Amyloid-β Inhibitor

DAPT (GSI-IX) is a potent and orally active γ-secretase inhibitor with IC₅₀s of 115 nM and 200 nM for total amyloid-β (Aβ) and Aβ₄₂, respectively. DAPT inhibits the activation of Notch 1 signaling and induces cell differentiation. DAPT also induces autophagy and apoptosis. DAPT has neuroprotection activity and has the potential for autoimmune and lymphoproliferative diseases, degenerative disease and cancers treatment.

Rolipram is a PDE4 inhibitor, with blood-brain barrier permeability, that reverses β-amyloid-induced learning and memory impairment in rats. Rolipram elevates intracellular cAMP and clevels and regulates the cAMP/CREB signaling pathway, thereby alleviating neuroinflammation and apoptotic responses. Rolipram promotes neuronal differentiation of human bone marrow mesenchymal stem cells and inhibits Methamphetamine- and morphine-induced hyperlocomotion in mice. Rolipram also reduces the viability of glioblastoma stem-like cells and enhances Bevacizumab (HY-P9906)-induced cell death. Rolipram inhibits the expression of proinflammatory cytokines and enhances central noradrenergic transmission. Rolipram is mainly used in studies related to various central nervous system diseases including Alzheimer's disease, major depressive disorder, glioblastoma multiforme, and multiple sclerosis.

Lithium orotate is an orally active lithium supplement with reduced binding that can bypass amyloid sequestration in AD mice models. Lithium orotate can prevent Aβ plaque deposition and phospho-tau accumulation and reverse AD pathology, neuroinflammatory changes and memory loss in AD mice models and ageing wild-type mice. Lithium orotate can be used for the research of alcoholism and Alzheimer’s disease.

Trontinemab (RG6102) is a brain-penetrant, anti-amyloid, bispecific and humanizedized IgG1-κ antibody, targeting to Aβ plaques and transferrin receptor 1 (TFR1). Trontinemab binds to fibrillar Aβ as well as Aβ plaques triggering plaque clearance by engaging immune cells on Alzheimer disease (AD) brain sections. Trontinemab also shows specific affinity to cynomolgus and human TFR1.

FPS-ZM1 is a high-affinity and BBB-permeable RAGE inhibitor with a K_i of 25 nM.

Rutin (Rutoside) is a flavonoid found in many plants and shows a wide range of biological activities including anti-inflammatory, antidiabetic, antioxidant, neuroprotective, nephroprotective, hepatoprotective and reducing Aβ oligomer activities. Rutin is also a CBR1 inhibitor, which can cross the blood brain barrier. Rutin attenuates vancomycin-induced renal tubular cell apoptosis via suppression of apoptosis, mitochondrial dysfunction, and oxidative stress.

Lecanemab (Mouse IgG2a) (Mab158) is a monoclonal antibody that targets soluble β-amyloid and has the potential to reduce cognitive decline. The variable region of Lecanemab (Mouse IGG2a) is consistent with that of Lecanemab, while the constant region is of Mouse IgG2a sequence. Lecanemab (Mouse IgG2a) almost abolishes Aβ accumulation in astrocytes and rescues neurons from Aβ-induced cell death. Lecanemab (Mouse IgG2a) holds promise for research in the field of Alzheimer's disease.

Ginsenoside Rg1 is one of the major active components of Panax ginseng. Ginsenoside Rg1 ameliorates the impaired cognitive function, displays promising effects by reducing cerebral Aβ levels. Ginsenoside Rg1 also reduces NF-κB nuclear translocation.

20(S)-Ginsenoside Rg3 is the main component of Panax ginseng C. A. Meyer. Ginsenoside Rg3 inhibits Na⁺ and hKv1.4 channel with IC₅₀s of 32.2±4.5 and 32.6±2.2 μM, respectively. 20(S)-Ginsenoside Rg3 also inhibits Aβ levels, NF-κB activity, and COX-2 expression.

Pyridoxal phosphate is the active form of vitamin B6, acts as an inhibitor of reverse transcriptases, and is used for the treatment of tardive dyskinesia.

Azeliragon (TTP488) is an orally bioavailable inhibitor of the receptor for advanced glycation end products (RAGE) in development as a potential treatment to slow disease progression with mild Alzheimer’s disease (AD). Azeliragon also can cross the blood-brain barrier (BBB).

Gantenerumab is a fully humanized anti-Aβ IgG1 monoclonal antibody. Gantenerumab can specifically bind to Aβ fibrils and plaques and can be used in Alzheimer's disease research.

Santacruzamate A (CAY-10683, STA) is a potent and selective HDAC2 inhibitor with an IC₅₀ of 119 pM. STA also exerts neuroprotective property against amyloid-β protein fragment 25–35. STA can be used for cancer and neurological disease research.

Cromolyn (Cromoglycate) disodium is an orally active GSK-3β inhibitor with an IC₅₀ of 2.0 μM. Cromolyn disodium is also a mast cell stabilizer that can inhibit the release of mediators from mast cells, regulate reflex bronchoconstriction, and reduce non-specific bronchial hyperreactivity, and Cromolyn disodium can be used in the research of bronchial asthma. In addition, Cromolyn disodium has multiple activities such as anti-inflammatory, anti-allergic, anti-histamine, anti-cancer, and neuroprotective effects.

Aducanumab (BIIB037) is a human monoclonal antibody that selectively targets aggregated amyloid-beta (Aβ). Aducanumab shows blood-brain-barrier penetration, and can be used for Alzheimer's disease (AD) research.

Apomorphine ((-)-Apomorphine) is a potent dopamine receptor agonist. Apomorphine also inhibit MAO-A and MAO-B. Apomorphine exerts neuroprotective effect and can relax rat corpus cavernosum. Apomorphine can inhibit ROS production, DNA fragmentation and inibit JNK and ERK1/2 phosphorylation. Apomorphine can enhance degradation of intracellular Aβ40 and Aβ42, reduces tau protein levels and inhibit MMP-9 expression. Apomorphine is a highly potent radical scavenger and iron chelator. Apomorphine can be used for the researches of dementia, parkinson's disease, alzheimer disease, breast carcinoma, and erectile dysfunction.

Liensinine is a bisbenzylisoquinoline alkaloid. By inhibiting the PI3K/AKT and JNK/p38-MAPK signaling pathways, Liensinine suppresses autophagy and apoptosis, clears Aβ, and exerts anti-inflammatory, antioxidant and neuroprotective effects. Liensinine activates AMPK and inhibits the expression of HIF-1α and VEGF, thereby suppressing angiogenesis. Liensinine exerts anti-tumor effects through ROS-mediated inhibition of the JAK2/STAT3 signaling pathway. Liensinine can be used for the research of diseases such as Alzheimer's disease, hepatocellular carcinoma, osteosarcoma, sepsis-induced organ injury and stroke.

Tolcapone (Ro 40-7592) is a selective, potent and orally active COMT inhibitor with an IC₅₀of 773 nM. Tolcapone can inhibits α-syn and Aβ₄₂ oligomerization and fibrillogenesis. Tolcapone can cause oxidative stress and induce cancer cells apoptosis and ROS production. Tolcapone can be used for the researches of cancer and neurological disease, such as Parkinson disease and neuroblastoma.

Donanemab (LY3002813) is a humanized IgG1 monoclonal antibody directed at an N-terminal pyroglutamate amyloid beta (Aβ) epitope. Donanemab has the potential for early Alzheimer's disease research.

Emrusolmin (Anle138b), an oligomeric aggregation inhibitor, blocks the formation of pathological aggregates of prion protein (PrPSc) and of α-synuclein (α-syn). Emrusolmin strongly inhibits oligomer accumulation, neuronal degeneration, and disease progression in vivo. Emrusolmin has low toxicity and an excellent oral bioavailability and blood-brain-barrier penetration. Emrusolmin blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology.