spatial

Bucladesine sodium (DC2797) is a cAMP analog with cell-permeable properties. Bucladesine sodium is also a cAMP-dependent protein kinase (PKA) activator and a phosphodiester (PDE) inhibitor. Bucladesine sodium has anti-inflammatory activity.

SB 202190 (FHPI) is a p38 MAPK inhibitor that inhibits p38α and p38β2 (IC50=50 100 nM) selectively and cell-permeably. SB 202190 has antitumor activity and also induces the differentiation of human embryonic stem cells into cardiomyocytes.

Androsta-1,4,6-triene-3,17-dione is a lipophilic and specific aromatase inhibitor (Ki: 0.18 μM) that inhibits estrogen biosynthesis, exhibits antifertility effects, and induces impairment of spatial memory.

Ginsenoside Rg1 (Panaxoside Rg1) is a class of steroid glycosides, and triterpene saponins found exclusively in the plant genus Panax (ginseng). It improves spatial learning and increase hippocampal synaptophysin level in mice, plus demonstrates estrogen-like activity.

3-Aminopropyltriethoxysilane (APTES) immobilizes biomolecules on silicon-based materials, such as Si3N4, while acting as a spacer to provide spatial freedom and higher activity for immobilized biomolecules to build analytical platforms for biosensing, recognition and more.

Amylose is a polysaccharide composed of α-D-glucose units linked by α(1→4) glycosidic bonds, accounting for about 20% of the total amount of starch. Amylose spatial conformation curls into a helix and forms a blue complex with iodine, which is widely used in the food industry, and can be used in a variety of researches as a natural product and a biochemical reagent.

H-89 is a selective and potent protein kinase A inhibitor (IC50: 48 nM), a candidate cardioprotectant, induces spatial learning impairment in rats, and can be used to study myocardial infarction.

RMC-6291 is an orally active, covalent inhibitor of KRAS G12C (ON) that forms a tri-complex within tumor cells between KRAS G12C (ON) and cyclophilin A (CypA), thereby preventing KRAS G12C (ON) from signaling via steric blockade of RAS effector binding and eliciting deep and durable suppression of RAS pathway activity in KRAS G12C tumor models [1].

ZIP acetate is a novel, cell-permeable inhibitor of protein kinase Mζ (PKMζ), a constitutively active, atypical PKC isozyme involved in LTP maintenance. Selectively blocks PKMζ-induced synaptic potentiation in hippocampal slices in vitro. Reverses late-ph

(S)-MCPG ((+)-MCPG) is a class I II metabotropic glutamate receptors (mGluRs) antagonist that blocks spatial learning and long-term enhancement of the dentate gyrus in vivo in rats, and can be used to study neurological disorders.

Adekalant (also known as H 345 52) is an innovative antiarrhythmic compound characterized by minimal proarrhythmic activity. It blocks HERG-mediated currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC50) of 230 nM. Adekalant binds preferentially to open channels and exhibits rapid kinetic behavior, being trapped when channels close. Its voltage-independent properties have been observed during square pulse and action potential clamp protocols. Research suggests that delaying the repolarization of human cardiac muscle through I(Kr) blockage is the primary mechanism of Adekalant’s action. It effectively blocks I(Kr) while having relatively low efficacy in blocking I(Ca), delaying ventricular repolarization without significantly increasing temporal or spatial dispersion and without inducing early afterdepolarizations or torsades de pointes (TdP).

AChE BChE-IN-25 (Compound 6e) is an orally active inhibitor of hAChE and eqBChE, with IC50 values of 7.9 nM and 0.79 nM, respectively. This compound exhibits antioxidant activity, effective in scavenging free radicals with an IC50 of 22.91 μM. AChE BChE-IN-25 demonstrates neuroprotective effects by reducing mitochondrial and cellular oxidative stress in a Drosophila Alzheimer's model and improves spatial and cognitive memory impairments induced by Scopolamine in mouse models.

hAChE hBuChE-IN-1 (compound C2) acts as a dual inhibitor of cholinesterases, exhibiting IC50 values of 514 nM for hAChE and 358 nM for hBuChE. It is orally active and capable of enhancing cognitive function and spatial memory.

CGP 35348 is a selective antagonist of GABAB receptor (EC50 = 34 μM). CGP 35348 can be used in studies of neuromuscular coordination and spatial learning after neonatal brain damage in albino mice.

Notch signaling pathway activator; enhances the self-renewal capability of neural stem cells (NSCs) via Notch signaling pathway activation in vitro and in vivo. Promotes the expression of Notch target genes, Hes3 and Hes5. Expands the NSCs pool and promotes endogenous neurogenesis in the hippocampal dentate gyrus (DG) after chronic administration in mice. Increases the spatial and episodic memory in mice.

Guanfacine-13C,15N3is intended for us as an internal standard for the quantification of guanfacine by GC- or LC-MS. Guanfacine is an α2-adrenergic receptor (α2-AR) agonist with Kivalues of 93, 1,380, and 3,890 nM for α2A-, α2B-, and α2C-ARs, respectively, in a radioligand binding assay.1It has EC50values of 52, 288, and 602 nM for α2A-, α2B-, and α2C-ARs, respectively, for stimulated [35S]GTPγS binding. It also binds to imidazoline receptor 1 (Ki= 19 nM in a radioligand binding assay).2Guanfacine (0.3-5 mg/kg) binds to adrenergic receptors in the central nervous system and lowers blood pressure in hypertensive rats in a dose-dependent manner.3It also improves spatial working memory deficits induced by hypobaric hypoxia in rats.4Formulations containing guanfacine are used in the treatment of high blood pressure and attention deficit hyperactivity disorder (ADHD). 1.Jasper, J.R., Lesnick, J.D., Chang, L.K., et al.Ligand efficacy and potency at recombinant α2 adrenergic receptors: Agonist-mediated [35S]GTPγS bindingBiochem. Pharmacol.55(7)1035-1043(1998) 2.Nikolic, K., Filipic, S., and Agbaba, D.QSAR study of imidazoline antihypertensive drugsBioorg. Med. Chem.16(15)7134-7140(2008) 3.Scholtysik, G.Pharmacology of guanfacineBr. J. Clin. Pharmacol.10(Suppl 1)21S-24S(1980) 4.Kauser, H., Sahu, S., Kumar, S., et al.Guanfacine is an effective countermeasure for hypobaric hypoxia-induced cognitive declineNeuroscience254110-119(2013)

para-amino-Blebbistatin is a more water-soluble form of (S)-4'-nitro-blebbistatin , which is a more stable and less phototoxic form of (-)-blebbistatin .1,2,3 (-)-Blebbistatin is a selective cell-permeable inhibitor of non-muscle myosin II ATPases that rapidly and reversibly inhibits Mg-ATPase activity and in vitro motility of non-muscle myosin IIA and IIB for several species (IC50s = 0.5-5 μM), while poorly inhibiting smooth muscle myosin (IC50 = 80 μM).2,3,4 Through these effects, it blocks apoptosis-related bleb formation, directed cell migration, and cytokinesis in vertebrate cells. However, prolonged exposure to blue light (450-490 nm) results in degradation of blebbistatin to an inactive product via cytotoxic intermediates, which may be problematic for its use in fluorescent live cell imaging applications.5,6 The addition of a 4'-amino group increases its water solubility, decreases the inherent fluorescence, stabilizes the molecule to circumvent its degradation by prolonged blue light exposure, and decreases its phototoxicity while retaining the in vitro and in vivo activity of blebbistatin.7 para-amino-Blebbistatin has the same stereochemistry as the active (-)-blebbistatin enantiomer. |1. Várkuti, B.H., Képiró, M., Horváth, I.á., et al. A highly soluble, non-phototoxic, non-fluorescent blebbistatin derivative. Sci. Rep. 6:26141, (2016).|2. Straight, A.F., Cheung, A., Limouze, J., et al. Dissecting temporal and spatial control of cytokinesis with a myosin II inhibitor. Science 299(5613), 1743-1747 (2003).|3. Kovács, M., Tóth, J., Hetényi, C., et al. Mechanism of blebbistatin inhibition of myosin II. J. Biol. Chem. 279(34), 35557-35563 (2004).|4. Limouze, J., Straight, A.F., Mitchison, T., et al. Specificity of blebbistatin, an inhibitor of myosin II. J. Muscle Res. Cell Motil. 25(4-5), 337-341 (2004).|5. Kolega, J. Phototoxicity and photoinactivation of blebbistatin in UV and visible light. Biochem. Biophys. Res. Commun. 320(3), 1020-1025 (2004).|6. Sakamoto, T., Limouze, J., Combs, C.A., et al. Blebbistatin, a myosin II inhibitor, is photoinactivated by blue light. Biochemistry 44(2), 584-588 (2005).|7. Verhasselt, S., Roman, B.I., Bracke, M.E., et al. Improved synthesis and comparative analysis of the tool properties of new and existing D-ring modified (S)-blebbistatin analogs. Eur. J. Med. Chem. 136, 85-103 (2017).

Negative control for st-Ht31 . Gorshkov et al (2017) AKAP-mediated feedback control of cAMP gradients in developing hippocampal neurons. Nat.Chem.Biol. 13 425 PMID:28192412 |Vijayaraghavan et al (1997) Protein kinase A-anchoring inhibitor peptides arrest mammalian sperm motility. J.Biol.Chem. 272 4747 PMID:9030527 |Vincent et al (2017) Signaling: Spatial regulation of axonal cAMP. Nat.Chem.Biol. 13 348 PMID:28328917

Amyloid-β (1-42) (Aβ42) is a neurotoxic 42-amino acid protein fragment found in amyloid plaques in postmortem cerebral cortex from patients with Alzheimer's disease.1,2,3Aggregation of Aβ42 results in the formation of neurotoxic fibrils or globular oligomers.1Aβ42 accumulates in the brain of many transgenic mouse models of Alzheimer's disease and, in many models, the onset of amyloid deposition positively correlates with deficits in spatial learning and memory.4 1.Wolfe, M.S.Therapeutic strategies for Alzheimer's diseaseNat. Rev. Drug Discov.1(11)859-866(2002) 2.Iwatsubo, T., Odaka, A., Suzuki, N., et al.Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ42(43)Neuron13(1)45-53(1994) 3.Hardy, J.A., and Higgins, G.A.Alzheimer's disease: The amyloid cascade hypothesisScience256(5054)184-185(1992) 4.Jankowsky, J.L., and Zheng, H.Practical considerations for choosing a mouse model of Alzheimer's diseaseMol. Neurodegener.12(1)89(2017)

ω-Hydroxy-DEET, a significant metabolite of the insect repellent N-N-diethyl-meta-toluamide (DEET), exhibits anti-proliferative properties. DEET, renowned for being a spatial repellent and irritant, is frequently employed to deter mosquito contact.

Yhhu-3792 activates Notch signaling pathway and promotes the expression of Hes3 and Hes5. Yhhu-3792 enhanced the self-renewal ability of neural stem cells (NSCs), expanded the NSC pool and promoted endogenous neurogenesis in the dentate gyrus (DG) of the hippocampus in mice. Yhhu-3792 can improve the situational and spatial memory ability of mice. Yhhu-3792 has research potential in DG dysfunction related to memory impairment.

CY208-243 is a D1 agonist. CY208-243 attenuates the pattern electroretinogram to low spatial frequency stimuli in the monkey. CY208-243 stimulates adenylate cyclase in rat striatal homogenates with an EC50 of 125 nM. CY208,243 was superior in improving the strength of neuronal outcome sensitivity to the working memory-related choice behavior in the T-maze.

Artemisinin B is a drug which may improve spatial memory in dementia patients and alter the levels of inflammatory cytokines in the hippocampus and the cortex. Artemisinin B may inhibit neuroinflammation and exert neuroprotective effects on cognitive functions by modulating the TLR4-MyD88-NF-κB signaling pathway. Artemisinin B has shown potential in the treatment of neuroinflammatory diseases.

Nrf2 Activator-8 (Compound 10e), with an EC50 of 37.9 nM, is a potent Nrf2 activator that demonstrates significant antioxidant and anti-inflammatory properties in BV-2 microglial cells. Furthermore, this compound notably ameliorates spatial memory deficits in a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation [1].