Amifampridine (3,4-Diaminopyridine) phosphate is an orally active potassium channel blocker (PCB), can block presynaptic potassium channels[1]. Amifampridine phosphate can be used in Lambert-Eaton myasthenic syndrome (LEMS) research[1].
Carboxyamidotriazole Orotate (L-651582 Orotate) is the orotate salt form of Carboxyamidotriazole (CAI), an orally bioavailable signal transduction inhibitor. Carboxyamidotriazole Orotate is a cytostatic inhibitor of nonvoltage-operated calcium channels and calcium channel-mediated signaling pathways. Carboxyamidotriazole Orotate shows anti-tumor, anti-inflammatory and antiangiogenic effects[1][2].
Risperidone is a serotonin 5-HT2 receptor blocker, P-Glycoprotein inhibitor and potent dopamine D2 receptor antagonist, with Kis of 4.8, 5.9 nM for 5-HT2A and dopamine D2 receptor, respectively.
Chrysosplenetin is one of the polymethoxylated flavonoids in Artemisia annua L. (Compositae) and other several Chinese herbs. Chrysosplenetin inhibits P-gp activity and reverses the up-regulated P-gp and MDR1 levels induced by artemisinin (ART). Chrysosplenetin significantly augments the rat plasma level and anti-malarial efficacy of ART, partially due to the uncompetitive inhibition effect of Chrysosplenetin on rat CYP3A[1].
RQ-00203078 is a highly selective, potent and orally available TRPM8 antagonist (IC50 values are 5.3 and 8.3 nM for rat and human channels respectively), exhibits >350-fold selectivity for TRPM8 over TRPV4, TRPV1 and TRPA1. IC50 value: 5.3 nM (for rat channel), 8.3 nM nM ( for human channel)Target: TRPM8in vitro: RQ-00203078 reduces HSC3 and HSC4 oral squamous carcinoma cell migration and invasion.in vivo: RQ-00203078 demonstrates excellent in vivo activity in a dose dependent manner with an ED50 value of 0.65 mg/kg in the icilin-induced wet-dog shakes model in rats after oral administration and may become an important pharmacological tool for fully assessing the potential therapeutic use of the targets activated by cold stimulation. RQ-00203078 also attenuates icilin-induced wet dog shakes in rats.
N-Bromoacetamide can irreversibly remove sodium channel inactivation in the cytoplasmic face of the membrane, also decreasing K current rapid inactivation[1][2].
CDN1163 is a sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activator.
Furosemide sodium (Lasix) is a loop diuretic inhibitor of Na+/2Cl-/K+ (NKCC) cotransporter of which used in the treatment of congestive heart failure and edema.Target: NKCC Furosemide (INN/BAN) or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi under the brand name Lasix, and also under the brand names Fusid and Frumex. It has also been used to prevent Thoroughbred and Standardbred race horses from bleeding through the nose during races.Along with some other diuretics, furosemide is also included on the World Anti-Doping Agency's banned drug list due to its alleged use as a masking agent for other drugs.Furosemide, like other loop diuretics, acts by inhibiting NKCC2, the luminal Na-K-2Cl symporter in the thick ascending limb of the loop of Henle. The action on the distal tubules is independent of any inhibitory effect on carbonic anhydrase or aldosterone; it also abolishes the corticomedullary osmotic gradient and blocks negative, as well as positive, free water clearance.Because of the large NaCl absorptive capacity of the loop of Henle, diuresis is not limited by development of acidosis, as it is with the carbonic anhydrase inhibitors. Additionally, furosemide is a noncompetitive subtype-specific blocker of GABA-A receptors. Furosemide has been reported to reversibly antagonize GABA-evoked currents of α6β2γ2 receptors at ?M concentrations, but not α1β2γ2 receptors. During development, the α6β2γ2 receptor increases in expression in cerebellar granule neurons, corresponding to increased sensitivity to furosemide
ω-Conotoxin MVIIC is a N- and P/Q-type Ca2+ channel blocker, significantly suppresses the 11-keto-βboswellic acid-mediated inhibition of glutamate release[1].
Isosinensetin, a polymethoxylated flavone extracted from pericarpium citri reticulatae viride, exhibits inhibition on P-glycoprotein (P-gp) in MDR1-MDCKII cells[1][2].
Encenicline hydrochloride (EVP-6124 hydrochloride) is a novel partial agonist of α7 neuronal nicotinic acetylcholine receptors (nAChRs).
Varenicline-d4 is deuterium labeled Varenicline. Varenicline (CP 526555) is a potent partial agonist for α4β2 nicotinic acetylcholine receptor (nAChR) with an EC50 value of 2.3 μM. Varenicline is a full agonist for α3β4 and α7 nAChRs with EC50 values of 55 μM and 18 μM, respectively[1]. Varenicline is a nicotinic ligand based on the structure of cytisine, has the potential for smoking cessation treatment[2].
Zinc Pyrithione is an antifungal and antibacterial agent disrupting membrane transport by blocking the proton pump.Target: Proton PumpZinc pyrithione is considered as a coordination complex of zinc. The pyrithione ligands, which are formally monoanions, are chelated to Zn 2+ via oxygen and sulfur centers. In the crystalline state, zinc pyrithione exists as a centrosymmetric dimer, where each zinc is bonded to two sulfur and three oxygen centers. In solution, however, the dimers dissociate via scission of one Zn-O bond. Zinc pyrithione, which is a dimer but is probably biologically active as a monomer, induces plasma membrane depolarization with half-maximal effect (K1/2) of about 0.3 mM [1]. Zinc pyrithione is an unusual synthetic potentiator that potently activates both heterologous and native M channels by inducing channel opening at the resting potential [2]. Zinc pyrithione rapidly accumulated in the tissues of the exposed mussels, proportionately to both exposure concentration and time. Even though the 7-d median lethal concentration (LC50) = 8.27 μM established here appears high with respect to reported ZnPT environmental concentrations, the results indicate that this biocide could represent a threat for marine organisms in coastal environments and that further investigations on its biological effects at sublethal doses are needed [3].
L-Phenylalanine is an antagonist at α2δ calcium channels with a Ki of 980 nM. IC50 Value: 980 nM [1]Target: Calcium ChannelL-Phenylalanine (LPA) is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form proteins. In the brain, L-phenylalanine is a competitive antagonist at the glycine binding site of NMDA receptor and at the glutamate binding site of AMPA receptor [2, 3]. At the glycine binding site of NMDA receptor L-phenylalanine has an apparent equilibrium dissociation constant (KB) of 573 ?M estimated by Schild regression [4] which is considerably lower than brain L-phenylalanine concentration observed in untreated human phenylketonuria [5]. L-Phenylalanine also inhibits neurotransmitter release at glutamatergic synapses in hippocampus and cortex with IC50 of 980 nM, a brain concentration seen in classical phenylketonuria, whereas D-phenylalanine has a significantly smaller effect [3].
(S)-PNU-282987 hydrochloride is an isoform of PNU-282987 (HY-12560). PNU-282987 (free base) is a potent α7 nicotinic acetylcholine receptor (nAChR) agonist with an EC50 of 154 nM. PNU-282987 (free base) is also a functional antagonist of the 5-HT3 receptor with an IC50 of 4541 nM. PNU-282987 (free base) can be used for the research of central and peripheral nervous systems[1].
Philanthotoxin 74 dihydrochloride (PhTx 74) is an AMPAR antagonist; inhibits GluR3 and GluR1 with IC50s of 263 and 296 nM, respectively.
Propafenone D5 (SA-79 D5) hydrochloride is the deuterium labeled Propafenone hydrochloride. Propafenone (SA-79) hydrochloride is a class of anti-arrhythmic medication, which treats illnesses associated with rapid heart beats such as atrial and ventricular arrhythmias[1].
CGP37157 is a potent, selective inhibitor of Na+/Ca2+ exchanger, inhibiting the Na+-induced Ca2+-release from guinea-pig heart mitochondria, with an IC50 of 0.8 μM.
Hypophyllanthin is a major lignan in Phyllanthus spp, with strong anti-inflammatory activity. Hypophyllanthin directly inhibits P-glycoprotein (P-gp) activity and did not interfere with multidrug resistance protein 2 (MRP2) activity[1][2].
Triamterene D5 is deuterium labeled Triamterene, which can block epithelial Na+ channel (ENaC) in a voltage-dependent manner, which used as a mild diuretic.
Rivanicline oxalate (RJR-2403 oxalate) is a neuronal nicotinic receptor agonist, showing high selectivity for the α4β2 subtype (Ki=26 nM); > 1,000 fold selectivity than α7 receptors(Ki= 36000 nM).
Lansoprazole Sulfide D4 is a deuterium labeled Lansoprazole Sulfide. Lansoprazole Sulfide is an active metabolite of the proton pump inhibitor Lansoprazole. Lansoprazole Sulfide is an orally active anti-TB (Mycobacterium tuberculosis) agent with IC50 values of 0.59 µM intracellularly and 0.46 µM in broth[1].
GAL-021 sulfate is a potent BKCa-channel blocker. GAL-021 sulfate inhibits KCa1.1 in GH3 cells. GAL-021 sulfate is a novel breathing control modulator that is based on selective modification of the almitrine pharmacophore. GAL-021 sulfate increases minute ventilation in rats and non-human primates[1][2].
VPC01091.4 (VPC4) is a?TRPM7?inhibitor and blocks TRPM7 current at low micromolar concentrations. VPC01091.4 is an efficacious?anti-inflammatory?agent that arrests systemic inflammation in vivo[1].
D-Cycloserine is an analog of the amino acid D-alanine.Target: AntibacterialD-Cycloserine selectively potentiated the duration of motor cortical excitability enhancements induced by anodal tDCS. D-Cycloserine alone did not modulate excitability [1]. Participants receiving d-cycloserine in addition to exposure therapy reported significantly less social anxiety compared with patients receiving exposure therapy plus placebo. Controlled effect sizes were in the medium to large range [2]. Chronic D-cycloserine significantly reduced nicotine self-administration selectively in rats with low baseline nicotine use, but was ineffective with the rats with higher levels of baseline nicotine self-administration [3].
AMG 333 is a potent and highly selective TRPM8 antagonist with an IC50 of 13 nM.
Gidazepam is an agonist of GABA receptor channels (GABA RCs).
Flufenamic acid is a non-steroidal anti-inflammatory agent, inhibits cyclooxygenase (COX), activates AMPK, and also modulates ion channels, blocking chloride channels and L-type Ca2+ channels, modulating non-selective cation channels (NSC), activating K+ channels.
QX-314 bromide is a membrane-impermeable permanently charged sodium channel blocker[1].
HsTX1, from the scorpion Heterometrus spinnifer, is a 34-residue, C-terminally amidated peptide cross-linked by four disulfide bridges. HsTX1, an the inhibitor of potassium channel, with IC50 for Kv1.3 of 12 pM inhibits TEM cell activation and attenuates inflammation in autoimmunity[1][2][3].