disease (ad)

Aducanumab (BIIB037), A selective human immunoglobulin gamma-1 (IgG1) monoclonal antibody, targets the clustered form of amyloid beta (Aβ). Aducanumab shows brain permeability and may be used to treat Alzheimer's disease (AD).

PPI-1019 is an APP (β-amyloid A4) inhibitor for the treatment of neurological disorders and the study of Alzheimer's disease (AD).

Sembragiline (EVT-302) is a selective MAO-B inhibitor for the study of Alzheimer's disease (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].

AVN 322 free base is an orally available, selective and potent 5-HT6R antagonist for the study of neuropathic system disorders such as Alzheimer's disease (AD) and schizophrenia.

Galanthamine hydrobromide (Galantamine hydrobromide), a long-acting and centrally active AChE inhibitor (IC50:410 nM), is an allosteric potentiator at neuronal nicotinic ACh receptors.

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.

Anserine (L-Anserine) is a dipeptide containing β-alanine and histidine, which can be found in the skeletal muscle and brain of mammals and birds. Anserine is not cleaved by serum carnosinase and act as biochemical buffers, chelators, antioxidants, and anti-glycation agents. Anserine improves memory functions in Alzheimer's disease (AD)-model mice.

Phosphorylethanolamine (O-Phosphorylethanolamine) is a phosphomonoester metabolite of the phospholipid metabolism. Phosphorylethanolamine is a precursor of phospholipid synthesis and a product of phospholipid breakdown. Phosphomonoesters are present at much higher levels in the brain than in other organs. In developing the brain, phosphomonoesters are normally elevated during the period of neuritic proliferation. This also coincides with the occurrence of normal programmed cell death and synaptic pruning in developing the brain. These findings are consistent with the role of phosphomonoesters in membrane biosynthesis. Phosphorylethanolamine shows a strong structural similarity to the inhibitory neurotransmitter, GABA, and the GABAB receptor partial agonist, 3-amino-propylphosphonic acid. Phosphorylethanolamine is a phosphomonoester which is decreased in post-mortem Alzheimer's disease (AD) brain.

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.

GNE-0723 is a selective positive allosteric modulator of the NMDA receptor, with an EC50 of 21 nM for GluN2A. It can cross the blood-brain barrier (BBB) and improve outcomes in Dravet syndrome (DS) and Alzheimer's disease (AD).

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.

Neuropeptide Y (29-64), amide, human acetate is involved in Alzheimer's disease (AD) and protects rat cortical neurons against β-Amyloid toxicity.

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

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

ABCA1 inducer 1, a non-lipid inducer of ABCA1, enhances ABCA1 expression in E3/4FAD mice expressing human APOE 3/4, augments the lipidation of apolipoprotein (APOE), and reverses various Alzheimer's disease (AD) phenotypes without increasing triglycerides.

HDAC6-IN-50 (Compound 4) is an effective inhibitor of HDAC6 with an IC50 value of 35 nM. It is utilized in the study of Parkinson's disease (PD) and Alzheimer's disease (AD).

BChE-IN-35 (Azo-9) is an inhibitor of BChE. This compound exhibits dynamic cis/trans conformational changes, with the cis isomer preferentially binding to BChE. Additionally, BChE-IN-35 can be utilized in research on Alzheimer's disease (AD).

[11C]MeS-IMPY exhibits a higher binding affinity for β-amyloid plaques extracted from Alzheimer's disease (AD) brains or AD brain homogenates than IMPY, with Ki values of 7.93 nM and 8.95 nM, respectively. [11C]MeS-IMPY is a potential radioactive ligand for positron emission tomography (PET) imaging of β-amyloid plaques.

Simufilamum (also known as PTI-125) is an oral small-molecule compound candidate that targets altered conformations of filamin A. It binds and reverts the misfolded filamin A in the brains of Alzheimer's disease patients, thereby slowing the disease's pathological progression. Additionally, PTI-125 reduces tau protein hyperphosphorylation, decreases Aβ42 aggregation and deposition, neurofibrillary tangles, and neuroinflammation. The compound demonstrates concentration-dependent efficacy in vitro, starting at 1 picomolar (pM), in both control groups and post-mortem hippocampal slices from Alzheimer's disease (AD) patients. PTI-125 is the first therapeutic candidate to preferentially bind and reverse pathogenic protein conformations.

ChAT IN-1 is a selective inhibitor of Choline Acetyltransferase (ChAT) that is utilized in studying mechanisms related to non-neuronal ChAT overexpression in cancers such as colon cancer and lung cancer, as well as in research concerning Alzheimer's disease (AD).

MS8511 hydrochloride is a selective G9a/GLP inhibitor with IC50 values of 100 nM and 140 nM respectively, exhibiting covalent and irreversible characteristics. MS8511 reduces intracellular H3K9me2 levels and enhances anti-proliferative activity, making it suitable for investigating multiple cancers.

GSK-3β inhibitor24 (Compound 41) is a potent GSK-3β inhibitor with an IC50 of 0.22 nM. It increases GSK-3β phosphorylation at the Ser9 site in a dose-dependent manner and inhibits tau protein hyperphosphorylation by reducing the abundance of p-tau-Ser396. The compound upregulates β-catenin and neurogenesis-related markers (GAP43 and MAP-2), demonstrating significant anti-Alzheimer's disease (AD) activity.

AChE/MAO-B-IN-7 (VAV-8) is a compound that acts as a dual inhibitor of acetylcholinesterase (AChE) and MAO-B, with the ability to cross the blood-brain barrier. It also inhibits the aggregation of Aβ42, making it a valuable compound for Alzheimer's disease (AD) research.