BChE Inhibitor

Imperatorin is an effective of NO synthesis inhibitor (IC₅₀=9.2 μmol), which also is a BChE inhibitor (IC₅₀=31.4 μmol). Imperatorin is a weak agonist of TRPV1 with EC₅₀ of 12.6±3.2 μM.

Garcinol, a polyisoprenylated benzophenone harvested from Garcinia indica, exerts anti-cholinesterase properties towards acetyl cholinesterase (AChE) and butyrylcholinesterase (BChE) with IC₅₀s of 0.66 μM and 7.39 μM, respectively. Garcinol also inhibits histone acetyltransferases (HATs, IC₅₀= 7 μM) and p300/CPB-associated factor (PCAF, IC₅₀ = 5 μM). Garcinol has anti-inflammatory and anti-cancer activity.

Rivastigmine (ENA 713 free base) is an orally active and potent cholinesterase (ChE) inhibitor and inhibits butyrylcholinesterase (BChE) and acetylcholinesteras (AChE) with IC₅₀s of 0.037 μM , 4.15 μM, respectively. Rivastigmine can pass the blood brain barrier (BBB). Rivastigmine is a parasympathomimetic or cholinergic agent used for the research of mild to moderate dementia of the Alzheimer's type and dementia due to Parkinson's disease.

Epiberberine chloride is an alkaloid isolated from Coptis chinensis, acts as a potent AChE and BChE inhibitor, and a non-competitive BACE1 inhibitor, with IC₅₀s of 1.07, 6.03 and 8.55 μM, respectively. Epiberberine chloride has antioxidant activity, with peroxynitrite ONOO^- scavenging effect (IC₅₀, 16.83 μM), and may protect against Alzheimer disease. Epiberberine chloride inhibits the early stage of differentiation of 3T3-L1 preadipocytes, downregulates the Raf/MEK1/2/ERK1/2 and AMPKα/Akt pathways. Epiberberine has the potential effect in the research of diabetic disease.

Tacrine hydrochloride is a potent brain-penetrant inhibitor of both AChE and BChE, with IC₅₀s of 31 nM and 25.6 nM, respectively. Tacrine hydrochloride is also a NMDAR inhibitor, with an IC₅₀ of 26 μM. Tacrine hydrochloride can be used for the research of Alzheimer’s disease.

COX-2-IN-67 is an orally active, blood-brain barrier permeable multi-target inhibitor that potently targets COX-2 (IC₅₀=0.07 μM), hCA IX (K_i=62.7 nM) and hBuChE (IC₅₀=0.47 μM). COX-2-IN-67 alleviates oxidative stress and liver stress, improves glucose homeostasis and insulin sensitivity, and optimizes lipid profiles. Meanwhile, COX-2-IN-67 effectively reduces the levels of neuroinflammatory markers and improves hippocampus-dependent cognitive function in a high-fat diet-induced rat model. COX-2-IN-67 can be used for the research of metabolic dysfunction-associated mild cognitive impairment.

BuChE-IN-22 is a pseudo-irreversible butyrylcholinesterase (BuChE) inhibitor, with IC₅₀ values of 4 nM and 157 nM against hBuChE and hAChE, respectively. It also acts as a prodrug of 7-hydroxysertraline. BuChE-IN-22 releases 7-hydroxysertraline during BuChE inhibition. BuChE-IN-22 completely reverses Aβ_25-35-induced short-term and long-term memory impairments in a mouse model of Alzheimer's disease. BuChE-IN-22 can be used in research related to Alzheimer's disease.

Ethopropazine (Isothazine) hydrochloride is a potent and selective BChE inhibitor, a poor AChE inhibitor and a non-selective mAChR and NMDA antagonist. Ethopropazine hydrochloride has anticholinergic, antihistamine, antiadrenergic actions and properties. Ethopropazine hydrochloride alleviates thermal hyperalgesia in a dose dependent manner. Ethopropazine hydrochloride can be used for the research of Parkinson’s disease.

Cornuside is an iridoid glycoside with anti-allergic, anti-inflammatory, and neuroprotective activities. Cornuside exerts anti-allergic activity by downregulating the p38 MAPK, JNK, and NF-κB signaling pathways, and inhibits IgE-mediated histamine release from mast cells. Cornuside improves cognitive impairment in mice by inhibiting BACE1 activity (IC₅₀ = 55.84 μg/mL) and enhancing ChAT activity. Cornuside inhibits LPS (HY-D1056)-induced inflammatory mediators, including iNOS, COX-2, PGE2, TNF-α, IL-6, and IL-1β, by suppressing NF-κB activation.

Aaptamine is an alkaloid that can be isolated from the sponge Aaptos suberitoides. Aaptamine is a competitive antagonist of the α-adrenergic receptor, as well as an inhibitor of the proteasome and cholinesterase. Aaptamine is cytotoxic to tumor cells and can induce apoptosis, cell cycle arrest of tumor cells, and the expression of p21 through a p53-independent pathway. Aaptamine has multiple activities such as anti-tumor, antioxidant, antibacterial, and analgesic effects.

Drofenine (Cycloadiphene; Hexahydroadiphenine) hydrochloride is an brain-penetrant antispasmodic agent. Drofenine hydrochloride is a Kv2.1 channel inhibitor with human IC₅₀ of 9.53 μM. Drofenine hydrochloride is a butyrylcholinesterase (BChE) inhibitor with K_i of 0.003 mM, and is a TRPV3 activator. Drofenine hydrochloride blocks Kv2.1-dependent potassium efflux, inhibits Kv2.1/JNK/NF-κB and IkBa/NF-kB signaling, suppresses Kv2.1 mRNA/protein expression. Drofenine suppresses oligomeric Aβ-induced microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation, improves cognitive impairment, promotes neurite outgrowth. Drofenine hydrochloride induces calcium influx in keratinocytes and exert cytotoxicity against keratinocytes. Drofenine hydrochloride ameliorates diabetic peripheral neuropathy -like pathology. Drofenine hydrochloride can be used for the researches of Alzheimer's disease, diabetic peripheral neuropathy and smooth muscle spasm.

ACG548B (compound 24) is a potent inhibitor of acetyl- and butyrylcholinesterase (AChE and BChE) with IC₅₀s of 1.78 and 0.496 μM, respectively. ACG548B has higher AChE affinity and selectivity over BChE and ChoK (choline kinase). ACG548B can be uesd for the study of myasthenia gravis and neuromuscular blockade.

p-Xylene bis(pyridinium bromide) (compound 21), a cationic charged quencher, is a week bisquaternary AChE and BChE inhibitor with IC₅₀s of 1540 μM and 529 μM, respectively.

Pteryxin ((+)-Pteryxin) is an orally active multi-target inhibitor that targets NF-κB, MAPK, NLRP3 inflammasome, and Nrf2/ARE pathways. Pteryxin is also a BChE inhibitor (IC₅₀=12.96 μg/mL) with a low inhibitory efficiency on AChE. Pteryxin inhibits the Ca²⁺-calcineurin-NFATc1 pathway by blocking NF-κB/MAPK signaling, inhibiting NLRP3 inflammasome activation, and reducing ROS generation, and activates Nrf2-mediated antioxidant enzyme expression. Pteryxin has anti-inflammatory, antioxidant, and osteoclastogenesis inhibitory activities. Pteryxin can be used in the study of inflammatory diseases, osteoporosis, diabetes, and Alzheimer's disease.

Ambenonium (WIN 8077) chloride is an orally active and reversible inhibitor of Acetyicholinesterase (AChE) with high affinity. Ambenonium chloride inhibits human AChE with an IC₅₀ value of 0.7 nM (hAChE).

N-Nornuciferine is an orally active, blood-brain barrier-permeable CYP2D6 inhibitor, with an IC₅₀ of 3.76 μM and a K_i of 2.34 μM against human CYP2D6. N-Nornuciferine also acts as a BChE inhibitor, showing an IC₅₀ of 5.6 μM in mice. N-Nornuciferine can be used in the research of neurological-related diseases.

Gypsogenin is a selective mixed-type BChE inhibitor (K_i=19.99 μM) that also exhibits significant cytotoxicity against various human cancer cell lines. Gypsogenin inhibits tumor growth by inducing cell cycle arrest and triggering apoptosis. Gypsogenin displays antibacterial activity against bacteria such as Bacillus subtilis and Bacillus thuringiensis, and often serves as a key parent nucleus for the synthesis of anticancer compounds. Gypsogenin is widely used in research on Alzheimer's disease and various cancers including colon cancer, melanoma, and leukemia.

Tacrine hydrochloride (hydrate) is an inhibitor of both acetyl (AChE) and butyryl-cholinestrase (BChE) with IC₅₀s of 31 nM and 25.6 nM, respectively.

Methylene Violet 3RAX is a phenazine dye to stain the mitochondria of cells. Methylene Violet 3RAX can change the molecular structure of DNA, undermine the module of DNA, and induce the generation of the reactive singlet oxygen. Methylene Violet 3RAX shows inhibition for human erythrocyte AChE and human plasma BChE with an K_is of 1.58, 0.51 μM, respectively. Methylene Violet 3RAX has the potential for the research of potential photosensitizers for mitochondrial targeting action in PDT (photodynamic therapy).

Ebeiedinone, a steroidal alkaloid from Fritillaria species, inhibits the bioactivity of human whole blood cholinesterase (ChE) at the concentration of 0.1 mM, with the inhibitory effects of 69.0%.