Grossamide is a natural product that can be isolated from fructus cannabis, the dried fruit of Cannabis sativa L.. Grossamide has anti-neuroinflammatory effects[1].
Macelignan(Anwuligan) is a natural compound isolated from Myristica fragrans Houtt; possesses therapeutic potentials against neurodegenerative diseases with oxidative stress and neuroinflammation.IC50 value:Target: in vitro: Macelignan significantly attenuated the ROS production and neurotoxicity induced by glutamate in HT22 cell [1]. At 24 h of biofilm growth, S. mutans, A. viscosus and S. sanguis biofilms were reduced by up to 30%, 30% and 38%, respectively, after treatment with 10 microg/mL macelignan for 5 min [2]. Cisplatin-induced phosphorylation of c-Jun N-terminal kinase1/2 (JNK1/2) and extracellular signal-regulated kinase1/2 (ERK1/2) was abrogated by pretreatment with macelignan, however, that of p38 was not significantly affected [3].in vivo: Macelignan attenuated the expression of phosphorylated c-Jun in cisplatin-treated mice [3]. Daily administration of macelignan reduced the spatial memory impairments induced by the chronic LPS infusions [4].
Galanin-B2 (NAX-5055) has activity in the epilepsy model. Galanin-B2 can penetrate the blood-brain-barrier[1].
Deltorphin I is a δ-opioid receptor agonist with high affinity and selectivity.
PDE10-IN-2 is a PDE10 inhibitor with an IC50≦0.01 μM[1].
4-Chloro-L-phenylalanine (L-PCPA) is a 5-HT biosynthesis inhibitor. 4-Chloro-L-phenylalanine is also a nonspecific antagonist of both isoforms of tryptophan hydroxylase (TPH1 and TPH2)[1].
(RS)-PPG is a potent and selective agonist for group III mGluRs. The EC50s of 5.2 μM, 4.7 μM, 185 μM, and 0.2 μM for hmGluR4a, hmGluR6, hmGluR7b, and hmGluR8a, respectively. Anticonvulsive and neuroprotective activity[1].
Netupitant (CID-6451149) is a highly potent and selective, orally active neurokinin-1 receptor antagonist with Ki of 0.95 nM.IC50 value: 0.95 nM (Ki) [1]Target: NK1 receptorin vitro: Netupitant also dose-dependently inhibited the SP response as expected from an NK1 receptor antagonist. Importantly, when both palonosetron and netupitant were present, they exhibited an enhanced inhibition of the SP response compared to either of the two antagonists alone [2].in vivo: In mice the intrathecal injection of SP elicited the typical scratching, biting and licking response that was dose-dependently inhibited by Netupitant given intraperitoneally in the 1-10mg/kg dose range. In gerbils, foot tapping behavior evoked by the intracerebroventricular injection of a NK(1) agonist was dose-dependently counteracted by Netupitant given intraperitoneally (ID(50) 1.5mg/kg) or orally (ID(50) 0.5mg/kg) [3].
Risdiplam is an orally administered, centrally and peripherally distributed SMN2 pre-mRNA splicing modifier that increases survival motor neuron (SMN) protein levels.
Levetimide is a potent and stereoselective inhibitor of [3H](+)pentazocine binding, with a Ki of 2.2 nM[1].
Picroside IV is an iridoid glycoside found in the underground parts of Picrorhiza scrophulariiflora. Picroside IV is a derivative of Catalpol (HY-N0820)[1]. Catalpol has neuroprotective, hypoglycemic, anti-inflammatory, anti-cancer, anti-spasmodic, anti-oxidant effects and anti-HBV effects[2].
RXFP3/4 agonist 2 is a potent, nonpeptide dual RXFP3/4 agonist (EC50=3.1 and 2.7 nM). RXFP3/4 agonist 2 also potently promotes interactions between RXFP3 and β-arrestin-2 with EC50 values in the range of 10-22 nM[1].
BChE-IN-17 (compound 6n) is a potent and selective BChE inhibitor with IC50s of 10.5 nM and 32.5 nM for eqBChE and hBChE, respectively. BChE-IN-17 shows over 1000-fold selectivity to BChE against AChE. BChE-IN-17 shows low neurotoxicity and moderate neuroprotective effects[1].
NKP608 is a non-peptidic derivative of 4-aminopiperidine which acts as a selective, specific and potent antagonist at the neurokinin-1 (NK-1) receptor both in vitro(IC50=2.6 nM) and in vivo. IC50 value: 2.6 nMTarget: NK-1 receptorIn vitro, the binding of NKP608 to bovine retina was characterized by an IC50 of 2.6+/-0.4 nM, whereas the compound's affinity to other receptor binding sites, including NK-2 and NK-3, was much lower. Species differences in IC(50) values with NKP608 were less pronounced than with previously described NK-1 receptor antagonists, being 13+/-2 and 27+/-2 nM in gerbil midbrain and rat striatum, respectively. In vivo, using the hind foot thumping model in gerbils, NKP608 exhibited a potent NK-1 antagonistic activity following oral administration (ID(50)=0.23 mg/kg; 2 h pretreatment), supporting a central activity of NKP608. NKP608 may prove a useful anxiolytic compound.
Nelonicline (ABT-126) is a selective neuronal nicotinic receptor agonist.
Trimipramine N-oxide is an active metabolite of the tricyclic antidepressant trimipramine. Trimipramine N-oxide inhibits the human monoamine transporters for noradrenaline (hNAT), serotonin (hSERT), dopamine (hDAT) and the human organic cation transporters (hOCT1 and hOCT2) with IC50s of 11.7, 3.59, 9.4, 9.35 and 27.4 nM, respectively. Trimipramine N-oxide can be used for the research of depression and anxiety[1].
HDAC-IN-58 is a HDAC inhibitor. HDAC-IN-58 has HDAC6-specific inhibition activity with an IC50 value of 2.06 nM. HDAC-IN-58 can be used for the research of chronic diseases, including neurodegenerative and psychiatric conditions[1].
Theophyllol (theophylline sodium acetate) can alter calcium levels in subcellular fractions of rat brain cortex[1].
Kaurenoic acid is a diterpene from Sphagneticola trilobata, inhibits Inflammatory Pain by the inhibition of cytokine production and activation of the NO–cyclic GMP–PKG–ATP-sensitive potassium channel signaling pathway[1].
TVP1022 is the S-isomer of rasagiline, which is an anti-Parkinson drug, appears to have the same neuroprotective activity as the R-isomer, but is 1000-fold less active as an MAO-B inhibitor.
DQP-997-74 (compound 2i) is a selective inhibitor of N-methyl-d-aspartate receptor (NMDAR), specifically targeting GluN2C/D (IC50: 0.069 μM and 0.035 μM), with Blood-brain permeability. Where DQP refers to dihydroquinoline-pyrazoline. DQP-997-74 acts synergistically with the agonist glutamate to exhibit time-dependent enhanced potency in inhibiting hypersynchronous activity driven by high-frequency excitatory synaptic transmission. DQP-997-74 reduces the number of epileptogenesis in a murine model of tuberous sclerosis complex (TSC)-induced epilepsy. DQP-997-74 can be used for research on NMDAR-related neurological diseases[1].
TSPO ligand-1 is the ligand of AUTAC4 (HY-134640) that can be used in the synthesis of PROTACs. TSPO ligand-1 is a mitochondrial outer membrane transmembrane structural domain protein can bind to AUTAC4 and regulate mitochondrial autophagy to promote targeted mitochondrial renewal. TSPO ligand-1 is also involved in the transport of cholesterol from the outer to inner mitochondrial membrane and serves as a sensitive biomarker of brain injury and neurodegeneration[1][2].
MIF-1 (Melanostatin), an endogenous brain peptide, is a potent dopamine receptor allosteric modulator. MIF-1 inhibits melanin formation. MIF-1 blocks the effects of opioid receptor activation to modulate the analgesic effects of morphine and stress-induced analgesia (SIA). MIF-1 accesses from the blood to the CNS by directly crossing the blood-brain barrier (BBB)[1][2][3].
(S)-Minzasolmin is an isomer of minzasolmin (HY-145580), an inhibitor of α-synuclein oligomerization[1].
[D-Arg2]Dermorphin-(1-4) amide is a N-terminal shorter peptide amide of [D-Arg2]dermorphin with the hypothermic effect. [D-Arg2]Dermorphin-(1-4) amide shows analgesic activity and degradation in soluble mouse liver and brain extracts[1].
FG 7142 (ZK 39106; LSU-65), a non-selectively benzodiazepine inverse agonist, has high affinity for the α1 subunit-containing GABAA receptor (Ki=91 nM). FG 7142 (ZK 39106; LSU-65) also modulates GABA-induced chloride flux at GABAA receptors expressing the α1 subunit (EC50= 137 nM). FG 7142 (ZK 39106; LSU-65) can increase tyrosine hydroxylation and cause upregulation of β-adrenoceptors in mouse cerebral cortex[1].
SR-3737 is potent both JNK3 and p38 inhibitor.
Minzasolmin is an alpha-synuclein oligomerization inhibitor[1].
Sulpiride is a D2 receptor a antagonist, an atypical antipsychotic drug of the benzamide class, used mainly in the treatment of psychosis associated with schizophrenia and major depressive disorder, and sometimes used in low dosage to treat anxiety and mild depression.
JNJ-5207787 is a nonpeptidic, selective and penetrate the blood-brain barrier neuropeptide Y Y2 receptor (Y2) antagonist. JNJ-5207787 inhibits the binding of peptide YY (PYY) with pIC50s of 7.0 and 7.1 for human Y2 receptor and rat Y2 receptor, respectively. JNJ-5207787 is >100-fold selective versus human Y1, Y4, and Y5 receptors[1].