 and USP21 (IC₅₀=0.19, 0.96 μM, respectively). BAY 11-7082 inhibits gasdermin D (GSDMD) pore formation in liposomes and inflammasome-mediated pyroptosis and IL-1β secretion in human and mouse cells.

Yoda 1 is a potent and selective Piezo1 agonist. Yoda 1 activates purified Piezo1 channels. Yoda 1 potently inhibits macropinocytosis induced by epidermal growth factor (EGF). Yoda 1 enhances Ca²⁺ influx followed by activation of the calcium-activated potassium channel KCa3.1 and inhibition of Rac1 activation.

Rosiglitazone (BRL 49653) is an orally active selective PPARγ agonist (EC₅₀: 60 nM, K_d: 40 nM), with blood-brain barrier permeability. Rosiglitazone is an TRPC5 activator (EC₅₀: 30 μM) and TRPM3 inhibitor. Rosiglitazone can be used in the research of obesity and diabetes, senescence, ovarian cancer.

Quercetin, a natural flavonoid, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC₅₀ of 2.4 μM, 3.0 μM and 5.4 μM for PI3K γ, PI3K δ and PI3K β, respectively.

Resiquimod is a Toll-like receptor 7 and 8 (TLR7/TLR8) agonist that induces the upregulation of cytokines such as TNF-α, IL-6 and IFN-α.