MAR2011 Neuroscience Products: Inhibitors, Substrates, Agonists, and Antagonists

Cayman offers a select group of research tools (inhibitors and substrates as well as receptor agonists and antagonists) pertinent to Neuroscience research areas such as Alzheimer’s disease and pain management as well as more general factors related to excitatory and inhibitory signal transduction.

Item No. Product Name Notes

78050 (-)-(α)-Kainic Acid Developed as the prototype neuroexcitatory amino acid for the induction of seizures in experimental animals 13644 Aspalatone Generates antioxidant and neuroprotective effects against kainic acid-induced epilepsy in rat hippocampus 10008346 Gabapentin A GABA analog

13623 Topiramate A sugar sulfamate that exhibits potent anticonvulsant activity

13667 Muscimol A full GABAA agonist and partial GABAC agonist

10032 N-(α-Linolenoyl) Tyrosine A simple a-amide conjugate prepared as a method for CNS dopamine content by facilitated transport of the tyrosine precursor across the blood-brain barrier 13248 L-DOPA A metabolic precursor of dopamine that is capable of crossing the blood-brain barrier

13205 Halopemide A potent inhibitor of phospholipase D and dopamine receptors

10488 Bupropion (hydrochloride) An inhibitor of dopamine and norepinephrine reuptake and an antagonist of neuronal acetylcholine nicotinic receptors 13358 CAY10608 A potent, selective, and non-competitive antagonist of the NR2B subunit of NMDA receptors

10010743 (technical grade) The primary active component of the heat and pain-eliciting lipid-soluble fraction of the Capsicum pepper 92350 Capsaicin The primary active component of the heat and pain-eliciting lipid-soluble fraction of the Capsicum pepper 92355 A major impurity found in natural hot pepper extracts

90052 Arvanil A structural analog of capsaicin

90262 Olvanil A structural analog of capsaicin

10005633 CAY10448 A potent capsaicin receptor antagonist

10007518 A competitive antagonist of TRPV1

To view Cayman’s entire line 10009501 20-hydroxy A potential CYP450 metabolite of N-arachidonoyl taurine that may activate N-Arachidonoyl Taurine members of the TRP family of calcium channels of Neuroscience products, 10012565 CAY10568 A physically smaller, less hydrophobic version of QX314 designed to be more permeable to TRPV1 request a copy of the 10137 Icilin A synthetic CMR1/TRPM8 super agonist that serves as a reference cold nociceptive Neuroscience catalog agonist for TRP-type ion channels 70090 BW 723C86 A 5-HT receptor agonist with 10-fold selectivity for the HT2B receptor

13203 Agomelatine A metabolically stable analog of melatonin a competitive antagonist of 5-HT2C and 5-HT2B receptors 10011546 AL 34662 A potent 5-HT2 receptor agonist with ocular hypotensive activity

10096 SB 242084 (hydrochloride) An antagonist of the 5-HT2C receptor

10005254 AFMK A melatonin metabolite that has antioxidant and free radical scavenging activities

90377 13-Docosenamide The amide of docosenoic acid identified in the CSF of sleep-deprived cats

10012588 A-803467 A sodium channel blocker with high-affinity and selectivity for inhibiting human Nav1.8 sodium channels 10009312 SKF-96365 (hydrochloride) Inhibits the receptor-mediated influx of calciumvia voltage-gated calcium channels

10010109 8-DY547-cGMP A fluorescently-labeled cyclic nucleotide used to study CNGA2 channel activation

10011135 BAY-60-7550 A potent type 2 cyclic nucleotide phosphodiesterases (PDE2) inhibitor

10011126 Clobenpropit (hydrobromide) A selective histamine H3 receptor antagonist that crosses the blood-brain barrier

10011127 Thioperamide Maleate A selective histamine H3 receptor antagonist that crosses the blood-brain barrier

9000849 Phenazepam A benzodiazepine agonist of the GABAA-benzodiazepine receptor chloride channel complex

For full information on these products and more, visit caymanchem.com Alzheimer’s Disease Methyltransferase Activity Methylation of key biological molecules and proteins play important roles in numerous Insoluble deposits of β-amyloid peptide (Aβ) and hyperphosphorylation biological systems. S-adenosylmethionine (SAM) dependent methyltransferases use SAM, of the microtubule-associated tau protein leads to the aggregation and also known as AdoMet, to donate a methyl group that is required for the modification of formation of amyloid plaques and neurofibrillary tangles, both hallmarks proteins and DNA. Aberrant levels of SAM have been linked to many abnormalities, including Alzheimer’s disease, depression, Parkinson’s disease, multiple sclerosis, liver failure, and cancer. of Alzheimer’s disease. In an effort to support the necessary research to prevent and treat the symptoms of this degenerative disease, Cayman Methyltransferase Fluorometric Assay Kit 700150

offers a collection of tools that target the inhibition of β-amyloid peptide Cayman’s Methyltransferase Fluorometric Assay Kit 14,000 production and aggregation, as well as the prevention of tau protein is an enzyme-coupled assay that can continuously 12,000 10,000 phosphorylation and modification. Additional compounds purport to stave monitor SAM-dependent methyltransferases. The e Units) 8,000 removal of the methyl group from SAM generates elativ off dementia and improve cognitive function by targeting other various 6,000

S-adenosylhomocysteine (AdoHcy), which is rapidly escence (R 4,000

signaling pathways. Fluor converted to S-ribosylhomocysteine and adenine 2,000

by AdoHcy nucleosidase. This rapid conversion 0 0 10 20 30 40 b-Amyloid prevents the buildup of AdoHcy and its feedback Time (min) Theβ -amyloid peptide is derived from sequential proteolytic cleavage of the amyloid precursor inhibition on the methylation reaction. Finally, the adenine is converted to hypoxanthine, protein (APP) by β- and γ-secretases. Initial cleavage by β-secretase (BACE), a membrane by adenine deaminase, which in turn is converted to urate and (H2O2). anchored aspartic protease, generates a soluble N-terminal fragment and a membrane-associated The reaction between H2O2 and ADHP (10-acetyl-3,7,-dihydroxyphenoxazine) produces C-terminal fragment. The C-terminal fragment then undergoes proteolysis byγ -secretase to the highly fluorescent compound resorufin. Resorufin fluorescence can be easily analyzed give the Aβ peptide. with an excitation wavelength of 530-540 nm and an emission wavelength of 585-595 nm.

β-Amyloid (1-8, A2V) Peptide 10229 Methyltransferase Colorometric Assay Kit 700140 Cayman’s Methyltransferase Colorimetric Assay 0.450 Aβ, Aβ 1-8 mutant, β-amyloid (1-8) dominant negative 0.400 β-Amyloid peptide (1-42) aggregation results in the formation of neurotoxic fibrils or globular Kit operates on a similar principle as the above 0.350 0.300 673 → 673 fluorometric kit except the rate of production of 5 nm) oligomers. The amyloid precursor protein (APP) mutation Ala Val results in disease for 0.250 homozygous carriers but not for heterozygous carriers. The mutation generatesβ -amyloid peptide H2O2 is measured with the colorimetric reagent, 0.200 0.150 with valine at amino acid position two. Biochemical analysis of Aβ (1-42) aggregation suggests 3,5-dichloro-2-hydroxybenzenesulfonic acid, by an Absorbance (51 increase in absorbance at 500-520 nm. 0.100 this small peptide may be a useful guide for developing β-amyloid peptide aggregation inhibitors. 0.050 0.000 0 5 10 15 20 25 30 35 • Also Available: b-Amyloid (1-8) Peptide (10241) Time (min)

BACE (human recombinant) 10227 ASP-2, BACE-1, Memapsin, Membrane-bound Aspartic Protease, b-Secretase Methionine Sulfoxide Purity: ≥95% Summary: Source: human recombinant C-terminal His-tag protein purified Protein methionine sulfoxide (MetO) is a reversible oxidative modification that occurs by from E. coli • Mr: 48 kDa exposure of protein(s) methionine residues to reactive oxygen species (ROS). Methionine oxidation can alter the function(s) of the modified proteins and if not reversed by MetO BACE Inhibitor Screening Assay Kit 600070 reductases can be further oxidized to methionine sulfone, an irreversible modification. The overabundance of methionine sulfoxidation is implicated in age-related diseases. BACE, the major β-secretase, initiates the 120 first step inβ -amyloid peptide production. 100 Inhibition of BACE activity could potentially 80 Methionine Sulfoxide Immunoblotting Kit 600160

60 ctivity

block the entire cascade of Alzheimer’s disease A Cayman’s MetO Immunoblotting Kit contains reagents needed for the immunochemical pathogenesis. Cayman’s BACE Inhibitor 40 detection of proteins containing MetO residues by western blotting. MetO-containing % Initial Screening Assay Kit provides a convenient 20 samples of interest include those from cell or tissue lysates as well as semi-pure or purified method for screening human BACE inhibitors. 0 proteins. Samples may be prepared with reducing or non-reducing sample buffer prior -20 The assay utilizes a synthetic Swedish mutant APP 0 10 100 1,000 to SDS-PAGE and tested alongside one SDS-PAGE well designated for the provided peptide (EVNLDAEF) that has been linked to a Inhibitor (nM) positive control. The MetO Polyclonal Antibody was isolated from rabbit serum generated fluorophore (EDANS) at one end and to a quenching agent (Dabcyl) at the other. After after immunization with a oxidized corn protein (MetO-DZS18) rich in methionine. cleavage by BACE, the product (peptide-EDANS) is brightly fluorescent and can be easily This polyclonal antibody is specific for protein methionine sulfoxide and can detect IgG- analyzed using a fluorescence plate reader or a fluorometer with excitation wavelengths of containing MetO from sera of Alzheimer’s patients but not from normal control sera. 335-345 nm and emission wavelengths of 485-510 nm. Additional Compounds

Item No. Product Name Notes

13332 (S)-Glycyl-H-1152 (hydrochloride) A selective, potent Rho kinase IV inhibitor derived from HA-1077 (Fasudil)

70240 Tacrine (hydrochloride) A derivative of aminoacridine which functions as an inhibitor of both AChE and butyrylcholinesterase 10005836 bis(7)-Tacrine An AChE inhibitor that is 1,000 times more potent than tacrine 13245 Donepezil A reversible AChE inhibitor that readily crosses the blood-brain barrier to reduce the breakdown of acetylcholine 13662 Arecoline (hydrobromide) An agonist of the muscarinic acetylcholine receptors M1, M2, and M3 10230 (+)-Muscarine (iodide salt) The biologically active stereoisomer of muscarine A non-selective antihistamine that also inhibits the neurotoxic action of β-amyloid and blocking L-type calcium channels, inhibits NMDA-type 9000556 Dimebolin glutamate receptors, and prevents mitochondrial leakage 10011349 Dimebolin (hydrochloride) The hydrochloride form of Dimebolin soluble in both aqueous and organic solvents 13197 DAPT An inhibitor of γ-secretase; blocks production of total Aβ in human primary neuronal cultures 10007963 E-64 A natural, potent, and irreversible inhibitor of cysteine proteases

10009021 AVE-1625 A highly potent, selective antagonist for the CB1 receptor; significantly improves the performance of rodents in working memory tasks An inhibitor of histone deacetylases and GSK3 that depletes cellular inositol-1,4,5-trisphosphate; shows promise in combination therapy for 13033 Valproic Acid (sodium salt) cancer and in treating Alzheimer’s disease

MAR2011 Cayman Chemical Ann Arbor, MI (800) 364-9897 caymanchem.com