MPP+ iodide, the metabolite of a neurotoxin MPTP, causes symptom of Parkinson's disease (PD) in animal models by selectively destroying dopaminergic neurons in substantia nigra. MPP+ induces dopamine transporter (DAT) externalization in dopaminergic (DA)

Specnuezhenide (Nuezhenide) significantly protects human neuroblastoma SH-SY5Y cells from 6-hydroxydopamine-induced neurotoxicity.Nuezhenide is the main inhibitory compound of fruits, it shows a clear inhibitory effect to the seeds of wheat and Chinese cabbage.

Chrysotoxine (Phenol, 4-[2-(3,4-dimethoxyphenyl)ethyl]-2,6-dimethoxy-) inhibits 6-hydroxydopamine induced apoptosis in SH-SY5Y cells via NF-κB modulation and mitochondria protection.

Biatractylolide has a neuroprotective effect on glutamate-induced injury in PC12 and SH-SY5Y cells through a mechanism of the PI3K-Akt-GSK3β-dependent pathways. The molecular mechanisms of inhibitory activities of biatractylolide on AChE are not only thro

MAO-B-IN-26 (Compound IC9) serves as both a MAO-B and acetylcholinesterase inhibitor. It safeguards SH?SY5Y cells from Aβ-induced toxicity, including morphological alterations, reactive oxygen species (ROS) production, and membrane damage, while also preventing Aβ-triggered autophagy and apoptosis. As such, MAO-B-IN-26 holds potential as a neuroprotective agent in the context of Alzheimer’s disease [1].

Marcfortine A is an indole alkaloid originally isolated from P. roqueforti. It has nematocidal activity against the parasitic nematode H. contortus (LD99 = 0.06 μg/ml) and inhibits motility of adult worms (EC50 = 2 μM)., Marcfortine A eliminates H. contortus, T. colubriformis, and O. ostertagi from experimentally infected jirds (ED95s = 0.33, 0.11, and 2.5 mg/animal, respectively). It dose-dependently inhibits nicotine-induced calcium mobilization in SH-SY5Y and TE-671 cells expressing α3 subunit-containing human nicotinic acetylcholine receptors (nAChRs) and muscle-type nAChRs, respectively.

Kobophenol A has antimicrobial, and anti-inflammatory activities, it might be a candidate for treatment of inflammatory bone diseases relevant to osteoblast cell death. Kobophenol A inhibits AChE activity in a dose-dependent manner, and the IC50 value is

Kaempferol-3,7-di-O-β-glucoside (Kaempferol 3,7-diglucoside) is a flavonol from Morettia philaena, It can inhibit α-amylase, α-glucosidase and Acetylcholinesterase. Kaempferol-3, 7-di-o-β-Glucoside has neuroprotective activity and can slow down differentiated neuronal cells SH-SY5Y from Amyloid β peptide-induced damage. Kaempferol-3, 7-di-o-β-Glucoside can be used to study neurological disorders like Alzheimer's disease.

Cearoin has anti-inflammatory, and antiallergic activities, it can markedly inhibit inflammatory responses including LPS-induced NO production by suppressing the expression of iNOS mRNA and LPS-induced mRNA expression of TNFα and CCL2. Cearoin induces aut

Mirodenafil dihydrochloride is a PDE-5 inhibitor developed for the treatment of erectile dysfunction.

YM-244769 dihydrochloride is an effective inhibitor of Na+/Ca2+ exchange 3 (NCX3) with an IC50 of 18 nM. YM-244769 dihydrochloride has efficient protective effects on neurons and kidneys.

ZDWX-25 is a highly potent dual inhibitor of GSK-3β and DYRK1A that possesses significant cytotoxic activities towards SH-SY5Y and HL-7702 cells. ZDWX-25 can be used for Alzheimer's disease research with an IC 50 value of 71 nM for GSK-3β [1].

Pituitary adenylate cyclase-activating peptide (PACAP) (6-27) is a PACAP receptor antagonist with IC50 values of 1,500, 600, and 300 nM, respectively, for rat PAC1, rat VPAC1, and human VPAC2 recombinant receptors expressed in CHO cells. It binds to PACAP receptors on SH-SY5Y and SK-N-MC human neuroblastoma and T47D human breast cancer cells (IC50s = 24.5, 106, and 105 nM, respectively) and inhibits cAMP accumulation induced by PACAP (1-38) (Kis = 457, 102, and 283 nM, respectively, in SH-SY5Y, SK-N-MC, and T47D cells). In vivo, in newborn pigs, PACAP (6-27) (10 μM) inhibits vasodilation of pial arterioles induced by PACAP (1-27) and PACAP (1-38) . It also inhibits PACAP (1-27)-stimulated increases in plasma insulin and glucagon levels and pancreatic venous blood flow in dogs when administered locally to the pancreas at a dose of 500 μg.

Orexin A (Hypocretin-1) (human, rat, mouse) acetate, a hypothalamic neuropeptide with analgesic abilities that penetrates the blood-brain barrier, acts as an OX1R agonist. It promotes the expression of BDNF and TH proteins within SH-SY5Y cells, showing both time- and dose-dependent responses. This compound is valuable for researching appetite control, neurodegenerative conditions, and the modulation of detrimental signaling [1] [2] [3].

Mirodenafil is a PDE-5 inhibitor developed for the treatment of erectile dysfunction.

Oxidopamine hydrochloride (6-Hydroxydopamine hydrochloride) is an neurotransmitter dopamine antagonist.

Anti-Aβ agent 1A is a potent anti-amyloid-β agent. Anti-Aβ agent 1A significantly inhibits LPS-induced IL-1β, IL-6 and TNF-α levels and reduces H2O2-induced apoptosis in SH-SY5Y cells using the mitochondrial pathway, exhibiting antioxidant, anti-inflammatory, anti-Aβ toxicity and neuroprotective activities. Anti-Aβ agent 1A can be used to study Alzheimer's disease.

Apostatin-1 (Apt-1) is a novel TRADD inhibitor. Apostatin-1 can bind to a pocket on the N-terminal TRAF2 binding domain of TRADD.

CBR-470-1 is a potent inhibitor of glycolytic phosphoglycerate kinase 1 (PGK1) that activates NRF2 by increasing methylglyoxal levels. CBR-470-1 is a non-covalent Nrf2 activator with neuroprotective activity that protects SH-SY5Y neuronal cells from MPP+-induced cytotoxicity by activating the Keap1-Nrf2 cascade. cytotoxicity induced by MPP+.

SB 242084 hydrochloride is a 5-HT2C receptor antagonist(pKi=9.0) that displays 158- and 100-fold selectivity over 5-HT2A and 5-HT2B receptors respectively.IC50 value: 9.0(pKi) [1]Target: 5-HT2C antagonistin vitro: SB 242084 had over 100-fold selectivity over a range of other 5-HT, dopamine and adrenergic receptors. In studies of 5-HT-stimulated phosphatidylinositol hydrolysis using SH-SY5Y cells stably expressing the cloned human 5-HT2C receptor, SB 242084 acted as an antagonist with a pKb of 9.3, which closely resembled its corresponding receptor binding affinity [1].in vivo: SB 242084 potently inhibited m-chlorophenylpiperazine (mCPP, 7 mgkg i.p. 20 min pre-test)-induced hypolocomotion in rats, a model of in vivo central 5-HT2C receptor function, with an ID50 of 0.11 mg/kg i.p., and 2.0 mg/kg p.o. SB 242084 (0.1-1 mg/kg i.p.) exhibited an anxiolytic-like profile in the rat social interaction test, increasing time spent in social interaction, but having no effect on locomotion. SB 242084 (0.1-1 mg/kg i.p.) also markedly increased punished responding in a rat Geller-Seifter conflict test of anxiety, but had no consistent effect on unpunished responding [1].

HUP-55 is a prolyl endopeptidase inhibitor with an IC50 of 5 nM, shown to mitigate α-synuclein dimerization in Neuro2a cells, stimulate autophagy in HEK293 cells, and lower hydrogen peroxide-evoked reactive oxygen species (ROS) production in SH-SY5Y cells at a 10 µM concentration. Additionally, administration of HUP-55 at a dosage of 10 mg/kg reduces ipsilateral paw use and diminishes striatal oligomeric α-synuclein concentrations in a Parkinson’s disease mouse model, which is induced through adenoviral vector-mediated overexpression of α-synuclein (AAV-αSyn).

SNJ-1945 is a calpain inhibitor with more favorable retinal penetration, high oral bioavailability, and long half-life. SNJ1945 rescued defective function in lissencephaly. SNJ-1945 protects SH-SY5Y cells against MPP(+) and rotenone. SNJ-1945 reduces murine retinal cell death in vitro and in vivo. SNJ-1945 has good aqueous solubility, can prevents the heart from KCl arrest-reperfusion injury associated with the impairment of total Ca(2+) handling by inhibiting the proteolysis of alpha-fodrin as a cardioplegia.

MTP 131 is a mitochondria-targeted peptide antioxidant.1,2It localizes to the mitochondria and reducestert-butyl hydroperoxide-induced lipid peroxidation and apoptosis in SH-SY5Y cells when used at concentrations ranging from 0.001 to 1 nM.1MTP 131 (2 mg/kg) reduces infarct volume, hemispheric swelling, and glutathione (GSH) depletion in a mouse model of acute cerebral ischemia induced by middle cerebral artery occlusion (MCAO).2It increases survival, improves motor function, and decreases degeneration of the lumbar spinal cord in a superoxide dismutase 1 mutant (SOD1G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS) when administered at a dose of 5 mg/kg. MTP 131 reduces albuminuria, urinary hydrogen peroxide levels, and mesangial matrix accumulation, as well as preserves superoxide production, in adb/dbmouse model of diabetic nephropathy.3 1.Zhao, K., Luo, G., Giannelli, S., et al.Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell linesBiochem. Pharmacol.70(12)1796-1806(2005) 2.Szeto, H.H.Mitochondria-targeted peptide antioxidants: Novel neuroprotective agentsAAPS J.8(3)E521-E531(2006) 3.Miyamoto, S., Zhang, G., Hall, D., et al.Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db/db mice against progression of diabetic kidney diseaseJ. Biol. Chem.295(21)7249-7260(2020)

High affinity and subtype selective α6β2 and α4β2 partial agonist (Ki values are 12 and 26nM for rat α6β2 and α4β2 receptors respectively). Has low affinity for α3β4 and α7 receptors (Ki values are 4.8 and 13 μM for human α3β4 and rat α7 receptors respectively). Stimulates dopamine release from striatal slices in vitro. Attenuates nicotine-induced self-administration and conditional place preference in rats. Sala et al (2013) CC4, a dimer of cytisine, is a selective partial agonist at α4β2/α6β2 nAChR with improved selectivity for tobacco smoking c Br.J.Pharmacol. 168 835 PMID:22957729 |Riganti et al (2005) Long-term exposure to the new nicotinic antagonist 1,2-bisN-cytisinylethane upregulates nicotinic receptor subtypes of SH-SY5Y human neuroblastoma cells. Br.J.Pharmacol. 146 1096 PMID:16273122 |Carbonnelle et al (2003) Nitrogen substitution modifies the activity of cytisine on neuronal nicotinic receptor subtypes. Eur.J.Pharmacol. 471 85 PMID:12818695

3,5-O-Dicaffeoylquinic acid (Isochlorogenic Acid A) is an isolated compound from Artemisia argyi; its ester derivatives exert anti-leucyl-tRNA synthetase of Giardia lamblia (GlLeuRS) and potential anti-giardial effects. 3,5-O-Dicaffeoylquinic acid (Isochlorogenic Acid A) as a neuraminidase inhibitory ligand in Flos Lonicerae, it has neuroprotective effects on SH-SY5Y cells and senescence-accelerated-prone mice 8 through the up-regulation of phosphoglycerate kinase-1. 3,5-O-Dicaffeoylquinic acid (Isochlorogenic Acid A) also has antioxidant and anti-complementary activities.

AZ-4217 is a high potency BACE inhibitor. It displays acute central efficacy in different in vivo models and reduced amyloid deposition in Tg2576 mice. AZ-4217 has IC50 160 pM in human SH-SY5Y cells with an excellent in vivo efficacy.

BIPM is a potent inhibitor of Rho-associated protein kinase 2 (ROCK2). Exposure of SH-SY5Y cells to BIPM led to significant changes in cell migration, actin stress fibers and neurite length. BIPM significantly inhibits phosphorylation of cofilin, a regula

CAY10410 is an analog of prostaglandin D2/prostaglandin J2 (PGD2/PGJ2) with structural modifications intended to give it PPARγ ligand activity and resistance to metabolism. 15-deoxy-δ12,14-PGJ2 has been shown to be a potent ligand for PPARγ. Metabolism of the cyclopentenone prostaglandins PGA2, PGJ2, and δ12-PGJ2 occurs via glutathione addition across the α,β unsaturated enone. CAY10410 was designed as an analog of the PPARγ-binding prostaglandins which could not undergo this conjugation reaction. In human neuroblastoma SH-SY5Y cells, CAY10410 was not cytotoxic at up to 25 μM. It also failed to covalently modify thioredoxin or induce oxidative stress at 50 μM.

TMB 8 is a non-competitive antagonist of nicotinic acetylcholine receptors (nAChRs) with IC50 values of 390 and 350 nM, respectively, for human muscle-type and α3β4 subunit-containing ganglionic nAChRs expressed in TE671/RD or SH-SY5Y cells. It inhibits nicotine-induced dopamine release from rat brain synaptosomes (IC50 = 480 nM). TMB 8 also reduces calcium availability in smooth and skeletal muscle, blocking the contractile response in isolated rabbit aortic strip when used at a concentration of 50 μM and inhibiting calcium influx and efflux in isolated guinea pig ileum when used at a concentration of 65 μM. It has been used in the study of intracellular calcium dynamics, particularly in smooth muscle. TMB 8 also inhibits protein kinase C (PKC) activity in a dose-dependent manner.

PDPOB is a phenyl carboxylic acid derivative with the potential to be used in the study of cerebral ischemia. PDPOB is shown to be protective against OGD/R-evoked multi-aspect neuronal deterioration in SH-SY5Y cells, as evidenced by reduced mitochondrial dysfunction, oxidative stress, and apoptosis [1].

PT-65, a potent and selective GSK3 degrader, demonstrates the highest degradation capacity for GSK3α (DC50 = 28.3 nM) and GSK3β (DC50 = 34.2 nM) in SH-SY5Y cells, making it applicable for Alzheimer's disease research [1].

MC2050 is a potent PARP-1 inhibitor. The IC50 for inhibition of PARP-1 activity is 119 nM, compared to 1.8 μM for PARP-2. MC2050 inhibits apoptosis and blocks poly ADP-ribosylation of histone H1 in hydrogen peroxide treated SH-SY5Y neuroblastoma cells.

Nerispirdine is a acetylcholine release enhancer, sodium channel blocker and K(V) 2.1 channel blocker. Nerispirdine inhibits voltage-dependent Na(+) channel currents recorded from human SH-SY5Y cells with an IC(50) of 11.9 micromol/L when measured from a

NMDA receptor antagonist-3 is a NMDA receptor antagonist with a significan recovery rate (40.0%, at 100 μM) and safe toxicological characteristics in SH-SY5Y and human adipose mesenchymal stem cells.

The neuroprotective effect of tubuloside B, one of the phenylethanoids isolated from the stems of Cistanche salsa, on tumor necrosis factor-alpha (TNFalpha)-induced apoptosis in SH-SY5Y neuronal cells.

Human GALP (3-32) (Galanin-like peptide (3-32)) serves as a high-affinity agonist for galanin receptors GalR1 (IC50 = 33 nM) and GalR2 (IC50 = 15 nM), as evidenced by competitive binding studies. It demonstrates significant potency in modifying the extracellular acidification rate in SH-SY5Y cells expressing GalR2 (EC50 = 360 nM) [1].

GPP 78 hydrochloride is a potent inhibitor of nicotinamide phosphoribosyltransferase (Nampt) with an IC50 of 3 nM for NAD depletion. GPP 78 hydrochloride is toxic to neuroblastoma cells SH-SY5Y via induction of autophagy with an IC50 of 3.8 nM. GPP78 has anticancer and anti-inflammatory effects.

GPP78 is a potent inhibitor of Nampt (IC50: 3.0 nM for nicotinamide adenine dinucleotide (NAD) depletion). GPP78 is cytotoxic to neuroblastoma cell line SH-SY5Y cells (IC50: 3.8 nM by inducing autophagy). GPP78 has anti-cancer and anti-inflammatory effect

Oxidopamine hydrobromide (6-OHDA hydrobromide) is a neurotransmitter dopamine antagonist.

AChE-IN-19 is a potent inhibitor of AChE (IC50: 0.56 μM) and also exhibits inhibition of Aβ aggregation. aChE-IN-19 exhibits neuroprotective effects and is virtually non-toxic to SH-SY5Y cells. aChE-IN-19 can be used to study Alzheimer's disease.

YM-244769 (3-Pyridinecarboxamide, N-[(3-aminophenyl)methyl]-6-[4-[(3-fluorophenyl)methoxy]phenoxy]-) is an effective inhibitor of Na+/Ca2+ exchange 3 (NCX3) with an IC50 of 18 nM. YM-244769 has efficient protective effects on neurons and kidneys.

Jionoside A1 is isolated and purified from the roots of Rehmannia glutinosa. It displays dose-dependent immune-enhancement activity and possesses moderate neuroprotective activities on H2O2-treated SH-SY5Y cells.

Lupiwighteone has anti-angiogenesis potential, it also has anticancer and cancer preventive effects on SH-SY5Y cells.