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Multitarget AD inhibitor-1 is a reversible and selective inhibitor of butyrylcholinesterase (BuChE) with IC50 values of 7.22 μM for human BuChE (hBuChE) and 1.55 μM for equine serum BuChE (eqBuChE). It also exhibits inhibitory activity towards β-secretase (IC50 41.60 μM), amyloid β aggregation (IC50 3.09 μM), and tau aggregation. As a diphenylpropylamine derivative, Multitarget AD inhibitor-1 is promising for research into multifunctional, disease-modifying treatments for Alzheimer's disease.

Spexin acetate is a potent galanin receptor 2/3 (GAL2/GAL3) agonist (EC50 values are 45.7 and 112.2 nM, respectively). Exhibits no significant activity at galanin receptor 1. Endogenous satiety-inducing peptide; inhibits long chain fatty acid uptake by ad

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].

1. Orientin (Luteolin-8-glucoside) may be regarded as a candidate therapeutic agent for treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway. 2. Orientin protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. 3. Orientin has neuroprotection effect by the intracellular mediation of caspase activity; may alleviate cognitive deficits and oxidative stress in AD mice; can exert antidepressant-like effects on CUMS mice, specifically by improving central oxidative stress, neurotransmission, and neuroplasticity.

Aftin-4, an amyloid forty-two inducer, activates γ-secretase, promoting the generation of amyloid-β-1-42 (Aβ1-42) from amyloid-β protein precursor. Aftin-4(Aftin4) increased Aβ-1-42, but not Aβ-1-40 in mouse hipppocampus, accompanied by learning deficits and mitochondrial ultrastructural changes similar to those found in the brains of patients with AD. Aftin-4(Aftin4) can thus be used to induce a rapid, acute Alzheimer's disease-like toxicity in the rodent brain.

TRAF6 peptide TFA, a specific inhibitor of the TRAF6-p62 interaction, significantly inhibits NGF-dependent ubiquitination of TrkA. This peptide demonstrates promising research applications in various neurological disorders, including Alzheimer's disease (AD), Parkinson's, ALS, head trauma, epilepsy, and stroke [1].

AChE BuChE MAO-B-IN-2 (compound 4b) is a potent inhibitor of AChE, BuChE, and hu MAO-B, with respective IC50 values of 5.3 μM, 12.4 μM, and 1.9±0.08 μM, indicating good in vitro blood-brain barrier (BBB) permeability. It effectively reduces excessive AChE and BuChE levels associated with Alzheimer's disease (AD) and holds potential for anti-Alzheimer's research [1].

Lp-PLA2-IN-14 (Compound 19), an inhibitor of rhLp-PLA2, exhibits a potent inhibitory effect with a pIC50 value of 8.4 and is applicable in research on neurodegenerative disorders including Alzheimer Disease (AD), glaucoma, age-related macular degeneration (AMD), and cardiovascular diseases such as atherosclerosis [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].

CNS-11, a compound that disaggregates tau fibrils, is utilized in Alzheimer's disease (AD) research [1].

Lp-PLA2-IN-10 is a potent inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2), formerly known as platelet-activating factor acetylhydrolase (PAF-AH). This enzyme catalyzes the hydrolysis of lipoprotein lipids or phospholipids. The compound has research potential in neurodegenerative diseases such as Alzheimer's disease (AD), as well as glaucoma, age-related macular degeneration (AMD), and cardiovascular diseases like atherosclerosis[1].

Y13g is a potent inhibitor of Interleukin-6 (IL-6) and acetylcholinesterase (AChE), both significant targets in Alzheimer's Disease (AD) progression. Y13g reverses memory deficits induced by STZ and demonstrates histopathology similar to that of normal animals [1].

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].

Bleformin A, a natural product isolated from Bletilla striata, serves as a potent butyrylcholinesterase (BChE) inhibitor, exhibiting an IC50 value of 5.2 μM. It is utilized in Alzheimer's disease (AD) research [1].

Lokivetmab, an Anti-Canine IL31 Recombinant Antibody, is a monoclonal antibody targeting canine IL-31, utilized in research related to atopic dermatitis (AD) in dogs [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].

BChE-IN-6 (compound 12) is a highly effective inhibitor of BChE with a Ki value of 0.182 μM, and it exhibits significant chelating abilities towards Zn 2+. These characteristics make BChE-IN-6 a valuable tool for researchers in the field of Alzheimer's disease (AD) [1].

α-Synuclein (61-95) (human) constitutes the hydrophobic core of α-synuclein and is implicated in inducing neuronal cell death. This segment is utilized in the study of neurodegenerative conditions such as Alzheimer's disease (AD) and Parkinson's disease (PD) [1] [2].

β-Amyloid (1-43)(human) TFA exhibits greater aggregation tendencies and heightened toxicity compared to Aβ1-42. This compound also associates with sAPPα and sAPPβ and 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) is the oxidized form of Methionine 35 in Aβ42, capable of producing an oligomer size distribution similar to Aβ40. This compound is utilized in Alzheimer’s disease (AD) research [1].

Rocatinlimab (AMG 451) (KHK4083) is a fully human, non-fucosylated IgG1 anti-OX40 monoclonal antibody indicated for atopic dermatitis (AD) research [1].

7-(4-Hydroxyphenyl)-1-phenyl-4-hepten-3-one as a beneficial compound to ameliorate the deleterious effects of Aβ on dendrite integrity and cell survival, and may provide new insights on drug discovery of Alzheimer's disease (AD).

BChE-IN-13 (Compound 17c) is an orally active, potent, and selective inhibitor of Butyrylcholinesterase (BChE), exhibiting IC50 values of 0.22 μM and 0.016 μM for eqBChE and hBChE, respectively. BChE-IN-13 enhances memory and cognitive impairments, making it valuable for Alzheimer's disease (AD) research [1].

Aβ-IN-6 is an orally active compound exhibiting anti-inflammatory, antioxidant, and anti-oligomeric activities, with significant implications for Alzheimer's disease (AD) research [1]. It effectively reduces the release of pro-inflammatory cytokines from microglia cells, promotes Nrf2 nuclear translocation, and impedes the formation of Aβ oligomers. Furthermore, Aβ-IN-6 demonstrates a stable neuroprotective effect by modulating redox-sensitive signaling pathways in an in vivo oxidative stress model.

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].

SAR502250 is a potent, selective, ATP-competitive, orally active, and brain-penetrant GSK3 inhibitor with a human GSK-3β IC50 value of 12 nM, exhibiting antidepressant-like activity and being researched for potential application in Alzheimer’s disease (AD) treatment.

AChE BChE MAO-B-IN-3, an indan-1-one derivative, is a potent inhibitor of human monoamine oxidase B (MAO-B) with an IC50 of 0.0359 μM and also demonstrates significant inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 0.0473 μM and 0.0782 μM, respectively. Exhibiting notable antioxidant activity, AChE BChE MAO-B-IN-3 holds considerable promise for Alzheimer's disease (AD) research.

AChE BChE MAO-B-IN-4, an indan-1-one derivative, is a potent inhibitor of monoamine oxidase B (MAO-B) and acetylcholinesterase butyrylcholinesterase (AChE BChE). It strongly inhibits human MAO-B with an IC50 of 0.0393 μM and is highly effective against human AChE and BChE with IC50 values of 0.0458 μM and 0.075 μM, respectively. Additionally, this compound exhibits significant antioxidant properties and ability to prevent β-amyloid plaque aggregation, suggesting its potential in Alzheimer's disease (AD) research.

sEH/AChE-IN-2 and acetylcholinesterase ( AChE ). sEH/AChE-IN-2 provides cumulative effects against neuroinflammation and memory impairment. sEH/AChE-IN-2 has the potential for the research of Alzheimer's disease (AD) .

Chalcones A-N-5, a trihydroxy chalcone derivative, exhibits no cytotoxicity at concentrations below 100 µM (with IC 50 > 1 mM) and notably enhances cell proliferation. It is particularly effective in encouraging neuronal cell growth within damaged brain tissue and demonstrates an ability to inhibit ferroptosis triggered by RSL or erastin, while also reducing lipid peroxidation levels associated with Aβ1-42 protein aggregation. Given these properties, Chalcones A-N-5 represents a promising molecular framework for further development as a lead compound in in vivo studies aimed at researching Alzheimer's Disease (AD) [1].

Blestrin D, a potent mixed-type butyrylcholinesterase (BChE) inhibitor with an IC50 value of 8.1 μM, is isolated from Bletilla striata and has applications in Alzheimer's disease (AD) research [1].

Leptin (116-130), a bioactive fragment of leptin, enhances synaptic plasticity in the hippocampus by promoting AMPA receptor trafficking to synapses. It preserves hippocampal synapse integrity and prevents neuronal cell death in amyloid toxicity models, showing promise for Alzheimer's disease (AD) research [1].

(1S,2R)-Alicapistat ((1S,2R)-ABT-957) is a highly efficient, orally active compound that selectively inhibits human calpains 1 and 2, showing promise for Alzheimer's disease (AD) therapy [1]. It effectively addresses the metabolic liability associated with carbonyl reduction and demonstrates potent inhibition of calpain 1 with an IC50 value of 395 nM [2].

sEH AChE-IN-1 (Compound 12a) is a dual inhibitor of soluble epoxide hydrolase (sEH) and acetylcholinesterase (AChE) with potential research applications in Alzheimer's disease (AD) due to its cumulative effect against neuroinflammation and memory impairment.

Zonisamide-13C2,15N is intended for use as an internal standard for the quantification of zonisamide by GC- or LC-MS. Zonisamide is an antiepileptic agent.1 It selectively inhibits the repeated firing of sodium channels (IC50 = 2 μg/ml) in mouse embryo spinal cord neurons and inhibits spontaneous channel firing when used at concentrations greater than 10 μg/ml.2 In rat cerebral cortex neurons, zonisamide (1-1,000 μM) inhibits T-type calcium channels with a maximum reduction of 60% of the calcium current.3 Zonisamide inhibits H. pylori recombinant carbonic anhydrase (CA) and the human CA isoforms I, II, and V with Ki values of 218, 56, 35, and 21 nM, respectively.4,5 In mice, it has anticonvulsant activity against maximal electroshock seizure (MES) and pentylenetetrazole-induced maximal, but not minimal, seizures (ED50s = 19.6, 9.3, and >500 mg/kg, respectively). Zonisamide (40 mg/kg, p.o.) prevents MPTP-induced decreases in the levels of dopamine , but not homovanillic acid or dihydroxyphenyl acetic acid , and increases MPTP-induced decreases in the dopamine turnover rate in mouse striatum in a model of Parkinson's disease.6 Formulations containing zonisamide have been used in the treatment of partial seizures in adults with epilepsy. |1. Masuda, Y., Ishizaki, M., and Shimizu, M. Zonisamide: Pharmacology and clinical efficacy in epilepsy. CNS Drug Rev. 4(4), 341-360 (1998).|2. Rock, D.M., Macdonald, R.L., and Taylor, C.P. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 3(2), 138-143 (1989).|3. Suzuki, S., Kawakami, K., Nishimura, S., et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res. 12(1), 21-27 (1992).|4. Nishimori, I., Vullo, D., Minakuchi, T., et al. Carbonic anhydrase inhibitors: Cloning and sulfonamide inhibition studies of a carboxyterminal truncated α-carbonic anhydrase from Helicobacter pylori. Bioorg. Med. Chem. Lett. 16(8), 2182-2188 (2006).|5. De Simone, G., Di Fiore, A., Menchise, V., et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: Solution and X-ray crystallographic studies. Bioorg. Med. Chem. Lett. 15(9), 2315-2320 (2005).|6. Yabe, H., Choudhury, M.E., Kubo, M., et al. Zonisamide increases dopamine turnover in the striatum of mice and common marmosets treated with MPTP. J. Pharmacol. Sci. 110(1), 64-68 (2009).

Prostaglandin J2 (PGJ2), a derivative of Prostaglandin D2 (PGD2), serves as a potent agonist for PGD2 receptors (DP), exhibiting affinity constants (K i) of 0.9 nM and 6.6 nM for hDP and hCRTH2 receptors, respectively. It activates cyclic AMP production with an EC50 of 1.2 nM, induces oxidative stress, neuronal apoptosis, and promotes the accumulation of ubiquitinated (Ub) proteins. Notably, PGJ2's neurotoxic properties are implicated in the progression of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD) [1] [2] [3] [4].

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, suggesting potential utility in Alzheimer’s disease (AD) research [1].

JWB1-84-1 3HCl, as a neuroprotective agent, can act by improving cognitive performances in a transgenic mouse model of AD.

BChE HDAC6-IN-1 is a dual BChE HDAC6 inhibitor exhibiting potent and selective inhibition with IC50 values of 4 nM for BChE and 8.9 nM for HDAC6. It demonstrates efficacy in alleviating cognitive deficits in an Aβ1–42-induced mouse model, indicating its potential utility in Alzheimer's disease research [1].

DDC 2′,3′-O-disulfate (compound 4) inhibits fibrillization and oligomerization of Aβ42, demonstrating potential for Alzheimer's disease (AD) research [1].

YIAD-0205, an orally administered inhibitor of Aβ(1-42) aggregation, has exhibited in vivo efficacy in a 5XFAD transgenic mouse model that harbors five familial AD mutations [1].

THK-5105, an arylquinoline derivative, demonstrates high binding affinity for tau fibrils, protein aggregates, and tau-rich Alzheimer's disease (AD) brain homogenates, indicating its potential as a tau imaging PET (Positron Emission Tomography) probe with the radiolabeled version, 18F-THK-5105 [1].

AChE BChE-IN-11 (compound 1), a natural product derived from artichoke leaves, is a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 70 μM and 71 μM, respectively. This compound is used in Alzheimer’s disease (AD) research [1].

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].

Bapineuzumab, an anti-β-amyloid protein (APP) monoclonal antibody, is utilized in Alzheimer’s disease (AD) research [1].

Alicapistat (ABT-957) is a human calpains 1 and 2 inhibitor. It can potentially be used to treat Alzheimer's disease (AD).

TML-6, an oral curcumin derivative, demonstrates inhibitory effects on the synthesis of β-amyloid precursor protein and β-amyloid (Aβ). Additionally, TML-6 exhibits upregulation of Apo E, suppression of NF-κB and mTOR, and enhancement of the anti-oxidative Nrf2 gene activity. Considering its diverse pharmacological profile, TML-6 holds promise as a valuable research tool for investigating Alzheimer's disease (AD)[1].

BChE-IN-2 (compound 22) is a highly effective inhibitor of BChE, with a Ki value of 0.099 μM, and represents a promising pyrimidine and pyridine derivative for investigating Alzheimer's disease (AD). [1]

Ensaculin is a NMDA antagonist and a 5HT1A agonist potentially for the treatment of Alzheimer's disease (AD). Ensaculin showed memory-enhancing effects in paradigms of passive and conditioned avoidance in both normal and artificially amnesic rodents. It e

Elenbecestat (E2609) is an effective oral bioutilization and CNS penetrating ACE-1 inhibitor for the treatment of Alzheimer's disease.

Zonisamide (AD 810), a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

Zonisamide sodium is a 1,2 benzisoxazole derivative. It is the first agent of this chemical class to be developed as an antiepileptic drug.