SAR502250 is a potent, selective, ATP competitive, orally active and brain-penetrant inhibitor of GSK3, with an IC50 of 12 nM for human GSK-3β. SAR502250 displays antidepressant-like activity. SAR502250 can be used for the research of Alzheimer’s disease (AD)[1][2]. SAR502250 (0.01-1 μM; 36 h) attenuates the Aβ25-35-induced cell death in rat embryonic hippocampal neurons[2]. SAR502250 (1-100 mg kg; a single p.o,) attenuates tau hyperphosphorylation in the cortex and spinal cord of transgenic mice expressing P301L tau[2].SAR502250 (10-30 mg kg; p.o. once daily for 7 weeks) improves the cognitive deficit in transgenic APP(SW) Tau(VLW) mice after infusion of Aβ25-35[2].SAR502250 (10-30 mg kg; a single p.o.) significantly increases the percentage of lever-presses in the inter-response time (IRT) bin (49-96 s), with a significant augmentation of the percentage of reinforced responses[2].SAR502250 (30 mg kg; i.p. once daily for 28 d) ameliorates chronic stress-induced degradation of the physical state of the mice coat[2].SAR502250 (10-60 mg kg; a single p.o.) decreases hyperactivity produced by psychostimulantsin mice[2]. [1]. Fukunaga K, et, al. 2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; a new class of potent, selective and orally active glycogen synthase kinase-3β inhibitors. Bioorg Med Chem Lett. 2013 Dec 15;23(24):6933-7.[2]. Griebel G, et, al. The selective GSK3 inhibitor, SAR502250, displays neuroprotective activity and attenuates behavioral impairments in models of neuropsychiatric symptoms of Alzheimer’s disease in rodents. Sci Rep. 2019 Dec 2;9(1):18045.
16F16 is a protein disulfide isomerase (PDI) inhibitor.1It inhibits PDI reductase activity in an enzyme assay when used at concentrations ranging from 1 to 100 μg/ml.116F16 reduces PC12 cell apoptosis induced by the misfolded huntingtin protein HTTQ103. It suppresses PDI-dependent mitochondrial outer membrane permeabilization (MOMP) in isolated PC12 cell mitochondria. 16F16 (2, 3, 4, and 10 μM) reduces HTTN90Q73mutant huntingtin-induced medium spinal neuron death and MOMP in rat corticostriatal slices. It also reduces pyramidal neuron death induced by amyloid-β precursor protein (APP) in rat corticostriatal slices. 1.Hoffstrom, B.G., Kaplan, A., Letso, R., et al.Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteinsNat. Chem. Biol.6(12)900-906(2010)
Rasagiline-13C3is intended for use as an internal standard for the quantification of rasagiline by GC- or LC-MS. Rasagiline is an inhibitor of monoamine oxidase B (MAO-B; IC50= 4.43 nM for the rat brain enzyme).1It is selective for MAO-B over MAO-A (IC50= 412 nM for the rat brain enzyme). It inhibits serum and NGF withdrawal-induced apoptosis of PC12 cells when used at concentrations ranging from 0.01 to 100 μM.2Rasagiline inhibits rat brain MAO-Bin vivo(ED50= 0.1 mg kg).1It reduces cerebral edema in a mouse model of traumatic brain injury.2Rasagiline (0.1 mg kg) reduces cortical and hippocampal levels of full-length and soluble amyloid precursor protein (APP) in rats and mice. It also reduces α-synuclein-induced substantia nigral neuron loss and improves motor dysfunction in a mouse model of Parkinson's disease.3Formulations containing rasagiline have been used in the treatment of Parkinson's disease. 1.Youdim, M.B.H., Gross, A., and Finberg, J.P.Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase BBrit. J. Pharmacol.132(2)500-506(2001) 2.Youdim, M.B.H., and Weinstock, M.Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug TV3326 [(N-propargyl-(3R) aminoindan-5-YL)-ethyl methyl carbamate]Cell. Mol. Neurobiol.21(6)555-573(2001) 3.Kang, S.S., Ahn, E.H., Zhang, Z., et al.α-Synuclein stimulation of monoamine oxidase-B and legumain protease mediates the pathology of Parkinson's diseaseEMBO J.37(12)e98878(2018)
Amyloid-β (1-8, A2V) is a truncated form of amyloid-β (Aβ) that contains a valine to alanine substitution at position 2 of the Aβ numbering convention (Aβ A2V), which corresponds to position 673 of the amyloid precursor protein (APP) numbering convention (APP A673V). An Aβ (1-40) (Aβ40) A2V peptide increases the production of Aβ and the rate and amount of amyloid fibril formation in vitro, effects that can be reduced by coincubation with wild-type Aβ40. Aβ40 and Aβ42 levels are increased in CHO cells expressing the Aβ A2V mutation and in fibroblasts derived from patients with the Aβ A2V mutation. As a homozygous mutation, Aβ A2V is correlated with Alzheimer's disease with distinctive pathological features, but disease does not develop in patients with a heterozygous Aβ A2V mutation.
Kushenol C is a good 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenger, and it exhibits inhibitory activity against Sodium-dependent glucose cotransporter 2(SGLT2). Kushenol C shows antimicrobial activity against Staphylococcus aureus and Streptococcus mutan