Cholinesterase (ChE) Modulator

Trimyristin is an orally active compound. Trimyristin can be isolated from the seeds of nutmeg (Myristica fragrans). Trimyristin inhibits the activities of acetylcholinesterase (AChE), ACP and ALP, with IC₅₀ values of 0.11, 0.16 and 0.18 mM, respectively. Trimyristin exerts competitive-noncompetitive inhibition on acetylcholinesterase, uncompetitive inhibition on ACP, and competitive/noncompetitive inhibition on ALP. Trimyristin restores the downregulated acetylcholinesterase concentration in the cerebral cortex of rats exposed to sodium arsenite. Trimyristin can be used in studies related to fascioliasis and neurotoxicity.

Polygalic acid is a polyphenolic acid with neuroprotective effects, and also an inhibitor of African swine fever virus polymerase (AsfvPolX), with an IC₅₀ value of 5.05 μM. Polygalic acid alleviates neuroinflammation by regulating cholinergic activity, and its fecal level decreases in diseased mice. Polygalic acid can be used in research related to painful diabetic peripheral neuropathy complicated with cognitive impairment and African swine fever.

Glycyl-L-glutamic acid is a neurotrophic factor (NF) in vivo, and exerts function of maintenance of AChE content and activity. Glycyl-L-glutamic acid doesn’t act directly on AChE synthesis, and may prevent preganglionic neuronal degeneration.

Bacoside A is an orally active, blood-brain barrier-permeable triterpenoid saponin that modulates the activities of ATPases, AChE, CaMK2A and iNOS. Derived from Bacopa monniera. Bacoside A exerts significant antioxidant, anti-inflammatory and anti-apoptotic effects by maintaining ion balance, scavenging reactive oxygen species, stabilizing cell membranes, and regulating the expression of NF-κB and apoptosis-related proteins. Bacoside A counteracts morphine-induced reductions in Na⁺/K⁺-ATPase, Ca²⁺-ATPase and Mg²⁺-ATPase activities, increases mitochondrial membrane potential, and decreases intracellular reactive oxygen species levels. Bacoside A specifically binds to calcium/calmodulin-dependent protein kinase IIA to trigger endoplasmic reticulum calcium release. Bacoside A exhibits non-apoptotic cytotoxicity against glioblastoma cells while protecting normal nerve cells from stress-induced damage. Bacoside A is applicable to the research of Parkinson's disease and glioblastoma multiforme.

AChE-IN-74 (Compound 10) is a modulator for cholinesterase. AChE-IN-74 inhibits the proliferation of liver cancer cell Hep3B and SkHep1 with IC₅₀ of 3.6 and 19.9 μM. AChE-IN-74 exhibits a low embryonic toxicity in zebrafish models (10-15 μM).

EQ-04 is a highly selective positive allosteric modulator (PAM) of α7 nAChR. EQ-04 has no direct inhibitory activity on AChE and BChE. EQ-04 inhibits Aβ aggregation. EQ-04 has safe cytotoxicity and potent neuroprotective activity. EQ-04 can be used for the study of Alzheimer's disease.

JNJ-1930942 is a selective and blood-brain barrier (BBB) penetrant α(7) nAChR positive allosteric modulator.JNJ-1930942 enhances the Choline (HY-B0282)-evoked rise in intracellular Ca²⁺ levels and neurotransmission at hippocampal dentate gyrus synapses. JNJ-1930942 reverses the naturally occurring sensory gating deficit in DBA/2 mice.

VU0366369 (ML137) is a selective positive allosteric modulator (PAM) for mAChR M1 with an EC₅₀ of 830 nM. VU0366369 can be used in research about central nervous system diseases.