amyotrophic

β-N-Methylamino-L-alanine hydrochloride (L-BMAA hydrochloride) is a neurotoxin produced by cyanobacteria that may contribute to the development of amyotrophic lateral sclerosis (ALS) and possibly other neurodegenerative diseases.

NF-κΒ Activator 2 is a potent, orally active compound that efficiently activates NF-κB with an EC50 value of 1.58 μM. By enhancing NF-κB expression and activation, it induces SOD 2 synthesis, rendering it useful for amyotrophic lateral sclerosis (ALS) research [1].

Tauroursodeoxycholate (UR 906), also known as ursodoxicoltaurine, is a highly hydrophilic tertiary bile acid that is produced in humans at a low concentration. Tauroursodeoxycholate is the more hydrophilic form of ursodeoxycholic acid, which is the more abundant naturally produced bile acid in humans.Tauroursodeoxycholate is being investigated for use in several conditions such as Primary Biliary Cirrhosis (PBC), insulin resistance, amyloidosis, Cystic Fibrosis, Cholestasis, and Amyotrophic Lateral Sclerosis.

(2R,3S)-N-(4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-4H-1,2,4-triazol-3-yl)-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide is an Apelin receptor agonist with an EC50 for Apelin receptors of 0.012 µM.(2R,3S)-N-(4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-4H-1,2,4-triazol-3-yl)-3-(5- methylpyrimidin-2-yl)butane-2-sulfonamide is used in the treatment of heart failure, atherosclerosis, obesity, diabetes mellitus, amyotrophic lateral sclerosis, coronary artery disease, hypertension, stroke and myocardial infarction.

Utreloxastat (PTC857) is a novel 15-lipoxygenase inhibitor that can be used to study amyotrophic lateral sclerosis .

DNL343 is a selective and potent eIF2B activator that crosses the blood-brain barrier and inhibits the assembly of stress granules (SGs) induced by the C9ORF72 dipeptide repeats. DNL343 may be useful in the study of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS).

Riluzole (RP-54274) is a glutamate antagonist (RECEPTORS, GLUTAMATE) used as an anticonvulsant (ANTICONVULSANTS) and to prolong the survival of patients with AMYOTROPHIC LATERAL SCLEROSIS.

EPI-589, a quinone derivative and oxidoreductase enzyme inhibitor, is considered safe and well tolerated, showing promise for the treatment of amyotrophic lateral sclerosis (ALS).

G923-0271 is a TDP-43 inhibitor that improves disease phenotypes in TDP-43 nematode models and reduces the overexpression of human TDP-43 at the cellular level, making it useful for studying diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Arimoclomol (BRX-220 free base), a co-inducer of heat shock proteins (HSP), is utilized in studies on the treatment of amyotrophic lateral sclerosis (ALS).

MAP4K4-IN-6 (Compound 15f) is a MAP4K4 inhibitor with an IC50 of 80 nM. It reduces the phosphorylation of c-Jun and exhibits neuroprotective effects. Additionally, MAP4K4-IN-6 enhances the vitality of motor neurons and can be utilized in the study of amyotrophic lateral sclerosis (ALS).

BSc5367 is a potent inhibitor of the structural domain of Nek1 kinase with an IC50=11.5 nM. Nek1 is a NIMA-associated protein kinase tightly linked to cell cycle regulation, DNA repair, and microtubule regulation. BSc5367 can be used in studies related to amyotrophic lateral sclerosis (ALS), polycystic kidney disease (PKD), and several types of radiotherapy-resistant cancers.

GDC-0134, a dual leucine zipper kinase (DLK) inhibitor, exhibits brain penetration properties. It inhibits DLK to prevent neuronal degeneration and block JNK activation, potentially treating amyotrophic lateral sclerosis (ALS). It has been assessed in a phase 1 study aimed at treating ALS patients.

AKV-9 is an inhibitor of mutant Cu/Zn superoxide dismutase (SOD1), effectively preventing SOD1-induced protein aggregation and providing protection against SOD1-induced cytotoxicity in PC-12 cells, with an EC50 of 0.3 μM. Additionally, AKV-9 has been shown to improve amyotrophic lateral sclerosis (ALS) in mouse models and extend their lifespan.

BNN27 is an agonist of the TrkA receptor (TrkAreceptor) and the p75NTR receptor (p75NTR receptor), exhibiting neurotrophic and anti-apoptotic properties. It enhances levels of glutamate, GABA, and glutamine in the hippocampus and prefrontal cortex of rats, improving glutamate turnover. In a mouse model of amyotrophic lateral sclerosis (ALS), BNN27 demonstrates neuroprotective effects, shows anti-inflammatory properties in an experimental autoimmune encephalomyelitis (EAE) model, and exhibits retinal protection in a rat diabetes model. BNN27 also possesses blood-brain barrier permeability.

MP-010 is an FKBP12 ligand that regulates cytosolic calcium by stabilizing RyR channel activity. It facilitates functional improvement in SOD1G93A mice with amyotrophic lateral sclerosis (ALS), evidenced by enhanced motor coordination, increased integrity of neuromuscular junctions, and significantly higher spinal motor neuron survival rates. MP-010 is applicable for research in the field of neurological disorders.

AIM4 is a compound known for inhibiting TDP-43 aggregation. It demonstrates good biocompatibility and anti-inflammatory activity, making it a valuable agent in research for diseases such as amyotrophic lateral sclerosis (ALS).

SARM1-IN-4 (Compound 7) is an orally active SARM1 inhibitor that reduces plasma neurofilament light chain (NfL) levels in a mouse model following a 50 mg/kg oral dose. By inhibiting the NAD+ hydrolase activity of SARM1, it prevents programmed axon degeneration, making it useful for research in neurodegenerative and neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and peripheral neuropathy.

SARM1-IN-5 (compound 1-23-a) is an inhibitor of SARM1, useful for researching diseases related to axonal degeneration, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS).

RNA binder 1 (Compound 4b) is an RNA-binding agent capable of crossing the blood-brain barrier. It selectively binds to the G-quadruplex structure of the G4C2 repeat sequence RNA of the C9orf72 gene. This compound significantly reduces levels of the toxic polypeptides poly(GA) and poly(GP) in cells derived from amyotrophic lateral sclerosis (ALS) patients, while it has no significant impact on the antisense polypeptide poly(PR), demonstrating selectivity for sense RNA. RNA binder 1 is useful for studying ALS and frontotemporal dementia (FTD).

GM-604(alirinetide) is a potential treatment for amyotrophic lateral sclerosis and ischemic stroke.

WN1316 is a unique neuroprotectant against oxidative injury, being a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS).

The metallo-protein Cu/Zn-superoxide dismutase (SOD1) is a ubiquitous enzyme responsible for scavenging superoxide radicals. Mutations in SOD1, which alter its metal binding capacity and can result in protein misfolding and aggregation, have been linked to familial amyotrophic lateral sclerosis (ALS). Cu-ATSM is an orally bioavailable, blood-brain barrier permeable complex that has traditionally been used in cellular imaging experiments to selectively label hypoxic tissue via its susceptibility to reduction by oxygen-depleted mitochondria. More recently, Cu-ATSM has been reported to improve locomotor function and survival in a transgenic ALS mouse model by delivering copper specifically to cells in the spinal cords of mice producing misfolded SOD1 proteins. Copper chaperone for SOD (CCS) is presumed to utilize the copper from Cu-ATSM to prevent misfolding of the SOD1 protein.

1-Stearoyl-2-docosahexaenoyl-sn-glycero-3-PC is a phospholipid in biological membranes containing stearic acid and docosahexaenoic acid at the sn-1 and sn-2 positions, respectively. It has been used to study the organization and dynamics of lipid membranes. In the superoxide dismutase 1 mutant transgenic mouse model of amyotrophic lateral sclerosis (ALS) 1-Stearoyl-2-docosahexaenoyl-sn-glycero-3-PC levels decrease in the anterior horn of L5 in late stages of the disease.1-Stearoyl-2-docosahexaenoyl-sn-glycero-3-PC can be used to study biological membranes.