alzheimer’s

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.

Deferoxamine Mesylate (DFOM) is an iron chelator and ferroptosis inhibitor. Deferoxamine Mesylate binds free iron into a stable complex and reduces iron accumulation. Deferoxamine Mesylate up-regulates HIF-1α levels and induces apoptosis.

Nicotinamide riboside increases NAD[+] levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high fat diet-induced metabolic abnormalities.

BuChE-IN-TM-10 (TM-10) is a potent inhibitor of butyrylcholinesterase (BuChE), exhibiting an IC50 of 8.9 nM. It effectively inhibits and disaggregates self-induced Aβ aggregation, displays significant antioxidant activity, and demonstrates substantial penetration through the blood-brain barrier (BBB). TM-10 holds promise as a potential treatment for Alzheimer’s disease.

5-Bromo-2’,3’,5’-tri-O-acetyluridine is a purine nucleoside analog that is being explored to improve Alzheimer’s and Parkinson’s diseases.

MS8511, a selective covalent irreversible inhibitor of G9a/GLP, targets a cysteine residue at the substrate binding site, displaying IC50 values of 100 nM (G9a) and 140 nM (GLP), alongside Kd values of 44 nM (G9a) and 46 nM (GLP). This compound effectively reduces cellular H3K9me2 levels and boosts antiproliferation activity, making it applicable in cancer research involving brain, breast, ovarian, lung, bladder, melanoma, and colorectal cancers, as well as studies on Alzheimer’s disease (AD), sickle cell disease, and Prader−Willi syndrome (PWS) [1].

CM-675 is a dual inhibitor of phosphodiesterase 5 (PDE5) and class I histone deacetylases (IC50s: 114 nM and 673 nM for PDE5 and HDAC1) with the potential to treat Alzheimer’s disease.

1. Sinapine, an alkaloid from seeds of the cruciferous species, can be used as an effective natural compound for chemo-resistance. 2. Sinapine has antioxidant and radio-protective activities.

740 Y-P (740YPDGFR) is a potent and cell-permeable activator of PI3K.

Jatrorrhizine (neprotin) is a protoberberine alkaloid isolated from Enantia chlorantha (Annonaceae) and other species. It was found to have antimicrobial and antifungal activity. It binds and noncompetitively inhibits monoamine oxidase (IC50 4 micromolar for MAO-A and 62 for MAO-B).

Isonaringin shows anti-Alzheimer’s activity by inhibiting AChE.

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].

Sinapine hydroxide, an alkaloid derived from the seeds of cruciferous plants, demonstrates a variety of beneficial properties including anti-inflammatory, anti-oxidant, anti-tumor, anti-angiogenic, and radio-protective effects. Additionally, it acts as an inhibitor of acetylcholinesterase (AChE), making it valuable for researching neurodegenerative conditions such as Alzheimer’s disease, ataxia, myasthenia gravis, and Parkinson’s disease[4].

FITC-β-Ala-Amyloid β-Protein (1-42) ammonium, a fluorescein isothiocyanate (FITC)-tagged monomer peptide of Aβ1-42, is instrumental in Alzheimer’s disease pathogenesis [1].

Methyl ganoderate A acetonide, a lanostane triterpene derived from the fruiting bodies of Ganoderma lucidum, serves as a potent acetylcholinesterase (AChE) inhibitor with an IC50 value of 18.35 μM. Its efficacy in inhibiting AChE suggests potential utility in Alzheimer’s disease (AD) research [1].

β-Amyloid precursor protein (96-110), cyclized (human), a segment of the amyloid precursor protein, serves as a research tool in Alzheimer’s disease studies [1].

hAChE-IN-5 (compound 49) is a dual inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBuChE), exhibiting inhibitory potency with IC50 values of 0.17 μM for both enzymes. Additionally, it demonstrates potent glycogen synthase kinase 3 beta (GSK3β) inhibition with an IC50 of 0.21 μM. The compound is an effective inhibitor of tau protein and Aβ1-42 peptide self-aggregation. It can virtually bind the peripheral anionic site (PAS), preventing amyloid-beta (Aβ)-induced neurotoxicity. hAChE-IN-5's ability to cross the blood-brain barrier (BBB) underpins its utility in the development of multitargeted anti-Alzheimer’s agents [1].

C5aR1 antagonist peptide, a biologically active linear peptide originating from the C-terminus of the chemokine complement fragment 5 anaphylatoxin (C5a), inhibits C5a binding and activity at human and rat C5a receptors. Overexpression of C5a is linked to various immunoinflammatory diseases, including arthritis, Alzheimer’s disease, cystic fibrosis, and systemic lupus erythematosus.

Acetyl-β Amyloid (15-20), Amide is a peptide fragment that inhibits β-sheet formation and stabilizes the structure of the Aβ (1–40) peptide, making it a useful tool in Alzheimer’s disease research [1].

Memogain is a pro-drug of galantamine. It is used for the treatment of Alzheimer’s disease.

Anionic interaction of Beta-amyloid (1-11) with Factor XII is suspected to cause massive activation of the C4 (complement 4) system in the cerebrospinal fluid of Alzheimer’s disease patients.

Glycerophosphorylethanolamine is an active phosphodiester metabolite of phosphatidylethanolamine.1,2It promotes aggregation of amyloid-β (1-40) (Aβ40)in vitro, and levels of glycerophosphorylethanolamine are elevated in postmortem brains isolated from patients with Alzheimer’s disease. 1.Klunk, W.E., Xu, C.J., McClure, R.J., et al.Aggregation of β-amyloid peptide is promoted by membrane phospholipid metabolites elevated in Alzheimer’s disease brainJ. Neurochem.69(1)266-272(1997) 2.Blusztajn, J.K., Lopez Gonzalez-Coviella, I., Logue, M., et al.Levels of phospholipid catabolic intermediates, glycerophosphocholine and glycerophosphoethanolamine, are elevated in brains of Alzheimer’s disease but not of Down’s syndrome patientsBrain Res.536(1-2)240-244(1990)

Vanutide cridificar (ACC-001) is an aminoterminal Aβ1-7 peptide conjugate, employed in Alzheimer’s disease (AD) research [1].

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

Solanezumab, a humanized monoclonal IgG1 antibody targeting the mid-domain of the amyloid-β (Aβ) peptide, shows promise for Alzheimer’s disease research [1].

Potent somatostatin receptor 1 (sst1) agonist; displays selectivity for sst1 (IC50 values are 30.9 nM, 345 nM, > 1 μM, > 10 μM and > 10μM for human sst1, sst3, sst4, sst2 and sst5 respectively). Attenuates somatostatin release in the rat nucleus accumbens

AChE/BChE-IN-14 (compound 13), a benzylisoquinoline alkaloid extracted from Fissistigma polyanthum roots, demonstrates inhibitory effects on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), coupled with antioxidant properties. This compound is pertinent to Alzheimer’s disease research [1].

PDE5-IN-10 (compound 4b), a potent phosphodiesterase type 5 (PDE5) inhibitor, exhibits an effective half-maximal inhibitory concentration (IC50) of 20 nM, enhanced in vitro microsomal stability (t 1/2 = 44.6 min), and excellent efficacy in restoring long-term potentiation, making it suitable for Alzheimer’s disease (AD) research [1].

Jatrorrhizine chloride (Neprotine chloride) is a potent and orally active uptake-2 transporter inhibitor. It exhibits a critical neuroprotective role in H2O2-induced apoptosis via inhibition of the MAPK pathway in HT22 hippocampal neurons.

Tenuifolin has no inherent toxicity to either the transfected or wild type cells at the effective concentrations, it inhibits amyloid-β secretion in vitro.

CM-414 is a dual inhibitor of HDACs and PDE5 for the Treatment of Alzheimer’s Disease (IC50 values of 60 nM, 310 nM, 490 nM, 322 nM, and 91 nM against PDE5, HDAC1, HDAC2, HDAC3, and HDAC6, respectively). Chronic treatment of Tg2576 mice with CM-414 dimini

JNK3 Inhibitor-3 (compound 15g) is a selective, blood-brain barrier permeable, and orally active inhibitor of c-Jun N-terminal kinase 3 (JNK3) with IC50 values of 147.8 nM, 44.0 nM, and 4.1 nM against JNK1, JNK2, and JNK3, respectively. This compound has been shown to significantly enhance memory in mouse models of dementia and is utilized in Alzheimer’s disease research [1].

Dual AChE-MAO B-IN-5, an indanone derivative, serves as an effective dual inhibitor for AChE and MAO-B, displaying IC50 values of 0.0224 μM for AChE, 0.0412 μM for MAO-B, and 0.1116 μM for MAO-A. Additionally, it exhibits antioxidant properties and inhibits β-amyloid plaque aggregation, making it suitable for Alzheimer’s disease (AD) research.

JNK3 Inhibitor-8 is a potent, selective, and orally active inhibitor that can cross the blood-brain barrier, targeting JNK3 with IC50 values of 21 nM for JNK3, 2203 nM for JNK2, and >10000 nM for JNK1. This compound demonstrates significant neuroprotective effects and holds promise for Alzheimer’s disease (AD) research [1].

β-Amyloid (1-43)(human) TFA exhibits greater aggregation tendencies and heightened toxicity compared to its well-established counterpart, Aβ1-42. Additionally, this compound demonstrates associations with both sAPPα and sAPPβ. It has the potential to serve as an additional biomarker for Alzheimer’s disease (AD), complementing existing markers [1].

(Met(O)35)-Amyloid β-Protein (1-42) represents the oxidized form of Methionine 35 in Aβ42, capable of producing an oligomer size distribution akin to that of Aβ40. This compound is utilized in Alzheimer’s disease (AD) research [1].

Gosuranemab (BMS-986168), a humanized IgG4 anti-tau monoclonal antibody, specifically targets human N-terminal tau residues 15-22. It holds potential for Alzheimer’s disease (AD) research [1] [2].

β-Amyloid (1-14),mouse,rat is a 1 to 14 fragment of Amyloid-β peptide. β-Amyloid (1-14),mouse,rat is produced through the proteolytic processing of a transmembrane protein, amyloid precursor protein (APP), by β- and γ-secretases. β-Amyloid (1-14),mouse,rat accumulation in the brain is proposed to be an early toxic event in the pathogenesis of Alzheimer’s disease, which is the most common form of dementia associated with plaques and tangles in the brain[1]. [1]. Chen GF, et al. Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol Sin. 2017 Sep;38(9):1205-1235.

GOAT-IN-1 is an inhibitor of ghrelin O-acyltransferase (GOAT), which could be useful for the prophylaxis or treatment of diabetes, hyperlipidemia, non-alcoholic fatty liver, Alzheimer’s disease, Parkinson’s disease, cerebrovascular dementia, cerebral infa

Glutaminyl Cyclase Inhibitor 3, a designed anti-Alzheimer’s compound, is a potent human Glutaminyl Cyclase (GC) inhibitor (IC50: 4.5 nM). It significantly reduced the brain concentrations of pyroform Aβ and total Aβ and restored cognitive functions.

L-Threonic acid magnesium salt (L-TAMS) increases synapse density and memory ability in both aged rats and late stage Alzheimer’s disease (AD) model mice.

AD-35 is a neuroprotectant for treating Alzheimer’s diseases by significantly inhibiting the production and release of proinflammatory cytokines TNF-α and IL-1β.

SEW 2871 is an orally available, highly selective S1P1 agonist with an EC50 of 13.8 nM.It reduces the number of lymphocytes in the blood and is used in studies related to diabetes, Alzheimer's disease, liver fibrosis, and inflammation. It activates ERK, Akt and Rac signaling pathways and induces S1P1 internalization and recycling.

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

β-Amyloid (11-22) is a peptide fragment of β-Amyloid.Beta-amyloid peptide (Abeta), the major constituent of amyloid plaques in the brains of Alzheimer’s patients, is thought to be the cause of Alzheimer’s Disease (AD). AD is the most common neurodegenerat

Dyrk1A-IN-3 (Compound 8b) is a highly selective inhibitor of dual-specificity tyrosine-regulated kinase 1A (DYRK1A). Dyrk1A-IN-3 has high binding affinity of DYRK1A with an IC 50 of 76 nM. Dyrk1A-IN-3 can be used in neurodegenerative disorders research, for example, Alzheimer’s Disease, Huntington’s Disease, and Parkinson’s Disease [1].

VU0357017 hydrochloride (ML071 hydrochloride) is highly selective M1 agonists act at an allosteric site to activate the receptor (EC50: 477 ± 172 nM; Pec50: 6.37 ± 0.15).

Dehydrodiscretamine chloride, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), exhibits IC50 values of 17.8 μM and 118.8 μM, respectively. It also possesses antioxidant activity and is utilized in research related to Alzheimer’s disease [1].

AChE/BChE-IN-15 (Compound 6d) serves as an inhibitor for both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), presenting inhibition constants (IC50) of 20 nM for AChE and 220 nM for BChE. It interacts with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) within the enzymes' active sites. AChE/BChE-IN-15 is applicable in Alzheimer’s disease research [1].

PD25, an inhibitor of both AChE and BuChE, demonstrates inhibitory constants of hAChE IC50: 1.58 μM, eeAChE IC50: 1.63 μM, and eqBuChE IC50: 2.39 μM. It exhibits antioxidant properties with a DPPH IC50 of 29.55 μM. This compound is utilized in the research of Alzheimer’s disease [1].