Neurological Disease

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.

Tamoxifen (ICI 47699) is an orally active, selective estrogen receptor modulator (SERM) which blocks estrogen action in breast cells and can activate estrogen activity in other cells, such as bone, liver, and uterine cells. Tamoxifen is a potent Hsp90 activator and enhances the Hsp90 molecular chaperone ATPase activity. Tamoxifen also potent inhibits infectious EBOV Zaire and Marburg (MARV) with IC₅₀ of 0.1 μM and 1.8 μM, respectively. Tamoxifen activates autophagy and induces apoptosis. Tamoxifen can also be dissolved in corn oil (HY-Y1888) for use in inducing gene knockout in CreER transgenic mice. Tamoxifen has better solubility in corn oil compared to Tamoxifen Citrate (HY-13757).

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.

Acetylcysteine (N-Acetylcysteine) is a mucolytic agent that can cross the blood-brain barrier, which reduces the thickness of the mucus. Acetylcysteine is a ROS inhibitor. Acetylcysteine is a cysteine precursor, prevents hemin-induced ferroptosis by neutralizing toxic lipids generated by arachidonate-dependent activity of 5-lipoxygenases. Acetylcysteine induces cell apoptosis. Acetylcysteine also has anti-influenza virus activities. In addition, Acetylcysteine ​​is the most stable form of cysteine ​​during drug delivery and can be used in disulfidptosis studies.

Y-27632 dihydrochloride is an orally active and ATP-competitive ROCK (Rho-kinase) inhibitor (ROCK-I K_i=220 nM; ROCK-II K_i=300 nM). Y-27632 dihydrochloride shows antiepileptic effects.

Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC₅₀s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with K_d of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha.

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.

Palmitic acid is a long-chain saturated fatty acid commonly found in both animals and plants. PA can induce the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in in mouse granulosa cells. Palmitic acid is used to establish a cell steatosis model.

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).

Semaglutide is a long-acting, selective, competitive GLP-1R agonist that can penetrate the blood-brain barrier. After activating GLP-1R, Semaglutide promotes insulin secretion, inhibits gastric emptying and appetite, and at the same time enhances autophagy, inhibits oxidative stress and apoptosis. Semaglutide also regulates mitochondrial function and lipid metabolism (such as reducing de novo lipogenesis in the liver). Semaglutide has activities such as lowering blood sugar, reducing weight, neuroprotection (such as improving motor function in Parkinson's disease models, reducing α-synuclein aggregation) and improving hepatic steatosis. Semaglutide can be used for the study of neurodegenerative diseases and liver diseases such as type 2 diabetes, obesity, Parkinson's disease, metabolic associated fatty liver disease (MASLD), and cancer.

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

DAPT (GSI-IX) is a potent and orally active γ-secretase inhibitor with IC₅₀s of 115 nM and 200 nM for total amyloid-β (Aβ) and Aβ₄₂, respectively. DAPT inhibits the activation of Notch 1 signaling and induces cell differentiation. DAPT also induces autophagy and apoptosis. DAPT has neuroprotection activity and has the potential for autoimmune and lymphoproliferative diseases, degenerative disease and cancers treatment.

Cyclosporin A (Cyclosporine A) is an immunosuppressant which binds to the cyclophilin and inhibits phosphatase activity of protein phosphatase 2B (PP2B/calcineurin) with an IC₅₀ of 5 nM. Cyclosporin A is a molecular glue, binds to cyclophilin and calcineurin, leading to inactivation of nuclear Factor of activated T Cells (NFAT) and a subsequent decrease in the immune response. Cyclosporin A also inhibits CD11a/CD18 adhesion.

Rotenone is a mitochondrial electron transport chain complex I inhibitor. Rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production.

Estradiol (β-Estradiol) is a steroid hormone and the major female sex hormone. Estradiol can up-regulate the expression of neural markers of human endometrial stem cells (hEnSCs) and promote their neural differentiation. Estradiol can be used for the research of cancers, neurodegenerative diseases and neural tissue engineering.

L-Ascorbic acid (L-Ascorbate), an electron donor, is an endogenous antioxidant agent. L-Ascorbic acid inhibits selectively Ca_v3.2 channels with an IC₅₀ of 6.5 μM. L-Ascorbic acid is also a collagen deposition enhancer and an elastogenesis inhibitor. L-Ascorbic acid exhibits anti-cancer effects through the generation of reactive oxygen species (ROS) and selective damage to cancer cells.

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.

Sorafenib (Bay 43-9006) is a potent oral active multikinase inhibitor. Sorafenib blocks autophosphorylation and activity of receptor tyrosine kinases (VEGFR-2, VEGFR-3) and RAF family kinases, thereby suppressing the RAF/MEK/ERK and PI3K/Akt pathways, inhibiting STAT3 phosphorylation, and selectively inhibiting the MAPK pathway in cancer cells. Sorafenib induces cell cycle arrest, autophagy, apoptosis, and PARP cleavage, reduces Bcl-2, Bcl-XL, cyclin D1 levels, and activates Bak and Bax. Sorafenib inhibits tumor growth and metastasis in mouse and rat models. Sorafenib can be used for cancer research, such as colon, breast, non-small-cell lung cancer (NSCLC), ovarian, pancreatic, melanoma, colorectal and hepatocellular carcinoma.

Dasatinib (BMS-354825) is a highly potent, ATP competitive, orally active dual Src/Bcr-Abl inhibitor with potent antitumor activity. The K_is are 16 pM and 30 pM for Src and Bcr-Abl, respectively. Dasatinib inhibits Bcr-Abl and Src with IC₅₀s of <1.0 nM and 0.5 nM, respectively. Dasatinib also induces apoptosis and autophagy, and can cross the blood-brain barrier.