CFTR activator 1 is a potent and selective CFTR activator, with an EC50 of 23 nM. CFTR activator 1 can be used to ameliorate dry eye disease[1].
Prilocaine is a local anesthetic of the amino amide type.Target: OthersPrilocaine is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils L?fgren. In its injectable form (trade name Citanest), it is often used in dentistry. It is also often combined with lidocaine as a preparation for dermal anesthesia, for treatment of conditions like paresthesia. As it has low cardiac toxicity, it is commonly used for intravenous regional anaesthesia (IVRA). In some patients, a metabolite of prilocaine may cause the unusual side effect of methemoglobinemia, which may be treated with methylene blue. Maximum dosage for dental use: 8.0 mg/kg (2.7 mg/lb), with a maximum dose of 500 mg.Eutectic Mixture of Local Anesthetics (EMLA) containing 5% lidocaine and prilocaine in a cream was found to give effective topical analgesia in normal and diseased skin, making it useful for superficial surgery and various other clinical procedures. To be effective, an adequate amount must be applied under occlusion and at the right time before the intervention.
Varenicline Tartrate(CP 526555;Champix) is a nicotinic receptor partial agonist; it stimulates nicotine receptors more weakly than nicotine itself does.IC50 value:Target: α4β2 nAChRVarenicline(CP 526555; Champix; Chantix) is a prescription medication used to treat smoking addiction. As a partial agonist it both reduces cravings for and decreases the pleasurable effects of cigarettes and other tobacco products. Through these mechanisms Varenicline(CP 526555; Champix; Chantix) can assist some patients to quit smoking.
Nisoldipine(BAY-k 5552; Sular) is a calcium channel blocker belonging to the dihydropyridines class, specific for L-type Cav1.2 with IC50 of 10 nM. IC50 value: 10 nMTarget: L-type Cav1.2Nisoldipine is a potent blocker of L-type calcium channels. Nisoldipine binds directly to inactive calcium channels stabilizing their inactive conformation Similar to other DHP CCBs. Nisoldipine displays selectivity for arterial smooth muscle cells due to great number of inactive channels and the α1 subunit of the channel. Nisoldipine is about 30 times less selective for delayed-rectifier K+ channels than for L-type Ca2+ channels, which inhibits IKr (rapidly activating delayed-rectifier K+ current) with IC50 of 23 μM, and IKs (slowly activating delayed-rectifier K+ current)with IC50 of 40 μM in guinea-pig ventricular myocytes. Nisoldipine also displays antioxidant potency with IC50 of 28.2 μM both before and after the addition of active oxygen.
(20S)-Protopanaxadiol (20-Epiprotopanaxadiol) is an aglycon metabolic derivative of the protopanaxadiol-type ginseng saponin; apoptosis inducer.IC50 value:Target: apoptosis inducer(20S)-Protopanaxadiol was used to induce cytotoxicity for two human glioma cell lines, SF188 and U87MG. For the SF188 cells, (20S)-Protopanaxadiol activated caspases-3, -8, -7, and -9 within 3 h and induced rapid apoptosis, which could be partially inhibited by a general caspase blocker and completely abolished when the caspase blocker was used in combination with an antioxidant. (20S)-Protopanaxadiol also induced cell death in U87MG cells but did not activate any caspases in these cells [1]. aPPD was able to inhibit P-gp activity as potently as verapamil on MDR cells. The blockage of P-gp activity was highly reversible as wash-out of aPPD resulted in an immediate recovery of P-gp activity. Unlike verapamil, aPPD did not affect ATPase activity of P-gp suggesting a different mechanism of action [2].
Tetraethylammonium chloride is a non-selective potassium channel blocker. Tetraethylammonium chloride is a good substrate for organic cation transporter (OCTN1). Tetraethylammonium chloride antitumor properties[1][2].
(R)-(+)-Anatabine is an less active R-enantiomer of Anatabine. Anatabine is a potent α4β2 nAChR agonist[1]. Anatabine inhibits NF-κB activation lower amyloid-β (Aβ) production by preventing the β-cleavage of amyloid precursor protein (APP). Anatabine has anti-inflammatory effects and has the potential for neurodegenerative disorders treatment[2][3][4].
PF-4778574 is a positive allosteric modulation of AMPA receptor with EC50 of 45 to 919 nM in differenct cells.
Sunifiram (DM-235) is a piperazine derived ampakine-like drug which has nootropic effects in animal studies with significantly higher potency than piracetam.IC50 value: Target: in vitro: DM 232 and DM 235 are novel antiamnesic compounds structurally related to ampakines. The involvement of AMPA receptors in the mechanism of action of DM 232 and DM 235 was, therefore, investigated in vivo and in vitro. Both compounds (0.1 mg/kg i.p.) were able to reverse the amnesia induced by the AMPA receptor antagonist NBQX (30 mg/kg i.p.) in the mouse passive avoidance test. At the effective doses, the investigated compounds did not impair motor coordination, as revealed by the rota rod test, nor modify spontaneous motility and inspection activity, as revealed by the hole board test [1]. In mouse hippocampal slices, sunifiram at 10-100 nM significantly enhanced LTP in a bell-shaped dose-response relationship which peaked at 10 nM. The enhancement of LTP by sunifiram treatment was inhibited by 7-chloro-kynurenic acid (7-ClKN), an antagonist for glycine-binding site of NMDAR, but not by ifenprodil, an inhibitor for polyamine site of NMDAR [2].in vivo: OBX mice were administered once a day for 7-12 days with sunifiram (0.01-1.0 mg/kg p.o.) from 10 days after operation with or without gavestinel (10 mg/kg i.p.), which is glycine-binding site inhibitor of N-methyl-d-aspartate receptor (NMDAR) [3].
HTT-D3 is a potent and orally active huntingtin (HTT) splicing modulator. HTT-D3 acts by promoting the inclusion of a pseudoexon containing a premature termination codon (stop-codon psiExon), leading to HTT mRNA degradation and reduction of HTT levels. HTT-D3 reduces p-glycoprotein (P-gp) efflux, and can be uesd for Huntington's disease research[1].
Velagliflozin is an orally available sodium-glucose cotransporter 2 (SGLT2) inhibitor, with anti-diabetic activity.
Carbamazepine-d8 is the deuterium labeled Carbamazepine. Carbamazepine, a sodium channel blocker, is an anticonvulsant drug, with an IC50 of 131 μM[1][2].
Huwentoxin XVI, an analgesic, is a highly reversible and selective mammalian N-type calcium channel (IC50 of ~60 nM) antagonist from Chinese tarantula Ornithoctonus huwena. Huwentoxin XVI has no effect on voltagegated T-type calcium channels, potassium channels or sodium channels[1].
α-Conotoxin MrIC is an α7nAChR biased agonist. α-Conotoxin MrIC exclusively activates α7nAChR regulated by type II positive allosteric modulators, including PNU120596. α-Conotoxin MrIC can be used to study neurological diseases and also to probe the pharmacological properties of α7nAChR[1].
YS-201 is a dihydropyridine-type calcium channel antagonist previously in clinical trials for the treatment of angina pectoris and hypertension.
Pipequaline hydrochloride (PK-8165 hydrochloride) is a partial benzodiazepine receptor agonist with anxiolytic activity[1][2].
Zonampanel (YM 872) is a selective antagonist of the glutamate receptor subtype, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor.
Carbamoylcholine chloride is used to study responses mediated by nAChR and mAChR, including smooth muscle contraction, gut motility, and neuronal signaling.IC50 value: 10 to 10,000 nM (Ki)Target: nAChR, mAChRCarbamoylcholine is an analog of acetylcholine that activates acetylcholine receptors (AChR). Carbamoylcholine is an agonist of both nicotinic (nAChR) and muscarinic (mAChR) receptors, with reported Ki values ranging from 10 to 10,000 nM for different receptors and different preparations.
(Rac)-Monepantel sulfone-d5 is deuterium labeled Monepantel. Monepantel is organic anthelmintic, and acts as a positive allosteric modulator of a nematode-specific clade of nicotinic acetylcholine receptor (nAChR) subunits.
AMPA receptor modulator-5 (Example 217) is an AMPA receptor modulator. AMPA receptor modulator-5 can be used for research of neurological disease[1].
Lumacaftor (VX-809) is a CFTR modulator that corrects the folding and trafficking of CFTR protein.
TRPA1 Antagonist 1 is a methylene phosphate prodrug which converts to its active parent drug, a TRPA1 antagonist with an IC50 of 8 nM.
Huwentoxin I (HWTX-I) is a peptide toxin that inhibits voltage-gated sodium channels and N-type calcium channels. Huwentoxin I inhibits sodium channels in rat hippocampus and cockroach dorsal unpaired median (DUM) neurons with IC50 values of 66.1 and 4.80 nM, respectively[1].
DS88790512 is a potent, selective, and orally bioavailable TRPC6 inhibitor with an IC50 of 11 nM.
MDL 105519 is a potent and selective antagonist of glycine binding to the NMDA receptor.
Levetiracetam(UCB L059) is a novel anticonvulsant with antihyperalgesic efficacy in inflammatory pain.Target: Calcium ChannelLevetiracetam is used to control some types of seizures in patients with epilepsy. This medicine cannot cure epilepsy and will only work to control seizures for as long as you continue to use it. The exact mechanism for levetiracetam is unknown. However, the drug binds to a synaptic vesicle protein, SV2A, which is believed to impede nerve conduction across synapses [1].Levetiracetam (10-200 mg/kg), ibuprofen (12.5-100 mg/kg), celecoxib (3.75-30 mg/kg), paracetamol (50-200 mg/kg), caffeine (15-100 mg/kg), and 2-drug combinations of levetiracetam with analgesics/caffeine produced a significant, dose-dependent reduction of inflammatory hyperalgesia. Isobolographic analysis revealed that levetiracetam exerts a synergistic interaction with analgesics, with approximately 7-, 9-, and 11-fold reduction of doses of both drugs in combination of levetiracetam with paracetamol, celecoxib, and ibuprofen, respectively. Analysis of the log dose-response curves for levetiracetam (1-50 mg/kg) in the presence of caffeine (10 mg/kg) and levetiracetam applied alone also revealed a synergistic interaction. Levetiracetam's ED50 in the presence of caffeine was reduced approximately 11-fold [2].Clinical indications: Epilepsy; Social phobiaFDA Approved Date: November 2008Toxicity: depression; hallucinations; suicidal thoughts
Azumolene (EU4093 free base), a Dantrolene analog, is a muscle relaxant. Azumolene is a ryanodine receptor (RyR) modulator and inhibits the calcium-release through ryanodine receptor. Azumolene can be used for malignant hyperthermia research[1][2].
TC-I 2014 (compound 5) is a potent Benzimidazole-containing transient receptor potential melastatin 8 (TRPM8) antagonist, with IC50 values of 0.8 nM, 3.0 nM and 4.4 nM for canine, human and rat channels respectively. TC-I 2014 exhibits antiallodynic properties in pain models[1].
GNE-9278 is a highly selective positive allosteric modulator of NMDAR that acts at the GluN1 transmembrane domain (TMD). GNE-9278 acts on activated NMDARs to increase peak current and agonist affinity[1].
UBP710 is a selective NMDA receptor modulator. UBP710 displays greater activity in potentiating GluN2B-containing receptors than those containing GluN2A[1].