q-FTAA binds to Aβ1-42 fibrils with EC50 values of 330-630, 300-500 nM for Aβ1-42 fibrils, alzheimer's disease PIB binding complex (ADPBC) , respectively. q-FTAA has the potential for the research of Alzheimer's disease (AD)[1].
H-9 Dihydrochloride is a PKA (protein kinase) inhibitor. H-9 Dihydrochloride (10 μM) significantly reduces the excitatory response to 5-HT. H-9 Dihydrochloride also has a direct effect on pharyngeal activity. H-9 Dihydrochloride inhibits signal-transduction and cell growth in EGF (epidermal growth factor)-dependent epithelial cell lines[1][2][3].
L-663581 (FG-8205) is an agonist of benzodiazepine receptor, acting as a partial agonist at GABA A receptor[1].
CP 316311 is a potent and selective CRF1 receptor antagonist with an IC50 value of 6.8 nM.
BPN-15606 is a highly potent, orally active γ-secretase modulator (GSM)， attenuates the production of Aβ42 and Aβ40 by SHSY5Y neuroblastoma cells with IC50 values of 7 nM and 17nM, respectively. BPN-15606 significantly lowers Aβ42 and Aβ40 levels in the central nervous system of rats and mice. BPN-15606 has acceptable PK/PD properties, including bioavailability, half-life, and clearance[1].
Muscarine ((+)-Muscarine) iodide is a toxin that can stimulate the parasympathetic nervous system. Muscarine iodide is a prototype muscarinic acetylcholine receptor agonist[1][2].
LRRK2-IN-1 is a potent and selective LRRK2 inhibitor with IC50 of 6 nM and 13 nM for LRRK2 (G2019S) and LRRK2 (WT), respectively.
Kelatorphan is a full inhibitor of enkephalin degrading enzymes.
Oligomycin B is an antibiotic isolated from marine Streptomyces, used as an eukaryotic ATP synthase inhibitor, induces apoptosis[1][2].
TQS is a α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator. TQS can be used for the research of neuroinflammatory pain[1].
[Glp6] Substance P (6-11) is an analogue of substance P (6-11). Substance P (6-11) stimulates [3H]-inositol monophosphate ([3H]-IP1) formation in rat urinary bladder by acting on the 'septide-sensitive' tachykinin receptors[1][2].
ML-SI3 is a TRPML Channel Inhibitor. ML-SI3 blocks TRPML1 and TRPML2 with IC50s of 4.7 µM and 1.7 µM respectively. ML-SI3 prevents lysosomal calcium efflux and blocks downstream TRPML1-mediated induction of autophagy[1][5].
Indirubin-3′-oxime (IDR3O), a synthetic derivative of indirubin, is a potent inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3β (GSK3β). Indirubin-3′-oxime directly inhibits the activity of all three isoforms of JNK (JNK1, JNK2, and JNK3), with IC50s of 0.8 μM, 1.4 μM, and 1.0 μM, respectively. Indirubin-3′-oxime can enhance height growth via activation of Wnt/β-catenin signaling in chondrocytes[1][2][3].
Lofepramine (Lopramine) hydrochloride is a potent tricyclic antidepressant and is extensively metabolised to Desipramine. The antidepressant activity of Lofepramine hydrochloride stems from the facilitation of noradrenergic neurotransmission by uptake inhibition. Lofepramine hydrochloride may also potentiate serotoninergic neurotransmission by inhibition of the neuronal uptake of serotonin and the enzyme tryptophan pyrrolase. Lofepramine hydrochloride has significant anxiolytic efficacy in addition to its antidepressant properties[1].
Tazomeline is a selective M1 muscarinic receptor agonist. Tazomeline inhibits twitch height in rabbit vas deferens(IC50= 0.001 nM). Tazomeline can be used for research of neuropsychiatric disorders[1].
TAT-M2NX (tatM2NX) is a TRPM2 inhibitor with specific neuroprotective activity in male mice. TAT-M2NX can be used to study ischemic neuronal damage[1].
Neuroinflammatory-IN-3, a tubulin inhibitor, is an anti-neuroinflammatory agent. Neuroinflammatory-IN-3 is a potent antitumor agent that functions by the inhibition of tubulin polymerization[1][2].
Semorinemab (RG 6100) is an anti-Tau humanized IgG4 monoclonal antibody, targets the N-terminal portion of the Tau protein. Semorinemab binds with human Tau with a Kd value of 3.8 nM. Semorinemab can be used for the research of Alzheimer's Disease[1].
Ligustroside (Ligstroside), a secoiridoid derivative, has outstanding performance on mitochondrial bioenergetics in models of early Alzheimer's disease (AD) and brain ageing by mechanisms that may not interfere with Aβ production. Ligustroside significantly inhibits nitric oxide production in lipopolysaccharide-activated RAW264.7 macrophages[1][2].
Epi-galanthamine-O-methyl-d3 is the deuterium labeled Epi-galantamine. Epi-galantamine is a diastereomer of Galantamine. Epi-galantamine is an alkaloid isolated from the bulbs and flowers of Caucasian snowdrop (Galanthus woronowii). Epi-galantamine inhibits AChE with an EC50 of 45.7 μM[1][2][3].
Ecopipam (SCH 39166) hydrochloride is a potent, selective and orally active antagonist of dopamine D1/D5 receptor, with Kis of 1.2 nM and 2.0 nM, respectively. Ecopipam hydrochloride shows more than 40-flod selectivity over D2, D4, 5-HT, and α2a receptor (Ki=0.98, 5.52, 0.08, and 0.73 μM, respectively). Ecopipam hydrochloride can be used for the research of schizophrenia, cocaine addition, and obesity[1][3].
[D-Trp11]-Neurotensin, an analogue of Neurotensin (NT), is a selective antagonist of NT in perfused rat hearts but behaves as a full agonist in guinea pig atria and rat stomach strips. [D-Trp11]-Neurotensin can inhibit NT-induced hypotension[1][2].
Melatonin receptor agonist 1 (compound 20c) is a potent melatonin receptor (MT) agonist, with Ki values of 108 nM (MT2) and 1140 nM (MT1)[1].
PH-002 is an inhibitor of apolipoprotein (apo) E4 intramolecular domain interaction in neuronal cells that could rescue impairments of mitochondrial motility and neurite outgrowth.
hnNOS-IN-2 (compound 17) is a human neuronal nitric oxide synthase (hnNOS) inhibitor with good metabolic stability. hnNOS-IN-2 can be used for research in neurodegenerative diseases[1].
Aβ-IN-5 (Compound e12) is an orally active Aβ aggregation inhibitor. Aβ-IN-5 also inhibits AChE and BuChE with IC50 values of 21.29 μM and 1.32 μM, respectively. Aβ-IN-5 shows excellent neuroprotective effects and low neurotoxicity[1].
Butylphthalide(3-n-Butylphthalide) is an anti-cerebral-ischemia drug; first isolated from the seeds of celery, showed efficacy in animal models of stroke.IC50 value:Target:3-n-butylphthalide alleviates oxidative stress caused by chronic cerebral ischemia, improves cholinergic function, and inhibits amyloid beta accumulation, thereby improving cerebral neuronal injury and cognitive deficits [2]. Intragastric NBP administration to 4-month-old SAMP8 mice for 2 months significantly improved spatial learning and memory ability. Moreover, the loss of choline acetyltransferase (ChAT)-positive neurons in the medial septal nucleus and the vertical limb of the diagonal band in SAMP8 mice was slowed down, as was the decline in the protein and mRNA expression of ChAT in the hippocampus, cerebral cortex, and forebrain [4].
ML402 is a selective TREK-1 activator.
SB271046 Hcl is a potent, selective and orally active 5-HT6 receptor antagonist with pKi of 8.9.IC50 Value: 8.9(pKi)Target: 5-HT6 Receptorin vitro: SB 271046 hydrochloride is a sulfonamidal benzothiophene derivative that has been shown to act as a selective 5-HT6 antagonist with pKi values of 9.02-8.92, 6.55, 6.35, 6.27, 6.05, 5.95, 5.76, 5.73, 5.62, 5.55, 5.41, 5.39, 5.27 and < 4.99 for 5-HT6, 5-HT1D, 5-HT1A, D3, 5-HT1B, 5-HT1F, α1B, 5-HT2C, 5-HT2A, D2, 5-HT2B, 5-HT7, 5-HT4 and 5-HT1E respectively, and is > 200-fold selective over 55 other receptors, enzymes and ion channels.in vivo: SB-271046 is moderately brain penetrant (10%), subject to low blood clearance (7.7 mL/min/kg) with a good half-life in rats (4.8 hours), and has excellent oral bioavailability (>80%). SB-271046 produces 3-fold and 2-fold increases in extracellular glutamate levels in both frontal cortex and dorsal hippocampus of rats, respectively, which may be used for the treatment of cognitive and memory dysfunction. SB-271046 (20 mg/kg, orally gavage) 30 min prior to training Wistar rats, is found to reverse significantly the amnesia produced by administering scopolamine (0.8 mg/kg, i.p.) in the 6 hours post-training period. SB-271046 progressively and significantly decreases platform swim angle and escape latencies over the five sequential trials on four consecutive daily sessions compared to vehicle-treated controls in aged rats. SB-271046 also improves task recall as measured by significant increases in the searching of the target quadrant on post-training days 1 and 3. SB-271046 (10 mg/kg, s.c.) produces a significant, tetrodotoxin-dependent, increase in extracellular levels of both glutamate and aspartate within the frontal cortex of rats, reaching maximum values of 375.4% and 215.3% of preinjection values, respectively.
Diarylpropionitrile(DPN) is a non-steroidal estrogen receptor β(ER β) selective ligand.IC50 value:Target: ER β ligandin vitro: Pre-treatment with 1-100 nM DPN significantly decreased neuronal cell death by increasing cell viability through a significant attenuation in the reactive oxygen species level, downregulation of pro-apoptotic activated caspase-3 and Bax, and upregulation of anti-apoptotic Bcl-2, thereby mitigating apoptotic morphological alterations. DPN pre-treatment decreased the expression levels of pro-inflammatory cytokines IL-1β and IL-6 through attenuation of Aβ1-42-induced phosphorylation of mitogen-activated protein kinases JNK and p38. In addition, DPN enhanced ERK1/2 and Akt phosphorylation depressed by Aβ1-42 [1]. ERβ was expressed in RAW264.7 cells, and DPN statistically significantly decreased LPS-induced RANTES production in RAW264.7 cells. Small interfering RNA targeting the ERβ gene inhibited the effect of DPN on RANTES production. In addition, DPN inhibited nuclear translocation and phosphorylation of p65 by inhibiting IκB degradation and thus prohibited the activation of nuclear factor κB (NF-κB) [3].in vivo: DPN treatment during EAE did not attenuate demyelination, only partially improved axon conduction, and did not activate the phosphatidylinositol 3-kinase/serine-threonine-specific protein kinase/mammalian target of rapamycin signaling pathway in ERβ CKO mice [2].