Neuroscience

NAS-181 is a potent and selective rat 5-hydroxytryptamine 1B (r5-HT1B) antagonist (Ki: 47 nM).NAS-181 enhances the accumulation of 5-HTP in rat brain regions.

AMG-8718, an oral BACE1 blocker (IC50: 0.0007 μM), also inhibits BACE2 (IC50: 0.005 μM), lowering CSF and Aβ40 brain levels.

VU0360172 is a positive allosteric modulator of mGlu5 receptors (EC50 = 16 nM; Ki = 195 nM).

(S)-Bexcaserin (compound 2) serves as a 5-HT2C receptor agonist, presenting research possibilities in obesity and psychiatric disorders [1].

13,14-dihydro-15-keto Prostaglandin E2 (13,14-dihydro-15-keto PGE2) serves as the predominant metabolite of PGE2 in plasma, created through a 15-keto PGE2 intermediate by the action of 15-oxo-PG Δ13 reductase. Unlike its precursor PGE2, this compound exhibits poor binding affinity towards EP2 and EP4 PGE2 receptors (Ki values of 12 and 57 µM, respectively) in CHO cells and fails to stimulate adenylate cyclase activity therein (EC50s >18 and >38 µM, respectively). Concentrations of 13,14-dihydro-15-keto PGE2 are notably higher in the plasma of pregnant women during their third trimester and at labor and delivery stages, whereas its levels are found to be reduced in the tumor tissues of patients with non-small cell lung cancer (NSCLC) compared to adjacent healthy tissue.

TM-10: Potent BuChE inhibitor, IC50 8.9 nM, disaggregates Aβ, antioxidant, BBB penetrant, may treat Alzheimer's.

Rislenemdaz (CERC-301) (CERC-301) is an antagonist of the N-methyl-D-aspartate (NMDA) receptor subunit 2B (GluN2B).

Atabecestat (JNJ-54861911) is an oral BACE1 inhibitor for Alzheimer's treatment with strong brain uptake and lasting PK/PD effects.

Philanthotoxin 74 dihydrochloride is an antagonist of AMPAR with IC50s of 263 and 296 nM for GluR3 and GluR1.

AMPA receptor antagonist-3 is an AMPA receptor antagonist.

Tematropium (CDDD3602) possesses anticholinergic effects and can be used in neurological studies.

R-(+)-EU-1180-453 is a novel GluN2C/D selective NMDAR-positive modulator for the study of neurological disorders.

SB 216641 hydrochloride (SB-216641A) is a 5-HT1B/D receptor antagonist with anxiolytic properties.

γ-Secretase-IN-1 is a γ-secretase inhibitor that displays partial antiproliferative activity against T-47D cells.

Didesmethyl cariprazine, Cariprazine's active metabolite, treats schizophrenia/bipolar with D3/D2 affinity; half-life 1-3 weeks.

TZ3O is an anticholinergic compound with neuroprotective activity.TZ3O ameliorates memory impairment in Scopolamine-induced Alzheimer's type model in rats.

WAY-607695 is a potential 5-HT1A receptor agonist.

VU6004909 is an mGlu5 receptor orthosteric modulator that reverses MK801-induced increased cortical activity and cognitive dysfunction.

Osemozotan is a 5-HT1A receptor agonist potentially for the treatment of generalized anxiety disorder.

PXS-5153A rapidly inhibits lysyl oxidase 2/3 enzymes, blocks activity in 15 mins, and reduces fibrosis.

PXS-5120A is an irreversible fluoroallylamine Lysyl Oxidase-like 2/3 (LOXL2/3) inhibitor with anti-fibrotic activity.

MDR-1339 is a blood-brain-barrier-permeable inhibitor of amyloid-β (Aβ) aggregation.

Lumateperone (ITI 722) is a 5HT2A receptor antagonist and a dopamine receptor phosphoprotein modulator (DPPM).

SB-616234-A is a selective and orally bioavailable antagonist of 5-HT1B receptor, with anxiolytic and antidepressant activity.

PTCA is a potent ligand for Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), with a pKi value of 7.2.

Compound 3e, a potent GABAA agonist, targets GABA sites and has potential anti-depressive effects in mice.

K203 is a potent tabun-inhibited AChE reactivator and is an important antidote to organophosphorus poisoning.

BChE-IN-3: Selective, pseudo-irreversible BChE inhibitor (IC50: 56.9 nM); borderline reversible AChE inhibitor.

LY593093 is a selective partial orthosteric agonist of M1 muscarinic acetylcholine receptor.

PF470 (PF-06297470) is a negative allosteric modulator of the metabotropic glutamate receptor 5 (mGluR5), which demonstrated significant therapeutic effects in Parkinson's disease models. However, its clinical development was halted due to potential issues identified in toxicological studies.

Fletazepam, a benzodiazepine derivative, exhibits sedative, anti-anxiety, and muscle-relaxant properties. It is utilized in neurological research.

SB 224289: selective 5-HT1B antagonist, pKi 8.2, 60x selectivity, effective orally.

5-HT1A antagonist; Ki=8nM, Kb=0.04nM. PDE4B IC50=80.4μM; PDE7A IC50=151.3μM. Good biofilm penetration, stable, anticognitive, antidepressant.

Refisolone is an antagonist of the GABAA receptor.

Designed anti-Alzheimer’s compound; potent Glutaminyl Cyclase inhibitor; IC50 at 4.5 nM; reduces brain Aβ; improves cognition.

Norneostigmine is a potent inhibitor of AChE capable of crossing the blood-brain barrier. When administered to mice, it achieves a 50% inhibition rate of brain AChE activity within 10 minutes, comparable to the effect of Tetrahydroaminoacridine (57% inhibition in 10 minutes). Norneostigmine is applicable in research on Alzheimer's disease and other memory-related disorders.

PF-06442609 is an orally active γ-secretase modulator with an IC50 value of 6 nM for Aβ42. It exhibits good CNS permeability.

CPPG: potent group II/III mGlu receptor antagonist, 20x more selective for group III (IC50: 2.2 nM) than II (46.2 nM) in rat cortex.

LRRK2-IN-6 is an oral, selective LRRK2 inhibitor crossing the blood-brain barrier, targeting GS (IC50: 4.6μM) and WT LRRK2 (IC50: 49μM).

(+)-Cevimeline HCl hemihydrate is a muscarinic agonist for dry mouth in Sjogren's with rapid absorption, differing metabolism in species.

BChE-IN-2, a pyrimidine/pyridine derivative, potently inhibits BChE (Ki 0.099 μM) and shows promise in AD research.

U92016A hydrochloride: potent, orally active 5-HT1A agonist, metabolically stable, high intrinsic activity, Ki=0.2 nM.

AAZ-A 154 hydrochloride is a selective, competitive, non-hallucinogenic antagonist of 5-HT2AR. It promotes neuronal growth in rodents and results in enduring beneficial behavioral effects.

BChE-IN-38 (compound 13) is a potent BChE inhibitor, with Ki values of 62.05, 28.78, 14.09, and 1.15 nM for hCAI, hCAII, AChE, and BChE, respectively. BChE-IN-38 also demonstrates cytotoxic activity.

S-8510 phosphate is an agonist of inverse Benzodiazepine (BDZ) receptor(Kis of 34.6 nM, 36.2 nM for –GABA and +GABA respectively).

BACE-1 Inhibitor 2 is a potent, CNS-permeable inhibitor of BACE-1, exhibiting an IC50 value of 1.5 nM in enzymatic assays [1].

5-HT2A receptor agonist-7 (517) functions as a modulator of the 5-HT2A receptor, with an EC50 value of less than 100 nM.

Compound 22d is a GSM that crosses the blood-brain barrier, inhibits Aβ42 production (IC50: 60 nM), and may help study Alzheimer's.

TDI-11861 is a second-gen sAC (ADCY10) inhibitor with an IC50 of 5.5 nM and slow dissociation.

2002-G12 (compound 5a) is an Aβ42 inhibitor that can reduce Aβ42 toxicity by 76%. It is applicable in Alzheimer's research.

Dual AChE-MAO B-IN-1: orally active CNS-permeable, safe, stable neuroprotective agent; AChE IC50=550 nM, MAO-B IC50=8.2 nM.

AChE-IN-25: selective, potent AChE inhibitor, non-competitive, IC50 = 2.95 μM, for Alzheimer's research.

CL-13 is an inhibitor of butyrylcholinesterase (BChE), exhibiting an IC50 of 1.15 μM and a selectivity index (SI) of 9.2 for acetylcholinesterase. It demonstrates antioxidative activity in SH-SY5Y cells with a DPPHEC50 of 47.01 μM and has the capacity to chelate metals involved in Aβ aggregation and/or oxidative stress, showing no neurotoxicity at concentrations up to 50 μM. CL-13 can also reverse scopolamine-induced cognitive impairments without affecting motor abilities in mice.

LRRK2-IN-3: potent, selective oral LRRK2 blocker, BBB-penetrant, IC50 of 0.6 nM in hPBMCs, for Parkinson's research.

AChE-IN-79 (compound 3i) is an acetylcholinesterase inhibitor with an IC50 of 2.7 µM, suitable for studies related to Alzheimer's disease.

Antioxidant agent-8, an oral Aβ 1-42 inhibitor, reduces fibril aggregation & promotes disaggregation; it's neuroprotective & BBB permeable.

R-137696 is an orally active 5-HT1A receptor agonist that facilitates the relaxation of the proximal stomach. It is utilized in research related to functional dyspepsia.

Cyproflanilide is a GABAR antagonist that exhibits high activity against a variety of pests, including those from the Lepidoptera, Coleoptera, and Thysanoptera orders.

MAO-B inhibitor 2: potent, reversible, oral, selective (IC50=1.33 nM), BBB-penetrant, with anti-oxidant and anti-inflammatory effects for Parkinson's study.

MAO-A inhibitor3 (Compound 360) is an MAO-A inhibitor with an IC50 greater than 100 μM. It is utilized in the investigation of neurological disorders.

Flucopride (Compound 4a) acts as an acetylcholinesterase inhibitor (AChE) with an IC50 value of 24 nM and serves as a partial agonist for the human 5-HT4 receptor (5-HT4R) with a Ki of 9.6 nM for (h)5-HT4R. It promotes non-amyloidogenic processing of APP in COS-7 cells transiently expressing (h)5-HT4R with an EC50 of 23.0 nM. Flucopride is also likely to exhibit significant gastrointestinal tract (GIT) penetration and blood-brain barrier (BBB) permeability, as determined in PAMPA experiments.

hAChE-IN-10 (Compound ET11) is an inhibitor of human acetylcholinesterase (AChE) with an IC50 of 6.34 nM. This compound is capable of scavenging free radicals and exhibits antioxidant activity. Additionally, hAChE-IN-10 demonstrates metal-chelating properties, inhibiting Cu2+-induced Aβ1-42 aggregation, reducing amyloid plaque formation, and offering neuroprotective effects. It also ameliorates cognitive impairment in mice induced by Scopolamine.

GABA-IN-4 (Compound 17) is a derivative of N-(indol-3-ylglyoxylyl)benzylamine. It exhibits high affinity for the benzodiazepine receptor (BzR), the binding site within the GABAA receptor complex, with a Ki value of 67 nM. Benzodiazepines are widely used as anxiolytic, sedative-hypnotic, and anticonvulsant agents.

Tebideutorexant, an orexin-1 receptor antagonist, shows anti-panic effects in rodents and humans, providing a tool for stress response and psychiatric research.

D3/5-HT receptor modulator-1 (compound 5i) is a selective antagonist of the dopamine D3 and 5-HT2A receptors, and a partial agonist at the 5-HT1A receptor. It exhibits Ki values of 4.5 nM, 11.9 nM, and 15.3 nM for the dopamine D3, 5-HT2A, and 5-HT1A receptors respectively. The compound shows lower affinity for the dopamine D2 receptor, 5-HT2C receptor, and hERG channel. D3/5-HT receptor modulator-1 possesses atypical antipsychotic properties.

Compound 2o, also known as CB2R/5-HT1AR agonist 1, serves as a partial orally active agonist for the CB2 receptor (EC50 = 479.6 nM) and a full agonist for the 5-HT1A receptor (EC50 = 2.7 μM). This compound demonstrates both anti-anxiety and anti-depressive effects and has favorable pharmacokinetic properties [1].

25B-NBOH hydrochloride is a phenethylamine that exhibits high affinity for serotonin (5-HT) receptors 5-HT2A and 5-HT2C, with pKi values of 8.3 and 9.4, respectively.

Amyloid-β-IN-2 (Compound EX.112) is a selective inhibitor of γ-secretase. In H4 cells, it demonstrates inhibitory activity on Aβ42 secretion, with an EC50 value of 226 nM. Amyloid-β-IN-2 holds potential for research in Alzheimer's disease (AD) and diseases associated with Aβ deposition.

LY3020371 HCl: potent mGlu2/3 antagonist, antidepressant-like; Ki: 5.3/2.5 nM, IC50: 16.2 nM for cAMP inhibition.

Elzasonan hydrochloride is a serotonin 1B and serotonin 1D receptor antagonist. It is utilized in the study of depression.

YNT-3708 is an orexin receptor (OXR) agonist, exhibiting EC50 values of 14.6 nM for OX1R and 277 nM for OX2R.

Aβ42 agonist-1 is a small molecule compound with anti-cancer activity and NF-κB inhibitory properties, inducing Aβ42 aggregation.

AChE-IN-11 aids Alzheimer's research, has neuroprotection/antioxidant properties (ORAC=2.5), and acts on AChE, MAO-B, BACE1 with IC50 values of 7.9-9.9 μM.

5-HT6R/MAO-B modulator 1 blocks 5-HT6R and permanently inhibits MAO-B, protects glial cells, and reverses memory loss.

Compound B15, a potent α7 nAChR antagonist, IC50 = 3.3 μM, promising for research on schizophrenia, Alzheimer's, and inflammation.

hMAO-B-IN-10 (compound 7) is an inhibitor of MAO-A/B with IC50 values of 424.1 nM and 177.9 nM, respectively. It has demonstrated neuroprotective effects in the MPTP-induced mouse model of Parkinson's Disease (PD).

γ-Secretase modulator 11 hydrochloride is a potent, orally active γ-secretase modulator (IC50: 0.029 μM).

Potent 5-HT6/5-HT2A receptors dual antagonist with K i of 11 nM & 39 nM.

(S)-Praziquantel is the inactive isomer of R-praziquantel.

Aβ aggregation-IN-1 (Compound 1b) is an inhibitor of amyloid-beta precursor protein. It suppresses the aggregation and disaggregation of amyloid-beta fibrils with IC50 values of 3.92 and 7.19 M, respectively. Additionally, Aβ aggregation-IN-1 reduces malondialdehyde formation in neuronal cells, increases intracellular levels of reduced glutathione (GSH), and inhibits caspase 3.

LY367385 hydrochloride: selective mGluR1a antagonist, IC50 = 8.8 μM, neuroprotective, anticonvulsant, antiepileptic.

Beloxepin is an oral dual selective inhibitor of serotonin and norepinephrine uptake.

AChE/BuChE-IN-3 inhibits AChE (IC50: 0.65 μM), BuChE (IC50: 5.77 μM), crosses BBB, and hinders Aβ1-42 aggregation for Alzheimer's research.

AChE-IN-24: Strong AChE blocker, crosses blood-brain barrier, IC50=0.053 μM, useful for AD research.

CVN636, a potent and selective allosteric agonist for the mGluR7 receptor, exhibits oral activity and CNS permeability [1], with an EC50 of 7 nM for human

Amyloid-β-IN-3 (EX.113) is a selective inhibitor of γ-secretase. It demonstrates inhibitory activity on Aβ42 secretion in H4 cells, with an EC50 value of 148 nM. By modulating the catalytic activity of γ-secretase, Amyloid-β-IN-3 decreases Aβ42 production, thereby alleviating neurotoxicity caused by Aβ deposition. It holds potential for Alzheimer's disease (AD) research.