ataxia

Ceralasertib (AZD6738) is an orally active, selective ATR kinase inhibitor with an IC50 of 1 nM.

Elimusertib (BAY-1895344) is a potent, highly selective, and orally available ATR inhibitor with an IC50 of 7 nM, demonstrating significant anti-tumor efficacy as a monotherapy and strong combination potential with targeted alpha therapy Radium-223 dichloride.

Rosolutamide (ALZ-003) is a curcumin analog, an orally active Nrf1 and Nrf2 activator.Rosolutamide modulates oxidative homeostasis, improves mitochondrial function and promotes autophagy, reduces mutant protein aggregation, and decreases intracellular mitochondrial reactive oxygen species (ROS) levels.Rosolutamide has been used in the study of neurodegeneration such as spinal cerebellar ataxia and Huntington disease. neurodegenerative diseases such as Huntington's disease. Regulates oxidative homeostasis.

D-Cysteine, the D-isomer of cysteine, is a powerful inhibitor of E. coli growth and is mediated by D-amino acid oxidase to produce H2S, serving as a neuroprotective agent against cerebellar ataxia. Additionally, D-cysteine can inhibit the growth and cariogenicity of a two-species biofilm formed by Streptococcus mutans and Streptococcus hemoglobin.

Triheptanoin (IND 106011) is a fatty acid metabolic modulator. It potentially for the treatment of fatty acid oxidation disorders and GLUT1.

ETP-46464 is an effective and specific ATR inhibitor (IC50: 25 nM).

KU-55933 (ATM Kinase Inhibitor) is an ATM inhibitor (IC50=12.9 nM; Ki=2.2 nM) that is selective and ATP-competitive. KU-55933 induces apoptosis and has antitumor effects.

1. Sinapine, an alkaloid from seeds of the cruciferous species, can be used as an effective natural compound for chemo-resistance. 2. Sinapine has antioxidant and radio-protective activities.

VE-821 (ATR Inhibitor IV) is a selective ATP competitive inhibitor of ATR( Ki IC50: 13 26 nM in cell-free assays).

AZ32 is an orally bioavailable, blood-brain barrier-penetrating ATM inhibitor with an IC50 of <6.2 nM for the ATM enzyme and an IC50 of 0.31 μM for ATM in cells.

AZD0156 , an effective and specific inhibitors of ATM kinase, is potential antineoplastic activities and chemo- radio-sensitizing.

AChE-IN-27 is a small molecule used for high-throughput assays.

Tuvusertib (M1774) is an orally available ataxia telangiectasia and Rad3-related (ATR) kinase inhibitor (Ki< 1 µΜ) with selective and potentially antitumor activity.Tuvusertib selectively inhibits ATR activity and blocks downstream phosphorylation of serine threonine protein kinase checkpoint kinase 1 (CHK1), thereby inhibits DNA damage checkpoint activation, disrupting DNA damage repair and inducing apoptosis in tumor cells.

NS13001 (N-(4-Chlorophenyl)-2-(3,5-dimethyl-1H-pyrazol-1-yl)-9-methyl-9H-purin-6-amine) is a potent, selective, orally active allosteric positive modulator of SK channels (small conductance calcium-activated potassium channels). The EC50s are 1.8 and 0.14 μM for SK2 and SK3, respectively. NS13001 holds promise as a potential therapeutic agent for treatment of spinocerebellar ataxia type 2 (SCA2) and possibly other cerebellar ataxias.

Troriluzole is an orally active glutamate modulator with anticancer activity.Troriluzole enhances the expression of excitatory amino acid transporters located in glial cells and is used in the study of spinocerebellar ataxia, Alzheimer's disease, and generalized anxiety disorder (GAD).

CGK733 (CGK 733) is a potent and selective inhibitor of ATM ATR.

AZ20 is an effective and specific inhibitor of ATR kinase (IC50: 5 nM, in a cell-free assay), 8-fold selectivity over mTOR.

Dioxabenzofos, a pesticide, could cause reversible ataxia in mice, chicken, and sheep.

Ceralasertib is an orally available inhibitor of ataxia telangiectasia and rad3 related (ATR) kinase. Ceralasertib selectively inhibits ATR activity by blocking the downstream phosphorylation of the serine/threonine protein kinase CHK1. This prevents ATR-

Sinapine Thiocyanate, is a derivative of Sinapine (S486605), an alkaloidal amine found in black mustard seeds. It is the choline ester of Sinapic Acid (S486800). It is also a phenolic-chloine conjugates, acting as anti-oxidants and acetylcholinesterase inhibitors, that can be used for the treatment of Alzheimer's disease (AD).

Potent and selective ATM kinase inhibitor (IC50 = 0.6 nM in an enzyme inhibition assay). Exhibits > 600-fold selectivity for ATM over other kinases. Inhibits ATM kinase in an in vitro cellular assay (IC50 = 0.33 μM). Potentiates the antitumor effects of the topoisomerase 1 inhibitor irinotecan in tumor bearing, immunocompromised mice. Orally bioavailable. Degorce et al (2016) Discovery of novel 3-quinoline carboxamides as potent, selective and orally bioavailable inhibitors of ataxia telangiectasia mutated (ATM) kinase. J.Med.Chem. 59 6281 PMID:27259031

1(R)-(Trifluoromethyl)oleyl alcohol is an analog of oleic acid .1It inhibits ferroptosis induced by erastin in primary fibroblasts isolated from patients with Friedreich ataxia, a neuro- and cardiodegenerative disorder characterized by loss or impaired activity of frataxin (FXN), when used at concentrations of 5, 10, or 20 μM. 1(R)-(Trifluoromethyl)oleyl alcohol (5 μM) reduces lipid peroxidation induced byFXNsiRNA knockdown in NBT human myoblasts. 1.Cotticelli, M.G., Forestieri, R., Xia, S., et al.Identification of a novel oleic acid analog with protective effects in multiple cellular models of Friedreich ataxiaACS Chem. Neurosci.11(17)2535-2542(2020)

Azelaoyl PAF is a potent PPARγ agonist that competitively binds thiazolidinediones with potency comparable to rosiglitazone. In atherosclerosis studies, Azelaoyl PAF promotes the uptake of oxidized low-density lipoprotein (oxLDL) by macrophages by upregulating CD36 expression. In fibroblasts from Friedreich's ataxia (FRDA) patients, Azelaoyl PAF significantly increased mRNA and protein levels of ferritin.

Sinapine hydroxide, an alkaloid derived from the seeds of cruciferous plants, demonstrates a variety of beneficial properties including anti-inflammatory, anti-oxidant, anti-tumor, anti-angiogenic, and radio-protective effects. Additionally, it acts as an inhibitor of acetylcholinesterase (AChE), making it valuable for researching neurodegenerative conditions such as Alzheimer's disease, ataxia, myasthenia gravis, and Parkinson's disease[4].