disease,neurotoxicity

Copper histidine inhibited Ctr1-mediated cellular uptake of oxaliplatin in vitro without altering oxaliplatin accumulation of platinum or neurotoxicity in DRG tissues in vivo. Copper histidine is administered orally for the treatment of Menkes disease.

Orphenadrine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that inhibits clonal HERG channels in a concentration-dependent manner, producing an IC of 0.85 μM in HEK cells.Orphenadrine is an antagonist of central and peripheral muscarinic receptors. Attenuation is blocked by mutations in pore residues Y652 or F656. Orphenadrine has antispasmodic, analgesic, and anticholinergic activity and protects against glutamatergic neurotoxicity in vitro and in vivo.Orphenadrine has inhibitory effects on sodium channels and can be used in the treatment of Parkinson's disease.

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

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

BML-259 is an inhibitor of CDK5 and CDK2 with IC50s of 64 and 98 nM, respectively. BML-259 can be used in studies about the treatment of cancer and neurodegenerative diseases.

SD-6, an orally active inhibitor targeting both hAChE and hBChE, demonstrates IC50 values of 0.907 µM and 1.579 µM, respectively. With its excellent blood-brain barrier (BBB) permeability and lack of neurotoxicity, SD-6 holds potential for Alzheimer's disease research.

D-DOPA is an enantiomer of the dopamine precursor L-DOPA . It can be converted to L-DOPAviasequential oxidation and transamination, which are mediated by D-amino acid oxidase (DAAO) and DOPA transaminase, respectively, in rat kidney homogenates.1It reduces the number of dopaminergic neurons in primary rat embryonic mesencephalic cultures in a concentration-dependent manner.2Intraventricular administration of D-DOPA (200 μg/animal) increases striatal dopamine levels in rats.3D-DOPA (20 mg/kg, i.p.) induces contralateral turns in a rat model of Parkinson's disease induced by 6-OHDA .4 1.Wu, M., Zhou, X.-J., Konno, R., et al.D-dopa is unidirectionally converted to L-dopa by D-amino acid oxidase, followed by dopa transaminaseClin. Exp. Pharmacol. Physiol.33(11)1042-1046(2006) 2.Ling, Z.-D., Pieri, S.C., and Carvey, P.M.Comparison of the neurotoxicity of dihydroxyphenylalanine stereoisomers in cultured dopamine neuronsClin. Neuropharmacol.19(4)360-365(1996) 3.Karoum, F., Freed, W.J., Chuang, L.-W., et al.D-dopa and L-dopa similarly elevate brain dopamine and produce turning behavior in ratsBrain Res.440(1)190-194(1988) 4.Moses, J., Siddiqui, A., and Silverman, P.B.Sodium benzoate differentially blocks circling induced by D-and L-dopa in the hemi-parkinsonian ratNeurosci. Lett.218(3)145-148(1996)

Humanin, a 24-amino acid anti-apoptotic peptide and Bax inhibitor, prevents Bax translocation from the cytosol to mitochondria and obstructs its activation. This mitochondria-associated peptide has neuroprotective properties against Alzheimer's Disease (AD)-related neurotoxicity and enhances insulin sensitivity in animals, linking it to aging processes [1] [2]. An analogue named HNG, with serine at position 14 substituted for glycine, has been developed [2].

AG-825（Tyrphostin C15） is a selective and competitive ErbB2 inhibitor that inhibits tyrosine phosphorylation with an IC50 value of 0.35 μM.AG-825 (Tyrphostin C15) inhibits HER2 and shows anticancer activity in a mouse xenograft model of breast cancer.AG-825 ( Tyrphostin C15) is a potentially active molecule for overcoming manganese-induced neurotoxicity or the development of Alzheimer's disease, and promotes apoptosis in human neutrophils, which could be used in the study of breast cancer.

Tricetin is a flavonoid isolated from pomegranate.Tricetin is a potent competitive inhibitor of Keap1-Nrf2 protein-protein interaction (PPI) and protects Parkinson's disease patients from 6-OHDA-induced neurotoxicity by activating the Nrf2 HO-1 signaling pathway and blocking mitochondria-dependent apoptotic pathways.Tricetin Inhibits migration and expression of the indicator protease progerin-1 (PS-1) in nasopharyngeal carcinoma through the Akt GSK-1β pathway.Tricetin inhibits endothelial inflammation induced by oxidized LDL mediated by Egr-1, and protects rat chondrocytes from IL-1β-induced inflammation and apoptosis.Tricetin is an inhibitor of endothelial inflammation induced by oxidized LDL mediated by Egr-1 and protects against IL-1β-induced inflammation and apoptosis.

GSK-3β inhibitor 15 (Compound 54), with an IC50 of 3.4 nM, effectively suppresses Aβ 1-42-induced phosphorylation of GSK-3β and tau protein, as well as LPS-induced iNOS expression, demonstrating neuroprotective properties against Aβ 1-42-induced neurotoxicity and indicating potential utility in Alzheimer's disease (AD) research [1].

1. Talatisamine (12 μM) and TEA (5mM) inhibits the enhanced I(K) caused by Aβ4 oligomers, attenuates cytotoxicity of Aβ oligomers by restoring cell viability and suppressing K(+) loss related apoptotic response. 2. Talatisamine can therefore be considered

β-Amyloid (1-40), England mutation, is a biologically active peptide with a histidine (His) to arginine (Arg) substitution at position 6, known to enhance oligomerization kinetics that serve as fibril seeds and increase neurotoxicity in cultured neurons. This alteration is one of several mutations in the beta-amyloid precursor gene implicated in autosomal dominant Alzheimer's Disease across multiple kindreds.

Compound AK-2, also known as hAChE hBACE-1-IN-4, is a quinazoline derivative that demonstrates significant inhibitory activity against the enzymes hAChE and hBACE-1 (hAChE, IC 50 = 0.283 μM; hBACE-1, IC 50 = 0.231 μM). This compound also shows potential in inhibiting Aβ aggregation and possesses characteristics such as non-neurotoxicity, blood-brain barrier permeability, and oral activity, making it a valuable agent for research in Alzheimer's disease [1].