Neurological Disease

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.

Doxycycline, an antibiotic, is an orally active and broad-spectrum metalloproteinase (MMP) inhibitor. Doxycycline shows antibacterial activity and anti-cancer cell proliferation activity.

Cholesterol (from animal) is the major sterol in mammals. It is making up 20-25% of structural component of the plasma membrane. Plasma membranes are highly permeable to water but relatively impermeable to ions and protons. Cholesterol (from animal) plays an important role in determining the fluidity and permeability characteristics of the membrane as well as the function of both the transporters and signaling proteins. Cholesterol (from animal) is also an endogenous estrogen-related receptor α (ERRα) agonist.

Deferoxamine mesylate (Deferoxamine B mesylate) is an iron chelator (binds to Fe(III) and many other metal cations), is widely used to reduce iron accumulation and deposition in tissues. Deferoxamine mesylate upregulates HIF-1α levels with good antioxidant activity. Deferoxamine mesylate also shows anti-proliferative activity, can induce apoptosis and autophagy in cancer cells. Deferoxamine mesylate can be used in studies of diabetes, neurodegenerative diseases as well as anti-cancer and anti-COVID-19.

Mito-TEMPO is a mitochondria-targeted antioxidant. Mito-TEMPO induces mitophagy by activating the PINK1/Parkin pathway, inhibits NLRP3 inflammasome activation, restores mitochondrial membrane potential, and improves renal function and podocyte injury. Mito-TEMPO regulates Ca²⁺ homeostasis, inhibits Bnip3 overexpression, shortens action potential duration, and exerts antiarrhythmic effects. Mito-TEMPO reverses premature senescence, reduces trabecular bone loss, and decreases cell apoptosis. Mito-TEMPO can be used in studies of chronic kidney disease, age-related cardiac dysfunction, postmenopausal osteoporosis, and ischemic stroke.

Bucladesine (Dibutyryl cAMP; DBcAMP) sodium is a membrane-permeable 3′, 5′-cyclic adenosine monophosphate (cAMP) analog. Bucladesine selectively activates cAMP dependent protein kinase (PKA) by increasing the intracellular level of cAMP. Bucladesine significantly attenuates MDMA-induced increases in hippocampal mitochondrial ROS formation, mitochondrial outer membrane damage, cytochrome c release, and hippocampal ADP/ATP ratio, thereby improving spatial learning and memory impairments. Bucladesine exhibit anti-nociceptive and anti-inflammation effect. Bucladesine can inhibit cancer cells proliferation, induce apoptosis. Bucladesine can be used for the researches of neurological disease, cancer, inflammation.

Resatorvid (TAK-242) is a selective Toll-like receptor 4 (TLR4) inhibitor. Resatorvid inhibits NO, TNF-α and IL-6 production with IC_50s of 1.8 nM, 1.9 nM and 1.3 nM, respectively. Resatorvid downregulates expression of TLR4 downstream signaling molecules MyD88 and TRIF. Resatorvid inhibits autophagy and plays pivotal role in various inflammatory diseases.

Clozapine N-oxide is a major metabolite of Clozapine and a human muscarinic designer receptors (DREADDs) agonist. Clozapine N-oxide activates the DREADD receptor hM3Dq and hM4Di. Clozapine N-oxide can't cross the blood-brain barrier. Clozapine is a potent dopamine antagonist and also a potent and selective muscarinic M4 receptor (EC₅₀=11 nM) agonist.

D-Galactose is a natural aldohexose and C-4 epimer of glucose.

Resveratrol (trans-Resveratrol; SRT501) is a CNS-penetrant natural polyphenolic phytoalexin that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties. Resveratrol (SRT 501) has a wide spectrum of targets including mTOR, JAK, β-amyloid, Adenylyl cyclase, IKKβ, DNA polymerase. Resveratrol also is a specific SIRT1 activator. Resveratrol is a potent pregnane X receptor (PXR) inhibitor. Resveratrol is an Nrf2 activator, ameliorates aging-related progressive renal injury in mice model. Resveratrol increases production of NO in endothelial cells.

MPTP hydrochloride is a brain penetrant dopaminergic neurotoxin. MPTP hydrochloride can be used to induce Parkinson’s Disease model. MPTP hydrochloride, a precusor of MPP⁺, induces apoptosis. MPTP hydrochloride has been verified by MCE with professional biological experiments.

SB 202190 is a selective p38 MAP kinase inhibitor with IC₅₀s of 50 nM and 100 nM for p38α and p38β2, respectively. SB 202190 binds to the ATP pocket of the active recombinant human p38 kinase with a K_d of 38 nM. SB 202190 has anti-cancer activity and rescued memory deficits. SB202190 induces autophagy.

(+)-JQ-1 (JQ1), a chemical probe, is a potent, specific, CNS-penetrant and reversible BET bromodomain inhibitor, with IC₅₀s of 77 and 33 nM for the first and second bromodomain (BRD4(1/2)). (+)-JQ-1 also activates autophagy.

SC79, a unique specific and BBB permeable Akt activator, activates Akt in the cytosol and inhibits Akt membrane translocation. SC79 specifically binds to the PH domain of Akt.

Chlorpromazine is an orally active, blood-brain barrier-transparent antipsychotic agent that effectively antagonises D2 dopamine receptors and 5-HT_2A, which is widely used in schizophrenia and other psychiatric disorders. Chlorpromazine exerts anti-cancer activity through a variety of pathways, including anti-proliferation, induction of autophagy and cycle arrest (G2-M phase), inhibition of cytochrome c oxidase (CcO), inhibition of tumour growth and metastasis, and inhibition of tumour immune escape. Chlorpromazine also blocks hNa_v1.7 channels (IC₅₀=25.9 μM; concentration-dependent) and HERG potassium channels (IC₅₀=21.6 μM), which has potential for analgesic and cardiac arrhythmic studies. Chlorpromazine also can inhibit clathrin-mediated endocytosis.

Corticosterone (17-Deoxycortisol) is an orally active and adrenal cortex-produced glucocorticoid, which plays an important role in regulating neuronal functions of the limbic system (including hippocampus, prefrontal cortex, and amygdala). Corticosterone increases the Rab-mediated AMPAR membrane traffic via SGK-induced phosphorylation of GDI. Corticosterone also interferes with the maturation of dendritic cells and shows a good immunosuppressive effect.

Tofacitinib (Tasocitinib) is an orally active, blood-brain barrier permeable selective inhibitor of JAK1/JAK3. Tofacitinib blocks the JAK-STAT/NF-κB signaling pathway, inhibits cytokine signal transduction, phosphorylation of STAT1/STAT5, and suppresses innate and adaptive immune responses. Tofacitinib can be used in research related to major depressive disorder, rheumatoid arthritis, pulmonary diseases, systemic lupus erythematosus, and immune-mediated liver injury.

Everolimus (RAD001) is a Rapamycin (HY-10219) derivative and a potent, selective, orally active, blood-brain barrier-permeable mTOR1 inhibitor. Everolimus binds to FKBP-12 to generate an immunosuppressive complex. Everolimus inhibits tumor cells proliferation and induces cell apoptosis and autophagy. Everolimus has potent immunosuppressive and anticancer activities.

Capsaicin ((E)-Capsaicin), an active component of chili peppers, is a TRPV1 agonist. Capsaicin induces a nociceptive response by binding to its receptors. Capsaicin has analgesic effects on neurological disorders. Capsaicin has antioxidant, anti-inflammatory, anti-cancer effects.

Doxycycline hyclate, an antibiotic, is an orally active and broad-spectrum metalloproteinase (MMP) inhibitor. Doxycycline hyclate shows antibacterial activity and anti-cancer cell proliferation activity. Doxycycline hyclate can be used to construct gene expression regulation models.