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.

BRD4097, a negative control in the HDAC1/2/3/8 assay, is a selective histone deacetylase (HDAC3) inhibitor that can be used to protect b-cells and improve insulin resistance, help promote cognitive function and enhance learning and memory formation.

GGTI 2147 FA, a selective GGT inhibitor, abolishes bicuculline-induced increase in dendritic spine density in hippocampal experiments and may reduce learning and memory abilities in mice.

Uridine-3'-monophosphate is a nucleoside used in the biochemical synthesis of ribothymidine-3'-phosphate. It has been used as a bioavailable source of uridine in research studies designed to enhance learning and memory.

Betamethasone 21-phosphate is a synthetic glucocorticoid.1It prevents increases in macrophage and eosinophil numbers in bronchoalveolar lavage fluid (BALF) and decreases in blood leukocyte numbers in a guinea pig model of parainfluenza-3 viral infection when administered at a dose of 8 mg/kg but does not prevent airway hyperresponsiveness after infection.2Betamethasone 21-phosphate inhibits cell infiltration into the aqueous humor in a rat model of endotoxin-induced uveitis when administered topically or subcutaneously at doses of 0.01-1% or 1 mg/kg, respectively.3It increases maximal lung pressure volume curves in fetal sheep when administered to pregnant ewes at 0.75 gestation at doses of 80 and 170 μg/kg.1Betamethasone 21-phosphate increases body weight, impairs learning and memory, increases anxiolytic behavior, and reduces hippocampal neurogenesis in CD-1 mice but reduces body weight and increases neurogenesis with no effect on anxiety in high-anxiety DBA/2 mice when administered at a dose of approximately 25 mg/kg per day in the drinking water for seven weeks.4Formulations containing betamethasone 12-phosphate and betamethasone acetate have been used in the treatment of severe allergic conditions and a variety of immune-related conditions. 1.Loehle, M., Schwab, M., Kadner, S., et al.Dose-response effects of betamethasone on maturation of the fetal sheep lungAm. J. Obstet. Gynecol.202(2)186.e181-186.e187(2010) 2.Leusink-Muis, A., Ten Broeke, R., Folkerts, G., et al.Betamethasone prevents virus-induced airway inflammation but not airway hyperresponsiveness in guinea pigsClin. Exp. Allergy29(Suppl. 2)82-85(1999) 3.Tsuji, F., Sawa, K., Kato, M., et al.The effects of betamethasone derivatives on endotoxin-induced uveitis in ratExp. Eye Res.64(1)31-36(1997) 4.Aiello, R., Crupi, R., Leo, A., et al.Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesisBehav. Brain Res.278155-166(2015)

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.

2-Deoxy-D-galactose, a glucose analog, impedes glycolysis, thereby inhibiting tumor growth, and interferes with fucosylation of glycomacromolecules, which impairs memory consolidation in learning tasks. Additionally, this compound hinders the fucosylation of glycoproteins in vivo [1].

Unifiram is a nootropic agent.1It increases acetylcholine (ACh) release in the rat cerebral cortexin vivoand induces a long-lasting increase in the amplitude of field excitatory postsynaptic potentials (fEPSPs) in the rat hippocampal CA1 region (EC50= 27 nM). It does not bind to serotonin (5-HT), dopamine, muscarinic, nicotinic, adrenergic, glutamate, histamine, opioid, or GABA receptors at 1 μM. Unifiram (0.1 mg/kg) improves memory in non-memory-impaired rats in a social learning test.2It also prevents memory deficits induced by the anticholinergic agent scopolamine, nicotinic receptor antagonist mecamylamine, GABABreceptor agonist baclofen, or α2-adrenergic receptor agonist clonidine in the passive avoidance test in mice when administered at a dose of 0.01 mg/kg and prevents memory deficits induced by the AMPA/kainate glutamate receptor antagonist NBQX at 0.1 mg/kg.1 1.Romanelli, M.N., Galeotti, N., Ghelardini, C., et al.Pharmacological characterization of DM232 (unifiram) and DM235 (sunifiram), new potent cognition enhancersCNS Drug Rev.12(1)39-52(2006) 2.Ghelardini, C., Galeotti, N., Gualtieri, F., et al.The novel nootropic compound DM232 (unifiram) ameliorates memory impairment in mice and ratsDrug Develop. Res.56(1)23-32(2002)

BChE-IN-4 is a highly potent inhibitor of the enzyme butyrylcholinesterase, capable of crossing the blood-brain barrier. It effectively reduces learning and memory impairments resulting from a deficiency in cholinergic activity in a mouse model. BChE-IN-4 holds promise for further investigation in the field of Alzheimer's disease research [1].

DL-AP7, a competitive NMDA antagonist and anticonvulsant, blocks NMDA-induced convulsions and impairs learning performance in mice during a passive avoidance task [1].

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.

LZWL02003, an anti-neuroinflammatory agent, demonstrates a protective effect on MPP+-induced neuronal damage and reduces ROS expression. Additionally, it enhances cognition, memory, learning, and athleticism in Rotenone-induced Parkinson's disease (PD) rat models, suggesting its potential for neurodegenerative disease research [1].

delta-Valerobetaine is a diet-dependent obesogen, a microbiome-derived metabolite, and a precursor of trimethylamine N-oxide (TMAO). delta-Valerobetaine is deleterious to learning and memory processes in mice, and can modulate inhibitory synaptic transmission and neuronal network activity.

Positive allosteric modulator of AMPA receptors (pEC50 = 5.2 for potentiation of AMPA-mediated currents in vitro). Also potentiates AMPA-mediated synaptic responses in vivo. Improves performance of rats in various learning and memory paradigms Ward et al (2010) Discovery of N-[(2S)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide, a novel clinical AMPA receptor positive modulator. J.Med.Chem. 53 5801 PMID:20614889 |Ward et al (2017) Pharmacological characterization of N-[(2S)-5-(6-fluoro-3-pyridinyl)-2, 3-dihydro-1H-inden-2-yl]-2-propanesulfonamide: a novel, clinical AMPA receptor positive allosteric modulator. Br.J.Pharmacol. 174 370 PMID:28009436

SSTR4 agonist 4 is a potent SSTR4 agonist that has the potential for the pain research. SSTR4 agonists are effective in rodent models of pain associated with acute and chronic associated anti-peripheral nociceptive and anti-inflammatory activity. SSTR4 is expressed at relatively high levels in the hippocampus and neocortex, regions of memory and learning, and in Alzheimer's disease pathology [1].

SSTR4 agonist 3 is a potent compound that activates the SSTR4 receptor. The SSTR4 receptor is highly expressed in the hippocampus and neocortex, which are regions associated with memory, learning, and Alzheimer's disease pathology. SSTR4 agonists demonstrate strong efficacy in rodent models of pain, both acute and chronic, by reducing peripheral nociception and inflammation. Considering its potential application in pain research, SSTR4 agonist 3 is of interest[1].

Octopamine hydrochloride ((±)-p-Octopamine hydrochlorid) is a biogenic monoamine structurally associated with noradrenaline. It can serve as a neurohormone, a neurotransmitter, and a neuromodulator in invertebrates.

ZSET1446 (ST-101) is a T-type calcium channel activator potentially for the treatment of learning deficits in various types of Alzheimer disease (AD) models.

(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.

Yhhu-3792 hydrochloride is a compound that bolsters the self-renewal capacity of neural stem cells (NSCs), catalyzes the Notch signaling pathway, and upregulates expression of Hes3 and Hes5. It augments the NSC pool, stimulates endogenous neurogenesis in the mouse hippocampal dentate gyrus (DG), and enhances mice's spatial and episodic memory skills. This compound shows promise for researching learning and memory impairments linked to DG dysfunction [1].

Paeoniflorin (Peoniflorin) is a herbal constituent extracted from the root of Paeonia albiflora Pall.

AR-R17779 hydrochloride is a potent, selective full agonist of the nAChR, demonstrating K i values of 92 nM for the α7 subtype and 16,000 nM for the α4β2 subtype. It is noted for its ability to enhance learning and memory in rats, suggesting potential therapeutic applications. Additionally, this compound exhibits anxiolytic properties and can mitigate inflammation by activating anti-inflammatory cholinergic (vagal) pathways [1] [2] [4].

Duartin is an anti-rickettsial compound. These small molecules and the workflow, featuring a high-throughput phenotypic screen for growth inhibitors of intracellular Rickettsia spp. and machine learning models for the prediction of growth inhibition of an obligate intracellular Gram-negative bacterium, should prove useful in the search for new therapeutic strategies to treat infections from Rickettsia spp. and other obligate intracellular bacteria.

BRD4884 is a selective inhibitor of HDAC2 that acts by enhancing the learning and memory processes.

KDS2010 is a potent, highly selective, and reversible MAO-B inhibitor which shows 12,500-fold selectivity over MAO-A. KDS2010 overcomes the disadvantages of the irreversible MAO-B inhibitor and significantly attenuates increased astrocytic GABA levels and astrogliosis, thereby enhancing synaptic transmission, and rescuing learning and memory impairments in APP/PS1 mice.

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)

[DPro5] Corticotropin Releasing Factor, human, rat, a selective R2 agonist of corticotropin-releasing factor/hormone (CRF), is a hypothalamic hormone that prompts the release of adrenocorticotropic hormone (ACTH) and β-endorphin. Unlike typical agents, it does not induce anxiogenic effects but instead influences learning and memory processes in rats [1].

Aftin-4, an amyloid forty-two inducer, activates γ-secretase, promoting the generation of amyloid-β-1-42 (Aβ1-42) from amyloid-β protein precursor. Aftin-4(Aftin4) increased Aβ-1-42, but not Aβ-1-40 in mouse hipppocampus, accompanied by learning deficits and mitochondrial ultrastructural changes similar to those found in the brains of patients with AD. Aftin-4(Aftin4) can thus be used to induce a rapid, acute Alzheimer's disease-like toxicity in the rodent brain.

BRD6688 is a selective HDAC2 inhibitor that acts by enhancing the learning and memory processes

PF-04449613 is a phosphodiesterase 9A (PDE9A) inhibitor (IC50= 22 nM).1It is selective for PDE9A over PDE1C (IC50= >1,000 nM), as well as over a variety of other PDEs, inhibiting PDE2-8, -10, and -11 activity by less than 30% in a panel of enzymes, ion channels, and transporters at 1 μM but does inhibit the human dopamine transporter (DAT; Ki= 293 nM). PF-04449613 (0.1-100 mg/kg, s.c.) increases cerebrospinal fluid (CSF) levels of cyclic GMP (cGMP) in rats. Subcutaneous administration of PF-04449613 (10 mg/kg) increases the rate of dendritic spine formation and elimination in mouse primary motor cortex pyramidal neuronsin vivo.2It increases the average running speed of mice in an accelerating rotarod task, indicating improved motor learning, at the same dose. 1.Claffey, M.M., Helal, C.J., Verhoest, P.R., et al.Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitorsJ. Med. Chem.55(21)9055-9068(2012) 2.Lai, B., Li, M., Hu, A., et al.The phosphodiesterase 9 inhibitor PF-04449613 promotes dendritic spine formation and performance improvement after motor learningDev. Neurobiol.78(9)859-872(2018)

Amyloid-β (25-35) (Aβ (25-35)) is an 11-residue fragment of the Aβ protein that retains the physical and biological characteristics of the full length peptide. It forms fibrils that react to thioflavin T and Congo red and are organized in a cross-β arrangement of β-strands similar to Aβ (1-40) and Aβ (1-42) fibrils. Aggregated Aβ (25-35) decreases the viability of rat adrenal PC12 cells. It also decreases the viability of primary rat cortical neurons at concentrations ranging from 1 nM to 30 μM. In vivo, intracerebral injection of Aβ (25-35) (20 nmol) in rats induces lesions of neuronal and tissue loss. Aggregated Aβ (25-35) administered intracerebroventricularly to rats induces learning and memory impairments in the Y-maze, novel object recognition, and contextual fear conditioning tests.

Calpain-2-IN-1 is a selective calpain-2 inhibitor that prolongs ERK activation and thus enhances learning and memory.

Ponezumab (PF-04360365), a humanized anti-amyloid IgG2 monoclonal antibody, effectively lowers Aβ levels in the central nervous system and enhances learning and memory performance in mouse models. It holds potential for Alzheimer's disease research [1].

Tebuconazole is an agricultural azole fungicide. It can also inhibit CYP51 (IC50s: 0.9 and 1.3 μM for Candida albicans CYP51 and truncated Homo sapiens CYP51, respectively).