PMX-205 is a cyclic hexapeptide that acts as a potent antagonist of C5a receptor (C5aR; IC50= 31 nM).1It is orally active and blocks inflammatory signaling and symptoms in animal models of colitis and allergic asthma.2,3PMX-205 is also brain penetrant and reduces neuroinflammation and neurodegeneration in an animal model of Alzheimer's disease.4 1.March, D.R., Proctor, L.M., Stoermer, M.J., et al.Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes. Relationships between structures and activityMol. Pharmacol.65(4)868-879(2004) 2.Jain, U., Woodruff, T.M., and Stadnyk, A.W.The C5a receptor antagonist PMX205 ameliorates experimentally induced colitis associated with increased IL-4 and IL-10Br. J. Pharmacol.168(2)488-501(2013) 3.Staab, E.B., Sanderson, S.D., Wells, S.M., et al.Treatment with the C5a receptor/CD88 antagonist PMX205 reduces inflammation in a murine model of allergic asthmaInt. Immunopharmacol.21(2)293-300(2014) 4.Fonseca, M.I., Ager, R.R., Chu, S.-H., et al.Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's diseaseJ. Immunol.183(2)1375-1383(2009)
Kynurenic acid, an active metabolite of tryptophan, is synthesized through a kynurenine intermediate by kynurenine aminotransferases (KATs). It acts as an antagonist of both NMDA and AMPA receptors, as well as α7 nicotinic acetylcholine receptors (nAChRs; EC50s = 235, 101, and 7 µM, respectively), and functions as an agonist for the aryl hydrocarbon receptor (AhR) and G protein-coupled receptor 35 (GPR35; EC50s = 1.4 and 39 µM, respectively). In a neonatal rat model of cerebral hypoxic-ischemia, induced by carotid artery ligation, administration of kynurenic acid at 300 mg kg prevents weight loss in the lesioned hemisphere. Additionally, at concentrations of 1 and 5 mg ml, it protects against neurodegeneration in the rhabdomere of the eye in an Htt93QtransgenicDrosophila model of Huntington's disease. Elevated levels of kynurenic acid in the cerebrospinal fluid have been observed in patients with schizophrenia.
C-ABL-IN-1 is a new and specific inhibitor of the c-Abl protein, which effectively prevents the progression of neurodegeneration observed in Parkinson's disease.
Rocaglaol is a potent anticancer drug that induces apoptosis of LNCaP cells through the mitochondrial pathway and its G2 M-phase cell cycle arrest is associated with the down-regulation of Cdc25C and the dephosphorylation of Cdc2. Rocaglaol can reduce tis
Arachidoyl ethanolamide, a saturated fatty acyl ethanolamide lacking classical (CB1 CB2) activity, plays a role in a complex system comprising central cannabinoid (CB1), peripheral cannabinoid (CB2), and non-CB receptor-mediated pharmacology. This system has paved the way for extensive research in diverse fields such as memory, weight loss and appetite, neurodegeneration, tumor surveillance, analgesia, and inflammation. Unlike other compounds, Arachidoyl ethanolamide does not bind to the murine CB1 receptor nor does it compete with anandamide for the fatty acid amide hydrolase, the endocannabinoid hydrolytic enzyme. The non-CB receptor-mediated actions of saturated ethanolamides like Arachidoyl ethanolamide are currently under investigation.
Ezeprogind (AZP-2006) is an orally active neurotrophic inducer that effectively addresses the underlying factors contributing to neurodegeneration, with a broad scope extending beyond the conventional targets like Abeta protein and tau protein. Exhibiting potent neuroprotective properties, Ezeprogind is a valuable tool for studying a range of neurological disorders, including progressive supranuclear palsy (PSP), tauopathies, Alzheimer's disease, Parkinson's disease, and others.
C2-8 is an inhibitor of polyglutamine (polyQ) aggregation (IC50s = 25 and 0.05 μM for recombinant HDQ51 and in PC12 cells, respectively). It also inhibits polyQ aggregation in organotypic hippocampal slice cultures isolated from R6 2 transgenic mice and reduces neurodegeneration in a dose-dependent manner in a Drosophila model of Huntington's disease. C2-8 (100 and 200 mg kg) reduces huntingtin aggregate size, reduces neuronal atrophy, and improves motor performance in a rotarod test in the R6 2 transgenic mouse model of Huntington's disease.
DOPAL is an aldehyde product of the oxidative deamination of dopamine by monoamine oxidase.[1] It can be further oxidized to 3,4-dihydroxyphenylacetic acid (DOPAC) by aldehyde dehydrogenase (ALDH) and, to a lesser extent reduced to 3,4-dihydroxyphenyl ethanol (DOPET). DOPAL is toxic to neurons.[2],[3] It can also oligomerize and precipitate α-synuclein, an event associated with Parkinson's disease.[2] Mice lacking cytosolic and mitochondrial forms of ALDH display increased levels of DOPAL as well as neurodegeneration and motor dysfunction characteristic of Parkinson’s disease.[4]