neurodegenerative disorders

VBIT-4 is a voltage-dependent anion channel 1 (VDAC1) oligomerization inhibitor (Kd: 17 μM). VBIT-4 can be used for therapeutic purposes in apoptosis-associated disorders (such as neurodegenerative and cardiovascular diseases).

1. Berberine (Umbellatine) is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism. 2. Berberine may as a broad-spectrum anti-microbial medicine, a complementary therapeutic agent for HIV/AIDS. 3. Berberine seems to act as an herbal antidepressant and a neuroprotector against neurodegenerative disorders. 4. Berberine is used in histology for staining heparin in mast cells. As a natural dye, berberine has a colour index of 7516. 5. Berberine reduces hepatic fat content in rats with nonalcoholic fatty liver disease; also prevents proliferation of hepatic stellate cells (HSCs), which are central for the development of fibrosis during liver injury. 6. Berberine can ameliorate proinflammatory cytokines-induced intestinal epithelial tight junction damage in vitro, and berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states. 7. Berberine has antineoplastic effects, including breast cancer, leukemia, melanoma, epidermoid carcinoma, hepatoma, pancreatic cancer, oral carcinoma, tongue carcinoma, glioblastoma, prostate carcinoma and gastric carcinoma, etc.

GSK-239512 is an antagonist of H3 receptor and can be used in studies about the treatment of cognitive dysfunction in neurodegenerative disorders.

AKOS037652256 can be used as a TRPML modulator for the treatment of diseases associated with TRPML activity such as lysosomal accumulation disorders, muscular dystrophy, common age-related neurodegenerative diseases, oxidative stress or reactive oxygen species (ROS)-related diseases and ageing.

5-[(1S,2S)-2-[(Cyclopropylmethyl)amino]cyclopropyl]-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide hydrochloride is a cyclopropanoid enzyme compound that acts as a lysine-specific demethylase-1 inhibitor for schizophrenia, developmental disorders, and neurodegenerative diseases.

Fluparoxan hydrochloride is a highly selective and potent α2-adrenoceptor antagonist for the prevention, amelioration or treatment of neurodevelopmental disorders and neurodegenerative diseases.

(3aR,9aR)-Fluparoxan is a highly selective and potent adrenergic receptor α2B antagonist for the prevention, amelioration or treatment of neurodevelopmental disorders and neurodegenerative diseases.

Sinbaglustat (OGT2378) (OGT2378) is a dual inhibitor of glucose ceramide synthetase (GCS) and non-lysosomal glucose ceramidase (GBA2).Sinbaglustat is an orally administered N-alkyl iminosugar that crosses the blood-brain barrier.Sinbaglustat is used for the treatment of lysosomal storage disorders and for the study of central neurodegenerative disorders associated with lysosomal dysfunction. Sinbaglustat is used for the treatment of lysosomal storage disorders and for the study of lysosomal dysfunction-related central neurodegenerative diseases.

ZT-1a is a SPAK inhibitor.ZT-1a inhibits SPAK.ZT-1a can be used for the prevention and treatment of neurodegenerative and neurocognitive disorders.

SSR180711 hydrochloride (SSR-180711A HCl) is a selective Alpha7 nicotinic acetylcholine partial agonist for the study of neurodegenerative and cognitive disorders.

Dehydronitrosonisoldipine is an inhibitor of sterile α and TIR motif-containing 1 and can be used in studies about neurodegenerative disorders. Dehydronitrosonisoldipine inhibits axon degenration and the Vincristine-activated cADPR production in neurons.

Pifithrin-β hydrobromide (Cyclic PFT-α) is an inhibitor of p53; reversibly blocks p53-dependent transcriptional activation and apoptosis. Protects against neuronal death in models of stroke and neurodegenerative disorders. Active in vivo; protects mice from the side-effects of Y therapy associated with p53 induction. Supresses self-renewal of embryonic stem cells. Also aryl hydrocarbon receptor (AHR) agonist, causes upregulation of AHR target gene CYP1A1 (EC50 = 1.1 μM).

Didymin (Neoponcirin) has antioxidant property. Didymin induces apoptosis by inhibiting N-Myc and upregulating RKIP in neuroblastoma, may used for neuroblastoma therapy. Didymin may be a potential therapeutic molecule for the treatment of neurodegenerative disorders associated with oxidative stress.

BCATc Inhibitor 2 exhibited an IC50 of 0.8 microM in the hBCATc assays; it is an active and selective inhibitor. BCATc Inhibitor 2 also blocked calcium influx into neuronal cells following inhibition of glutamate uptake, and demonstrated neuroprotective e

Sirtuin modulator 2 (N-(3-(imidazo[2,1-b]thiazol-6-yl)phenyl)-2-methoxybenzamide) exhibits antidiabetic, anti-inflammatory and antitumor activities.

COH1 is a ribonucleotide reductase (RR) inhibitor utilized in research pertaining to cancer, mitochondrial diseases, and neurodegenerative disorders [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].

Ganglioside GM2 asialo (asialo- GM2) is a glycosphingolipid containing three monosaccharide residues and a fatty acid of variable chain length but lacking the sialic acid residue present on ganglioside M2. Asialo-GM2 levels are low-to-undetectable in normal human brain, but it accumulates in the brain of patients with Tay-Sachs and Sandhoff disease, which are neurodegenerative disorders characterized by deficiency of lysosomal β-hexosaminidase A and B, respectively. It also binds to various bacteria, including Pseudomonas isolates derived from cystic fibrosis patients. Asialo-GM2 mixture contains ganglioside GM2 asialo molecular species with fatty acyl chains of variable lengths.

MIF-IN-1 (compound 14) is a potent inhibitor of macrophage migration inhibitory factor (MIF) with a pIC50 of 6.87, targeting a proinflammatory cytokine linked to various diseases, including neurodegenerative disorders [1].

Verdiperstat (AZD 3241) is a selective, irreversible and orally active myeloperoxidase inhibitor, with an IC50 of 630 nM, and can be used in the research of neurodegenerative brain disorders.

BRD3731 is a selective inhibitor of GSK3β, demonstrating an IC50 value of 15 nM for GSK3β and 215 nM for GSK3α. Due to its inhibitory properties, BRD3731 holds promise for investigating various medical conditions, including post-traumatic stress disorder (PTSD), psychiatric disorders, diabetes, and neurodegenerative disorders [1].

SUCNR1-IN-2 (Statement 35) inhibits both succinate and succinate receptor 1, and is used in research related to neurodegenerative disorders, including neuroinflammation [1].

AA147 (ATF6-activator-147) is a small molecule endoplasmic reticulum (ER) proteostasis regulator. The selectively activates ATF6 arm of the unfolded protein response (UPR) .It acts as a prodrug that preferentially triggers ATF6 signaling through a mechanism involving localized metabolic activation and selective covalent modification of ER resident proteins that regulate ATF6 activity.

1. Tiliroside (Tribuloside) shows anticarcinogenic activity. 2. Tiliroside shows hepatoprotective activity. 3. Tiliroside shows antioxidant and anti-inflammatory activity, can inhibit neuroinflammation in neurodegenerative disorders. 4. Tiliroside has anti-diabetic effect, are at least partially mediated through inhibitory effects on carbohydrate digestion and glucose uptake in the gastrointestinal tract. 5. Tiliroside and gnaphaliin are antioxidants against in vitro Cu(2+)-induced LDL oxidation in the same order of magnitude compared to that of the reference drug, probucol. 6. Tiliroside enhances fatty acid oxidation via the enhancement adiponectin signaling associated with the activation of both AMP-activated protein kinase and peroxisome proliferator-activated receptor α and ameliorates obesity-induced metabolic disorders.

Dizocilpine Maleate (MK 801) is a potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) with Kd of 37.2 nM in rat brain membranes. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role.

C-ABL-IN-2 is a highly effective inhibitor of the c-Abl protein, which plays a significant role in the development of several diseases, including cancer. This compound exhibits promise for investigating neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), as well as cancer. (Source: WO2020260871A1, compound 25) [1].

Sirtuin Modulator 4, a sirtuin modulator, exhibits an inhibitory effect on SIRT1, presenting an EC 50 value ranging from 51-100 μM. It is potentially useful in research aimed at prolonging cell lifespan and preventing a broad spectrum of diseases and disorders such as diabetes, obesity, neurodegenerative, cardiovascular diseases, inflammation, and cancer.

THX-B, a potent non-peptidic antagonist of the neurotrophin receptor p75 (p75 NTR), is utilized in the study of diabetic kidney disease, neurodegenerative, and inflammatory disorders [1] [2] [3].

Pyridazinediones-derivative-1 shows potential in the treatment of neurodegenerative disorders.

Z-Phe-Ala-diazomethylketone directly binds to Aβ42 monomers and small oligomers, inhibiting Aβ42 dodecamer formation and preventing Aβ42 fibrillogenesis in solution. This compound holds potential for research into neurodegenerative disorders [1].

A-971432 is a sphingosine-1-phosphate receptor 5 (S1P5) agonist that is selective for S1P5 over S1P1 and S1P3 (IC50s = 0.006, 0.362, and >10 µM, respectively). It inhibits forskolin-induced cAMP production in CHO cells expressing S1P5 (EC50 = 4.1 nM). A-971432 (1 µM) increases electrical resistance of hCMEC/D3 cells in an in vitro blood-brain barrier model, indicating enhanced barrier integrity, and attenuates blood-brain barrier leakage in an R6/2 transgenic mouse model of Huntington’s disease when administered at a dose of 0.1 mg/kg.[1] [2] A-971432 (0.1 mg/kg per day, i.p.) decreases the number of errors made in a horizontal ladder task and increases latency to fall in the rotarod test in R6/2 mice. It also increases spontaneous alternation in the t-maze in aged mice when administered at a dose of 0.1 mg/kg.[1] References [1].Hobson, A.D., Harris, C.M., van der Kam, E.L., et al. Discovery of A-971432, an orally bioavailable selective sphingosine-1-phosphate receptor 5 (S1P5) agonist for the potential treatment of neurodegenerative disorders. J. Med. Chem. 58(23), 9154-9170 (2015).[2]. Di Pardo, A., Castaldo, S., Amico, E., et al. Stimulation of S1PR5 with A-971432, a selective agonist, preserves blood-brain barrier integrity and exerts therapeutic effect in an animal model of Huntington’s disease. Hum. Mol. Genet. 27(14), 2490-2501 (2018).

PF-06648671 is a γ-secretase modulator for the treatment of neurodegenerative and/or neurological disorders.

VBIT-3 is a voltage-dependent anion channel 1 (VDAC1) oligomerization inhibitor (Kd: 31.3 μM). VBIT-3 also is an apoptosis inhibitor, can be used for therapeutic purposes in apoptosis-associated disorders (such as neurodegenerative and cardiovascular diseases).

Dyrk1A-IN-3 (Compound 8b) is a highly selective inhibitor of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) with a high binding affinity (IC50 of 76 nM). Dyrk1A-IN-3 can be used in neurodegenerative disorders research, such as Alzheimer’s Disease, Huntington’s Disease, and Parkinson’s Disease [1].

UWA-101 hydrochloride is a selective, non-cytotoxic inhibitor of DAT/SERT, demonstrating EC50 values of 3.6 µM for DAT and 2.3 µM for SERT inhibition. It mitigates motor disorders and other side effects associated with dopaminergic agent use (e.g., L-DOPA) without exhibiting psychotropic effects. This compound is utilized in research focused on neurodegenerative conditions like Parkinson's disease [1] [2].

Ph-HTBA, a high-affinity, brain-penetrating modulator for CaMKIIα, exhibits a binding affinity with a Kd value of 757 nM. It holds potential for use in research related to ischemia and neurodegenerative disorders.

Rolofylline (KW-3902) is a selective adenosine A1 receptor antagonist utilized in research on acute congestive heart failure, renal dysfunction, and neurodegenerative disorders.

IL-17A modulator-2, exhibits inhibitory properties towards IL-17A, with a pIC50 of 8.3. Its effectiveness lies in attenuating the biological effects associated with IL-17A activity. IL-17A modulator-2 finds utility in the study of diseases and disorders characterized by dysregulated IL-17A modulation, such as those involving immune dysfunction, autoimmune pathology, cancer, and neurodegenerative conditions.

Inonophenol C functions as a neurotrophic agent, offering protection against neurodegenerative disorders.

WAY-215718 is an active molecule. It is a potent and selective serotonin 5-HT6 receptor antagonist, exhibiting significant efficacy in targeting cognitive impairment and memory enhancement [5HT6]. Its pharmacological profile includes high binding affinity and specificity to the 5-HT6 receptor, making it a promising candidate for therapeutic use in neurodegenerative diseases and psychiatric disorders.

NSC363998 (free base), an orally active compound, suppresses rCGG90-induced neurotoxicity and is utilized in researching neurodegenerative disorders, including Fragile X associated tremor/ataxia syndrome (FXTAS) [1].

Nesuparib (JPI-547/OCN-201) is a potent PARP inhibitor with inhibitory effects on PARP and TNKS1.Nesuparib has antitumor activity and can be used in the treatment of tumors, endocrine and metabolic disorders, genitourinary disorders, and can be used in the study of neuropathic pain, neurodegenerative disorders, and cardiovascular diseases.

Calpain Inhibitor XI, a reversible covalent inhibitor of calpain-1, is utilized in the research of neurodegenerative disorders.

CypD-IN-3, a potent and subtype-selective cyclophilin D (CypD) inhibitor, exhibits a high affinity for CypD with an IC50 value of 0.01 μM. It is applicable in the research of various conditions, such as oxidative stress, neurodegenerative disorders, liver diseases, aging, autophagy, and diabetes [1].

CypD-IN-4 is a potent, subtype-selective cyclophilin D (CypD) inhibitor exhibiting a high affinity for CypD with an IC50 value of 0.057 μM. This compound is utilized in the research of various diseases, such as oxidative stress, neurodegenerative disorders, liver diseases, aging, autophagy, and diabetes [1].

O-GlcNAcase-IN-4 is an inhibitor of O-GlcNAcase. It holds potential for researching neurodegenerative diseases and disorders, including Alzheimer's disease [1].

Member of the neurotrophin growth factor family that binds and activates TrkB and p75 neurotrophin receptors. Enhances the survival, growth and differentiation of neurons. BDNF expression is altered in neurodegenerative disorders such as Parkinson's and A

Sirtuin Modulator 5, a sirtuin modulating agent, activates SIRT1 with an efficacy marked by a DC50 value of less than 50 μM. It is applicable in enhancing cell longevity and is researched for its therapeutic potential in a wide range of diseases such as those associated with aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular diseases, blood clotting disorders, inflammation, cancer, and flushing. Furthermore, it holds promise for conditions that could benefit from boosted mitochondrial activity [1].

HDAC-IN-58, a selective HDAC6 inhibitor, exhibits potent inhibitory activity with an IC50 of 2.06 nM, rendering it suitable for research into chronic neurodegenerative and psychiatric disorders [1].

ASN90 is a specific, orally active inhibitor of the O-GlcNAcase (OGA) enzyme, demonstrating an IC50 of 10.2 nM. It is utilized in the research of neurodegenerative disorders including tauopathies and α-synucleinopathies [1].