GABAA receptor agent 1 is a high affinity ligand for GABAA receptor, with potent anticonvulsant activity[1].
Org37684 is a highly potent 5-HT2C receptor agonist (pEC50=8.17). Org37684 exhibits a rank order of potency of 5-HT2C>5-HT2B>5-HT2A. Its selectivity for the 5-HT2C receptor is approximately 2.5 times over the 5-HT2B (pEC50=7.96) and ten times for the 5-HT2A (pEC50=7.11) receptor[1].
β-Secretase Inhibitor I is an extremely potent β-secretase inhibitor with reduced cardiovascular and liver toxicity.
GR 128107 is an antagonist of melatonin receptor.
(-)-Borneol has a highly efficacious positive modulating action at GABA receptor with an EC50 of 237 μM.
Propantheline bromide is an antimuscarinic agent, used for the treatment of hyperhidrosis, cramps or spasms of the stomach, intestines or bladder, and enuresis.
Zatosetron maleate is a potent and selective 5HT3 receptor antagonist.
Propanidid (Sombrevin; Fabantol) is a γ-aminobutyric acid type A (GABAA) receptor agonist and a short-acting non-barbiturate general anesthetic agent. Propanidid can decrease the arterial pressure[1][2].
QNZ46 is a NR2C/NR2D-selective NMDA receptor non-competitive antagonist (IC50 values are 3, 6, 229, and >300, >300 μM for NR2D, NR2C, NR2A, NR2B, and GluR1, respectively). IC50 value: 3 μM (for NR2D), 6 μM (for NR2C), 229 μM (for NR2D NR2A)Target: NR2D, NR2C, NR2Ain vitro: QNZ46 is a noncompetitive inhibitor of GluN2C/D containing NMDA receptors. KD and IC50 values for binding and inhibition of GluN1/Glun2D receptors by QNZ46 are 4.9 and 3.9 μM, respectively. QNZ46 does not compete for binding of glutamate or glycine, but QNZ46 receptor binding requires the binding of glutamate to the GluN2 subunit.
Trimipramine is a 5-HT receptor antagonist, with pKi binding values of 6.39, 8.10, 4.66 for 5-HT1C, 5-HT2 and 5-HT1A, respectively. Trimipramine is also a potent and selective inhibitor targeting human noradrenaline (hNAT), serotonin (hSERT) and organic cation transporters (hOCT1, hOCT2) with IC50 values of 4.99 μM, 2.11 μM, 3.72 μM, 8.00 μM, respectively. Trimipramine has vascular activity and anxiolytic efficacy[1][2][3].
Elenbecestat (E2609) is a novel potent BACE-1 inhibitor for the treatment of Alzheimer's disease (AD)[1].
Fosaprepitant (L-758298) is a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting.IC50 Value:Target: NK1 receptorin vitro: Fosaprepitant (also known as MK-0517 and L-758,298) is a water-soluble phosphoryl prodrug for aprepitant, which, when administered intravenously, is converted to aprepitant within 30 min of intravenous administration via the action of ubiquitous phosphatases. Owing to the rapid conversion offosaprepitant to the active form (aprepitant), fosaprepitant 115 mg provided the same aprepitant exposure in terms of AUC as aprepitant 12 mg orally, and fosaprepitant is expected to provide a correspondingly similar antiemetic effect as aprepitant [1]. in vivo: Fosaprepitant is well tolerated with mild to moderate venous irritation being the only additional toxicity to those seen with oral aprepitant, and that is a function of dose, concentration, and infusion rate [2]. Patients receiving cisplatin ≥ 70 mg/m(2) for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1) [3]. Single-dose fosaprepitant used in combination with granisetron and dexamethasone was well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic cancer chemotherapy, including high-dose cisplatin [4].
Mosapramine (Clospipramine) is an orally active and potent dopamine receptor antagonist with high affinity to dopamine receptor subtypes 2, 3 and 4, and with moderate affinity for the 5-HT2 receptor. Mosapramine shows antipsychotic activity and can be used in schizophrenia research[1][2].
PE154 (Compound 13) is a potent fluorescent inhibitor of human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (IC50s=280 pM and 16 nM, respectively)[1]. PE154 can label β-amyloid plaques in histochemical analysis[2].
Landipirdine is a selective antagonist of 5-HT6R. Landipirdine has great effect on the hERG pharmacophore[1].
Brompheniramine ((±)-Brompheniramine) is a potent and orally active antihistamine of the alkylamine class. Brompheniramine is a selective histamine H1 receptor antagonist with a Kd of 6.06 nM. Brompheniramine can block the hERG channels, calcium channels, and sodium channels with IC50s of 0.90 μM, 16.12 μM and 21.26 μM, respectively. Brompheniramine has anticholinergic, antidepressant and anesthetic properties and can be used for allergic rhinitis research[1][2][3][4].
Sulindac sulfide is a noncompetitive γ-secretase inhibitor, with an IC50 of 20.2 μM for γ42-secretase activity.
BChE/HDAC6-IN-1 is a potent and selective dual BChE/HDAC6 inhibitor with IC50 values of 4 and 8.9 nM, respectively. BChE/HDAC6-IN-1 ameliorates the cognitive impairment in an Aβ1–42-induced mouse model and has the potental for AD research[1].
KN-92 is an inactive derivative of KN-93. KN-93 is a selective inhibitor of Ca2+/calmodulin-dependent kinase II (CaMKII), competitively blocking CaM binding to the kinase (Ki = 370 nM). IC50 value:Target: KN-92 is intended to be used as a control compound in studies designed to elucidate the antagonist activities of KN-93. KN-93 inhibits histamine-induced aminopyrine uptake in parietal cells (IC50 = 300 nM). KN-93 has been used to implicate roles for CaMKII in Ca2+-induced Ca2+ release in cardiac myocytes, constitutive phosphorylation of 5-lipoxygenase in 3T3 cells, and Ca2+-dependent activation of HIF-1α in colon cancer cell.
Pirenzepine (LS 519 free base) is a selective M1 mAChR (muscarinic acetylcholine receptor) antagonist. Pirenzepine reduces gastric acid secretion and reduces muscle spasm, can be used in peptic ulcers research. Pirenzepine shows anti-proliferative activity to cancer cells[1][2].
Protopine hydrochloride, an isoquinoline alkaloid, is a specific reversible and competitive inhibitor of acetylcholinesterase. Protopine hydrochloride exhibits anti-inflammation, anti-microbial, anti-angiogenic and anti-tumour activity[1][2].
PF-3845 is a selective fatty acid amide hydrolase (FAAH) inhibitor (Ki = 0.23 μM); showing negligible activity against FAAH2.IC50 value: 0.23 uMTarget: FAAHPF-3845 selectively inhibits FAAH by carbamylating FAAH's serine nucleophile [1]. PF-3845 treated mice (10 mg/kg, i.p.) shows rapid and complete inactivation of FAAH in the brain, as judged by competitive activity-based protein profiling (ABPP) with the serine hydrolase-directed probe fluorophosphonate (FP)-rhodamine. PF-3845 shows a long duration of action up to 24 hour. PF-3845-treated mice also shows dramatic (>10-fold) elevation in brain levels of AEA and other NAEs (N-pamitoyl ethanolamine [PEA] and N-oleoyl ethanolamine [OEA]). FAAH is AEA-degrading enzyme fatty acid amide hydrolase. PF-3845 (1–30 mg/kg, oral administration [p.o.]) causes a dose dependent inhibition of mechanical allodynia with a minimum effective dose (MED) of 3 mg/kg (rats are analyzed at 4 hour post dosing with PF-3845). At higher doses (10 and 30 mg/kg), PF-3845 inhibits pain responses to an equivalent, if not greater, degree than the nonsteroidal anti-inflammatory drug naproxen (10mg/kg, p.o.) [1]. PF-3845 (10 mg/kg, i.p.) significantly reverses LPS-induced tactile allodynia, but doesn't modify paw withdrawal thresholds in the saline-injected paw [2].
UBP 302, the S enantiomer, is a potent and selective GluK1 (GluR5)-subunit containing kainate receptor antagonist (apparent Kd=402 nM), and displays very little affinity on GluK2 (GluR6) kainate receptors. Anxiolytic effects[1][2][3].
Prucalopride hydrochloride is an orally active, selective and specific 5-HT4 receptor agonist (high affinity), with pKis of 8.6 and 8.1 for human 5-HT4a/4b receptors, respectively. Prucalopride hydrochloride improves intestinal motility by promoting regeneration of the intestinal nervous system in rats. Prucalopride hydrochloride also shows anticancer activity by blocking of the PI3K/AKT/mTor signaling pathway. Prucalopride hydrochloride can be used in studies of chronic constipation, pseudo-intestinal obstruction and cancer[1][2][3].
(±)-J-113397 is a potent and selective non-peptidyl ORL1 receptor antagonist with a Ki of 1.8 nM for cloned human ORL1. J-113397 inhibited nociceptin/orphanin FQ-stimulated GTPγS binding to CHO cells expressing ORL1 with an IC50 value of 5.3 nM. J-113397 can be used for researching the physiological roles of nociceptin/orphanin FQ[1].
Piboserod (SB 207266) Hcl is a selective 5-HT(4) receptor antagonist.IC50 value:Target: 5-HT4 antagonistin vitro: Piboserod did not modify the basal contractions but concentration-dependently antagonized the ability of 5-HT to enhance bladder strip contractions to EFS. In presence of 1 and 100 nM of piboserod, the maximal 5-HT-induced potentiations were reduced to 45.0+/-7.9 and 38.7+/-8.7%, respectively [1].in vivo: Piboserod significantly increased LVEF by 1.7% vs. placebo (CI 0.3, 3.2, P = 0.020), primarily through reduced end-systolic volume from 165 to 158 mL (P = 0.060). There was a trend for greater increase in LVEF (2.7%, CI -1.1, 6.6, P = 0.15) in a small subset of patients not on chronic beta-blocker therapy. There was no significant effect on neurohormones, quality of life, or exercise tolerance. Patients on piboserod reported more adverse events, but numbers were too small to identify specific safety issues [2]. Pretreatment with potent 5-HT4 ligands dose-dependently reduced striatal SB207145 concentration and the effective dose to achieve 50% receptor occupancy (ED50 ) values were 4.8, 2.0, 7.4, 9.9, 3.8 and 0.02 mg/kg for GR113808, piboserod, prucalopride, RS67333, TD8954 and PF04995274, respectively [3].
[Sar9,Met(O2)11]-Substance P is a tachykinin NK1 receptor selective agonist.
DU125530 is a potent and selective5-HT1A receptor antagonist with Ki values of 0.7, 890, 1200, 240, 750, 1100 nM for 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2C, 5-HT3, respectively. DU125530 shows antidepressant effects[1][2].
DAMGO TFA is a μ-opioid receptor (μ-OPR ) selective agonist with a Kd of 3.46 nM for native μ-OPR[1].
L-Phenylalanine-13C9,d8,15N ((S)-2-Amino-3-phenylpropionic acid-13C9,d8,15N) is the deuterium, 13C-, and 15-labeled L-Phenylalanine. L-Phenylalanine ((S)-2-Amino-3-phenylpropionic acid) is an essential amino acid isolated from Escherichia coli. L-Phenylalanine is a α2δ subunit of voltage-dependent Ca+ channels antagonist with a Ki of 980 nM. L-phenylalanine is a competitive antagonist for the glycine- and glutamate-binding sites of N-methyl-D-aspartate receptors (NMDARs) (KB of 573 μM ) and non-NMDARs, respectively. L-Phenylalanine is widely used in the production of food flavors and pharmaceuticals[1][2][3][4].