disease,neurotoxicity

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.

Oxidopamine hydrobromide (6-OHDA hydrobromide) is a widely used neurotoxin and an antagonist of the neurotransmitter dopamine. It selectively destroys dopaminergic neurons, promotes COX-2 activation, induces PGE2 synthesis, and stimulates the secretion of the pro-inflammatory cytokine IL-1β. It is commonly used to establish animal models of Parkinson’s disease (PD).

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 a widely used neurotoxin and an antagonist of the neurotransmitter dopamine. It selectively destroys dopaminergic neurons, promotes COX-2 activation, induces PGE2 synthesis, and stimulates the secretion of the inflammatory cytokine IL-1β. It is commonly used to establish animal models of Parkinson’s disease (PD).

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.

β-Amyloid (25-35) acetate is the Aβ(25-35) fragment of amyloid beta peptide, exhibiting neurotoxicity and commonly employed in constructing Alzheimer's disease cell and animal models.

Amyloid-β-IN-3 (EX.113) is a selective inhibitor of γ-secretase. It demonstrates inhibitory activity on Aβ42 secretion in H4 cells, with an EC50 value of 148 nM. By modulating the catalytic activity of γ-secretase, Amyloid-β-IN-3 decreases Aβ42 production, thereby alleviating neurotoxicity caused by Aβ deposition. It holds potential for Alzheimer's disease (AD) research.

PROTACGSK-3β Degrader-1 (compound 1) is a degrader targeting GSK-3β with an IC50 of 833 nM. This compound consists of SB-216763 (a GSK-3β inhibitor), a PEG linker, and CRBN (E3 ligase ligand). It reduces neurotoxicity induced by Aβ25-35 peptide and CuSO4 and is applicable in Alzheimer's disease research.

T 588 is an orally active neuroprotective agent that enhances acetylcholine release in the frontal cortex and hippocampus, thereby improving cognitive dysfunction. It safeguards cerebellar granule cells from glutamate-induced neurotoxicity and is applicable in neurological research, including studies on Alzheimer's disease.

Aβ aggregation-IN-4 reduces the neurotoxicity of β-amyloid protein (Aβ) and significantly decreases the levels of Aβ oligomeric complexes (Aβ-OCs), without affecting the overall levels of Aβ. It mitigates Aβ oligomerization and prevents oligomer-induced death of primary cortical neurons. Aβ aggregation-IN-4 is applicable in Alzheimer's disease (AD) research.

NSS-18 is a potent and reversible inhibitor of AChE and MAO-B, with IC50 values of 1.53 μM and 1.51 μM, respectively. It inhibits Aβ self-aggregation and reduces Aβ-induced intracellular ROS production. NSS-18 demonstrates moderate neuroprotective effects against 6-OHDA-induced neurotoxicity and forms chelates with metal ions such as Cu²⁺, Fe³⁺, and Zn²⁺, with the strongest chelation observed with Cu²⁺. This compound is applicable in Alzheimer's disease research.

α-Synuclein-IN-18 (Compound Mol D) is an inhibitor of the autocatalytic proliferation of α-synuclein (α-Synuclein) aggregates. It selectively binds to a conserved binding pocket on the surface of α-synuclein fibrils, delaying the aggregation process and tripling the aggregation T1/2. Furthermore, α-Synuclein-IN-18 reduces the formation of toxic α-synuclein oligomers, thereby mitigating neurotoxicity. This compound is valuable for Parkinson's disease research.

Memagal is an AchE inhibitor with an IC50 of 1.16 nM and an NMDAR antagonist with a Ki of 4.6 μM. It effectively suppresses NMDA-induced neurotoxicity, exhibiting an IC50 value of 0.28 nM. Memagal is applicable in Alzheimer's disease research.

β-Amyloid (1-42), rat/mouse TFA is a 42-amino-acid polypeptide fragment that exhibits neurotoxicity to hippocampal slices and is commonly used to establish Alzheimer's disease models for related 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)

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

NUCC-0000323 is a small molecule inhibitor of SOD1 (superoxide dismutase 1) expression. It functions by reducing the protein levels of SOD1 within cells. Since mutations and overexpression of SOD1 are closely linked to the pathogenesis of amyotrophic lateral sclerosis (ALS), NUCC-0000323 is utilized to study potential therapeutic strategies aimed at mitigating neurotoxicity and slowing disease progression by downregulating SOD1 expression.

SD-6 is an effective dual Jak2 and Aurora A kinase inhibitor. It inhibits tumor cell proliferation by blocking STAT3 phosphorylation and inducing mitotic arrest, used for hematological malignancy research.

S1R agonist 1 is a selective Sigma-1 receptor (S1R) agonist. It modulates calcium signaling and ER stress, used for Alzheimer's disease and neuropathic pain research.

Metrifonate is an organophosphorus prodrug that is metabolised non-enzymatically in the body to DDVP (dichlorvos), which acts as an irreversible cholinesterase (ChE) inhibitor. It inactivates ChE by phosphorylating the serine residue at its active site, making it useful for treating Alzheimer's disease and as an insecticide. Metrifonate affects AChE activity, oxidative stress, neurotoxicity, and cortisol levels in carp.

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].

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].

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.