neurodegeneration

Anti-neurodegeneration agent 1, a neurodegeneration-targeting agent.

Edicotinib (JNJ-527) is a brain penetrant and orally active inhibitor of the colony-stimulating factor-1 receptor (IC50: 3.2 nM). It shows less inhibitory effects on KIT and FLT3 (IC50: 20 nM and 190 nM). It has the potential for Alzheimer's disease and rheumatoid arthritis treatment.

Pyraclostrobin is one of the most heavily used fungicides that inhibits mitochondrial complex III of fungal and mammalian cells.

1. Octyl Gallate is an antioxidant approved by the US Food and Drug Administration (FDA) as a food additive. 2. Octyl Gallate has antimetastatic activity. 3. Octyl Gallate shows antimicrobial activity against H. pylori, with a minimum inhibitory concentration (MIC) value of 125 ug/mL. 4. Combination therapy with octyl gallate and ferulic acid improves cognition and neurodegeneration in a transgenic mouse model of Alzheimer's disease.5. Octyl Gallate is a potential anticancer agent, it exhibited decreased MCF-7 & MDA-MB-231 survival and induced apoptosis, with IC50 value of 40 uM. 6. Octyl gallate (Octyl 3,4,5-trihydroxybenzoate) has antiviral activity, it shows an inhibitory effect on the growth of herpes simplex virus type 1 (HSV-1) in HEp-2 or Vero cells. 7. Octyl gallate shows antifungal activity against Saccharomyces cerevisiae ATCC7754 and Zygosaccharomyces bailii ATCC 60483.

Lamivudine (BCH-189) is a reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.

NUCC-390, a novel small-molecule CXCR4 receptor agonist, selectively induces CXCR4 receptor internalization while acting antagonistically to AMD3100. This compound facilitates nerve functional recovery following neurodegeneration in vivo.

Ezeprogind disulfate is a neurotrophic inducer. Ezeprogind disulfate targets all causes of neurodegeneration including Abeta protein or tau protein. Ezeprogind disulfate can be used for the research of neurological disorders, including progressive supranu

Vutiglabridin (HSG4112) is a novel and safe modulator of PON2, a racemic compound. vutiglabridin is an optimized structural analogue of Glabridin and is superior to Glabridin in terms of weight loss and chemical stability. vutiglabridin ameliorates mptp-induced neurodegeneration in Parkinson's disease mice by targeting mitochondrial paraoxonase-2. Vutiglabridin is a clinical phase 2 drug for the treatment of obesity and has therapeutic effects on p-mitochondrial PON2 in a PD model. vutiglabridin penetrates the brain, binds PON2, and restores 1-methyl-4-phenylpyridine (MPP*)-induced neuroblastoma in SH-SY5Y Vutiglabridin significantly attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dyskinesia and dopaminergic neuronal damage in mice modeled with PD in mouse experiments.

Pyridostatin (RR82) is a synthetic small-molecule stabilizer of G-quadruplexes, a secondary structure of DNA that usually exists in the end of the chromosome or the telomeres.

1. Isoquercetin (3-Glucosylquercetin) is a potential stimulator of bone mineralization used for prophylaxis of osteoporotic disorders. 2. Isoquercetin may be as a potential therapeutic agent against neurodegeneration in Parkinson's disease. 3. Isoquercetin is an inhibitor of Wnt/β-catenin and may be as a potential novel anti-tumoral agent, such as against human pancreati,liver cancer related to opioid receptors and to the activation of the mitogen-activated protein kinase (MAPK) signalling pathway. .

BAF312 (Siponimod (BAF-312)), a next-generation S1P receptor modulator, is specific for S1P1 and S1P5 receptors with EC50 of 0.39 nM and 0.98 nM, respectively. The specificity of BAF312 for S1P1 and S1P5 receptors exhibits >1000-fold over S1P2, S1P3 and S1P4 receptors.

1. Vitexin has antinociceptive and antispasmodic activities. 2. Vitexin exhibits a prominent first-pass effect. 3. Vitexin has antioxidant, antimyeloperoxidase, and α-glucosidase inhibitory activities. 4. Vitexin can either inhibit or induce activities of

BI-6C9 is an inhibitor of tBid (Kd = 20 µM).BI-6c9 prevented MOMP and mitochondrial fission, and protected the cells from cell death.

Cucurbitacin E is a natural product isolated from the climbing stem of Cucumic melo L. It significantly suppresses the activity of the cyclin B1 CDC2 complex.Cucurbitacin E has prevention of neurodegeneration, it has potent anti-proliferative, antineoplas

GKT136901 (AK120765) is an inhibitor of NOX1 4.It acts as Selective and Direct Scavenger of Peroxynitrite

Laquinimod (LAQ) is an effective immunomodulator, which is currently under development in phase III trials for the treatment of multiple sclerosis as an oral therapy.

Pyridostatin Trifluoroacetate Salt is a G-quadruplexe stabilizer with Kd of 490 nM in a cell-free assay, which targets a series of proto-oncogenes including c-kit, K-ras and Bcl-2.

AK-1 is a sirtuin 2 (SIRT2) inhibitor (IC50:12.5 µM).that prevents hippocampal neurodegeneration in Alzheimer's disease models and induces cell cycle arrest in colon carcinoma cells.

ATX inhibitor 10 is a nitrogen-containing heterocyclic compound that is a potent inhibitor of ATX. Among other things, ATX plays a role in causing pathologies including fibrosis, neurodegeneration, arthritis, neuropathic pain, and cancer. ATX inhibitor 10 has shown research potential for ATX-related diseases.

Geissoschizoline ((+)-Geissoschizoline), with IC50 values of 20.40 µM for human AChE and 10.21 µM for BChE, functions as a potent inhibitor and emerges as a promising multi-target prototype for research into preventing neurodegeneration and restoring neurotransmission. Additionally, it serves as a potent anti-inflammatory agent.

TSPO ligand-1 has affinity for peripheral and central benzodiazepine receptors.TSPO ligand-1 is an AUTAC4-binding protein in the transmembrane domain of the outer mitochondrial membrane, which induces mitochondrial autophagy and promotes intracellular mitochondrial regeneration.TSPO ligand-1 is involved in intracellular cholesterol transport, and can be used as a biomarker for brain injury and neurodegeneration. TSPO ligand-1 is involved in intracellular cholesterol transport and can be used as a biomarker for brain damage and neurodegeneration.

K6PC-5 is a ceramide derivative that acts as an activator of sphingosine kinase 1 (SPHK1), inducing a swift and temporary rise in intracellular calcium levels. With its potential applications in skin diseases associated with abnormal keratinocyte function, as well as in studies on neurodegeneration and virus infection, K6PC-5 presents a promising compound for research purposes.

Arachidoyl ethanolamide, a saturated fatty acyl ethanolamide lacking classical (CB1/CB2) activity, plays a role in a complex system comprising central cannabinoid (CB1), peripheral cannabinoid (CB2), and non-CB receptor-mediated pharmacology. This system has paved the way for extensive research in diverse fields such as memory, weight loss and appetite, neurodegeneration, tumor surveillance, analgesia, and inflammation. Unlike other compounds, Arachidoyl ethanolamide does not bind to the murine CB1 receptor nor does it compete with anandamide for the fatty acid amide hydrolase, the endocannabinoid hydrolytic enzyme. The non-CB receptor-mediated actions of saturated ethanolamides like Arachidoyl ethanolamide are currently under investigation.

The P7C3 class of neuroprotective aminopropyl carbazoles has been shown to block neuronal cell death in models of neurodegeneration. We now show that P7C3 molecules additionally preserve axonal integrity after injury, before neuronal cell death occurs, in

Oleoylcarnitine (Oleoyl-L-carnitine) inhibits adenine nucleotide translocase (AdNT) activity with an ic50 of 14 μM.Oleoylcarnitine is an important indicator of neurodegeneration.

Kynurenic acid (Quinurenic acid) is an endogenous tryptophan active metabolite, a triple antagonist of NMDA, glutamate, α7 nicotinic acetylcholine receptor, and an agonist of GPR35/CXCR8 with neuroprotective and anticonvulsant properties. It has neuroprotective and anticonvulsant properties and can be used to study neurodegeneration and metabolism-related diseases.

hMAO-B MB-COMT-IN-2 is a dual inhibitor of MAO-B MB-COMT with IC50s of 4.27 μM and 2.69 μM for hMAO-B and MB-COMT, respectively. hMAO-B MB-COMT-IN-2 protects cells from oxidative damage and can be used in neurodegeneration disease research, such as Parkinson’s Disease (PD) [1].

Rocaglaol is a potent anticancer drug that induces apoptosis of LNCaP cells through the mitochondrial pathway and its G2/M-phase cell cycle arrest is associated with the down-regulation of Cdc25C and the dephosphorylation of Cdc2. Rocaglaol can reduce tis

H3 receptor-MO-1, a potent modulator of the histamine H3 receptor (H3 receptor), can be utilized to study neurodegeneration and cognitive disorders.

Ezeprogind (AZP-2006) is an orally active neurotrophic inducer with potent neuroprotective properties, addressing underlying factors of neurodegeneration beyond conventional targets like Abeta protein and tau protein. It is a valuable tool for studying neurological disorders such as progressive supranuclear palsy (PSP), tauopathies, Alzheimer's disease, and Parkinson's disease.

NUCC-390 dihydrochloride, a novel and selective CXCR4 receptor agonist, effectively induces the internalization of CXCR4 receptors and acts antagonistically to AMD3100 [1]. This small-molecule compound has demonstrated the ability to facilitate functional nerve recovery following neurodegeneration in vivo [2].

DOPAL is an aldehyde product of the oxidative deamination of dopamine by monoamine oxidase.[1] It can be further oxidized to 3,4-dihydroxyphenylacetic acid (DOPAC) by aldehyde dehydrogenase (ALDH) and, to a lesser extent reduced to 3,4-dihydroxyphenyl ethanol (DOPET). DOPAL is toxic to neurons.[2],[3] It can also oligomerize and precipitate α-synuclein, an event associated with Parkinson's disease.[2] Mice lacking cytosolic and mitochondrial forms of ALDH display increased levels of DOPAL as well as neurodegeneration and motor dysfunction characteristic of Parkinson’s disease.[4]

hAChE-IN-3 (compound 5c) serves as a potent inhibitor for AChE, BuChE, MAO-B, and BACE-1, with respective IC50 values of 0.44, 0.08, 5.15, and 0.38 μM, demonstrating its ability to cross the blood-brain barrier. This compound also exhibits antioxidant properties and metal chelation capabilities. Additionally, it targets peripheral anion sites, potentially modulating β-amyloid and ameliorating neurodegeneration linked to Alzheimer's disease, highlighting its research potential for this condition [1].

Fosmetpantotenate, a immunomodulator, is used for treatment of Pantothenate Kinase Associated Neurodegeneration (PKAN).

C2-8 is an inhibitor of polyglutamine (polyQ) aggregation with IC50s of 25 and 0.05 μM for recombinant HDQ51 and in PC12 cells, respectively. It also limits polyQ aggregation in organotypic hippocampal slice cultures from R6 2 transgenic mice and reduces neurodegeneration dose-dependently in a Drosophila model of Huntington's disease. C2-8 (100 and 200 mg kg) decreases huntingtin aggregate size, reduces neuronal atrophy, and enhances motor performance in a rotarod test in the R6 2 transgenic mouse model of Huntington's disease.

Kynurenic acid, an active metabolite of tryptophan, is synthesized through a kynurenine intermediate by kynurenine aminotransferases (KATs). It acts as an antagonist of both NMDA and AMPA receptors, as well as α7 nicotinic acetylcholine receptors (nAChRs; EC50s = 235, 101, and 7 µM, respectively), and functions as an agonist for the aryl hydrocarbon receptor (AhR) and G protein-coupled receptor 35 (GPR35; EC50s = 1.4 and 39 µM, respectively). In a neonatal rat model of cerebral hypoxic-ischemia, induced by carotid artery ligation, administration of kynurenic acid at 300 mg/kg prevents weight loss in the lesioned hemisphere. Additionally, at concentrations of 1 and 5 mg/ml, it protects against neurodegeneration in the rhabdomere of the eye in an Htt93QtransgenicDrosophila model of Huntington's disease. Elevated levels of kynurenic acid in the cerebrospinal fluid have been observed in patients with schizophrenia.

PMX-205 is a cyclic hexapeptide that acts as a potent antagonist of C5a receptor (C5aR; IC50= 31 nM).1It is orally active and blocks inflammatory signaling and symptoms in animal models of colitis and allergic asthma.2,3PMX-205 is also brain penetrant and reduces neuroinflammation and neurodegeneration in an animal model of Alzheimer's disease.4 1.March, D.R., Proctor, L.M., Stoermer, M.J., et al.Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes. Relationships between structures and activityMol. Pharmacol.65(4)868-879(2004) 2.Jain, U., Woodruff, T.M., and Stadnyk, A.W.The C5a receptor antagonist PMX205 ameliorates experimentally induced colitis associated with increased IL-4 and IL-10Br. J. Pharmacol.168(2)488-501(2013) 3.Staab, E.B., Sanderson, S.D., Wells, S.M., et al.Treatment with the C5a receptor/CD88 antagonist PMX205 reduces inflammation in a murine model of allergic asthmaInt. Immunopharmacol.21(2)293-300(2014) 4.Fonseca, M.I., Ager, R.R., Chu, S.-H., et al.Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's diseaseJ. Immunol.183(2)1375-1383(2009)

β-Amyloid (1-16) rat is a fragment of the amyloid beta (Abeta) peptide's metal-binding domain, containing three amino acid substitutions compared to its human counterpart, which confer reduced susceptibility to Alzheimer's disease-like neurodegeneration in rats and mice [1].

Beclin1-Bcl-2 Interaction Inhibitor 1 effectively disrupts the binding of Beclin 1 to Bcl-2, and is utilized in cancer and neurodegeneration research [1].

Laquinimod (ABR-215062) sodium is a carboxamide derivative administered orally that serves as a powerful immunomodulator, designed to prevent inflammation and neurodegeneration within the central nervous system. This compound effectively diminishes the activation of astrocytic NF-κB, offering protection against Cuprizone-induced demyelination. It shows promise for the treatment of both relapsing-remitting (RR) and chronic progressive (CP) forms of multiple sclerosis (MS; RRMS or CPMS), in addition to its potential applications in the study of neurodegenerative diseases [1] [2] [3] [4].

C-ABL-IN-1 is a new and specific inhibitor of the c-Abl protein, which effectively prevents the progression of neurodegeneration observed in Parkinson's disease.

GKT136901 hydrochloride is a powerful, selective, and orally active inhibitor of NADPH oxidase (NOX1 4). It exhibits K i values of 160 nM and 165 nM against NOX1 and NOX4, respectively. Additionally, GKT136901 hydrochloride demonstrates selectivity and direct scavenging ability towards peroxynitrite. This compound finds utility in studying diabetic nephropathy, stroke, neurodegeneration, and possesses anti-inflammatory properties.

hMAO-B MB-COMT-IN-1 is a dual MAO-B MB-COMT inhibitor with IC50s of 2.5 μΜ for hMAO-B and 3.84 μΜ for MB-COMT. hMAO-B MB-COMT-IN-1 protects cells from oxidative damage and can be utilized in neurodegenerative disease research, such as Parkinson's Disease (PD) [1].