(+)-Tetrabenazine D6 is the deuterium labeled (+)-Tetrabenazine. (+)-Tetrabenazine is a reversible inhibitor of vesicular monoamine transporter 2 (VMAT-2).
Carbamazepine, a sodium channel blocker, is an anticonvulsant drug.Target: Sodium channelCarbamazepine inhibits the binding of [3H]batrachotoxinin A 20-α-benzoate (BTX-B) to a receptor site of voltage-sensitive sodium channel with IC50 of 131 μM, to decrease the activation of sodium channel ion flux in rat brain synaptosomes. Carbamazepine does not alter basal 125I-labeled scorpion toxin binding to synaptosomes in the absence of batrachotoxin, but when batrachotoxin (1.25 μM) added, Carbamazepine inhibits the batrachotoxin-dependent increase in scorpion toxin binding in a concentration-dependent manner with IC50 of 260 μM mediated at the alkaloid toxin binding site, none of which affects [3H]saxitoxin binding [1]. Carbamazepine at 25 mg/kg significantly increases extracellular levels of striatal and hippocampal dopamine (DA), 3,4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in a dose dependent manner, while Carbamazepine at 50 mg/kg significantly decreases total levels of striatal DA and DOPA as well as hippocampal HVA, but has no effect on total levels of striatal DOPAC and HVA nor on hippocampal DA, DOPA and DOPAC [2].
DPI 201-106 (SDZ 201106) is a cardiotonic agent with a synergistic sarcolemmal and intracellular mechanism of action. DPI 201-106 shows cardioselective modulation of voltage-gated sodium channels (VGSCs) resulting in a positive inotropic effect[1][2][3].
BPDBA is a selective and noncompetitive betaine/GABA transporter (BGT-1) inhibitor with IC50s of 20 μM and 35 μM against human BGT-1 and mouse GAT2, respectively[1].
SKA-121 is a selective KCa3.1 activator. SKA-121 exhibits EC50s of 109 nM and 4.4 μM for KCa3.1 and KCa2.3, respectively.
SRI-41315 is a small molecule that induces translational readthrough of CFTR nonsense mutations by eRF1 depletion, restores CFTR expression and function, suppresses CFTR nonsense mutations.SRI-41315 induces translational readthrough by depleting eRF1 protein level and prolonging the translational pause that occurs at premature termination codons (PTCs).SRI-41315 reduced eRF1 levels in a manner dependent upon a ubiquitin-mediated proteasome degradation pathway.SRI-41315 in combination with G418 restores CFTR function in primary bronchial epithelial cells derived from a CF patient with CFTR nonsense alleles.
KPT-185 is an orally bioavailable selective inhibitor of CRM1 amd displayes potent antiproliferative properties at submicromolar concentrations (IC50 values:100-500nM), induced apoptosis (average 5-fold increase), cell-cycle arrest, and myeloid differentiation in AML cell lines and patient blasts.IC50 value: 100-500 nM (AML cell lines) [1]Target: CRM1in vitro: Submicromolar concentrations of KPT-185 inhibited leukemia cell proliferation, with IC50 values ranging from 100nM to 500nM (MV4-11, Kasumi-1, OCI/AML3, MOLM-13, KG1a, and THP-1). KPT-185 at the predetermined IC50 value induced cell-cycle arrest at G1 with respect to vehicle-treated-control (DMSO) in MV4-11 (82.2% ± 3.69% vs 71.55% ± 0.21%, P < .01), OCI/AML3 (83.05% ± 6.84% vs 55.1% ± 2.26%, P < .01), and MOLM-13 (82.72% ± 1.14% vs 57.55 ± 3.46%, P < .01) cells at 24 hours. A significant accumulation of p53 in the nucleus of MV4-11 and OCI-AML3 was observed after treatment with KPT-185 [1]. KPT-185 also induced CRM1 accumulation in the nucleus, resulting in CRM1 degradation by the proteasome [2]. in vivo: In melanoma xenograft models, CRM1 inhibition reduces tumor growth independent of BRAF or NRAS status and induces complete regression of BRAF V600E tumors when combined with BRAF inhibition [3].
Meclofenoxate hydrochloride, an ester of dimethylethanolamine (DMAE) and 4-chlorophenoxyacetic acid (pCPA), has been shown to improve memory, have a mentally stimulating effect, and improve general cognition.IC50 value: Target: nootropicMeclofenoxate, administered in a dose of 50 mg/kg twice daily for 7 days using the maze-training method, increased the number of responses to the conditioned stimulus, when retention tests were made 24 hours and 7 days after training, whereas citicholine, applied in the same way in a dose of 10 mg/kg, shortened the latency of the responses with reinforcement during the training and increased the number of correct responses to the conditioned stimulus in retention tests 7 days after the training [1]. Meclofenoxate appears to increase the consolidation of new information into long-term memory, but does not affect other aspects of remembering [2].
Ginsenoside Rd inhibits TNFα-induced NF-κB transcriptional activity with an IC50 of 12.05±0.82 μM in HepG2 cells. Ginsenoside Rd inhibits expression of COX-2 and iNOS mRNA. Ginsenoside Rd also inhibits Ca2+ influx. Ginsenoside Rd inhibits CYP2D6, CYP1A2, CYP3A4, and CYP2C9, with IC50s of 58.0±4.5 μM, 78.4±5.3 μM, 81.7±2.6 μM, and 85.1±9.1 μM, respectively.
Venturicidin A (Aabomycin A1), from actinomycetes, is a membrane-active natural product inhibitor of ATP synthase. Venturicidin A potentiates the aminoglycoside antibiotic gentamicin against multidrug-resistant clinical isolates of Staphylococcus, Enterococcus, and Pseudomonas aeruginosa. Venturicidin A shows noticeable toxicity toward human embryonic-kidney (HEK)cells with an IC50 of 31 μg/mL[1].
Eliprodil(SL-820715) is a non-competitive NR2B-NMDA receptor antagonist(IC50=1 uM), less potent for NR2A- and NR2C-containing receptors(IC50> 100 uM).IC50 value:Target: NR2B-NMDA antagonistHuman N-type Ca2+ channel currents were inhibited by ifenprodil and eliprodil with IC50 values of 50 microM and 10 microM respectively whereas P-type Ca2+ channel currents were inhibited reversibly by ifenprodil and eliprodil with approximate IC50 values of 60 microM and 9 microM respectively. eliprodil (1 microm) produced a moderate reverse rate-dependent prolongation of the action potential duration (7.4+/-1.5, 8.9+/-2.1 and 9.9+/-1.8% at cycle lengths of 300, 1000 and 5000 ms, respectively; n=9).
GlyH-101 is a cell-permeable glycinyl hydrazone compound that blocks CFTR with Ki of 1.4 uM.IC50 value: 1.4 uM (Ki, at +60 mV) [1]Target: CFTRin vitro: GlyH-101 reversibly inhibited CFTR Cl- conductance in <1 min. Whole-cell current measurements revealed voltage-dependent CFTR block by GlyH-101 with strong inward rectification, producing an increase in apparent inhibitory constant Ki from 1.4 microM at +60 mV to 5.6 microM at -60 mV. GlyH-101 inhibitory potency was independent of pH from 6.5-8.0, where it exists predominantly as a monovalent anion with solubility approximately 1 mM in water[1]. In HeLa cells, these events were associated with a decrease in the rate of oxygen consumption, with GlyH-101 demonstrating a higher potency than CFTR(inh)-172. The impact of CFTR inhibitors on inflammatory parameters was also tested in HeLa cells. CFTR(inh)-172, but not GlyH-101, induced nuclear translocation of nuclear factor-kappaB (NF-kappaB) [2]. GlyH-101 is a glycine hydrazide that has recently been shown to block CFTR channels but its effects on cardiomyocytes are unknown. Here the action of GlyH-101 on cardiac I(Cl.PKA) and on other ion currents has been established. Whole-cell patch-clamp recordings were made from rabbit isolated ventricular myocytes. GlyH-101 blocked I(Cl.PKA) in a concentration- and voltage-dependent fashion (IC(50) at +100 mV=0.3 ± 1.5 μM and at -100 mV=5.1 ± 1.3 μM) [3].in vivo: Topical GlyH-101 (10 microM) in mice rapidly and reversibly inhibited forskolin-induced hyperpolarization in nasal potential differences. In a closed-loop model of cholera, intraluminal GlyH-101 (2.5 microg) reduced by approximately 80% cholera toxin-induced intestinal fluid secretion [1].
Tocainide hydrochloride is an orally activesodium channel blocker, it blocks the sodium channels in the pain-producing foci in the nerve membranes. Tocainide hydrochloride is a primary amine analog of lidocaine, can be used for the treatment of tinnitus[1][2].
AS1928370 (ASP8370) is a potent, selective, orally available TRPV1 antagonist with IC50 of 0.51 uM, shows no inhibitory effects on TRPV4, TRPA11, and TRPM8 at 10 uM; demonstrates high aqueous solubility (pH6.8, >100 uM), satisfactory stability in human liver microsomes, and reduced CYP3A4 inhibition; improves capsaicin-induced secondary hyperalgesia and mechanical allodynia in an L5/L6 spinal nerve ligation model in rats with respective ED50s of 0.17 and 0.26 mg/kg p.o.
SUVN-911 is a potent, selective, brain penetrated and orally bioavailable neuronal nicotinic acetylcholine α4β2 receptor antagonist, with a Ki of 1.5 nM. SUVN-911 has antidepressant activity[1].
Clofilium tosylate, a potassium channel blocker, induces apoptosis of human promyelocytic leukemia (HL-60) cells via Bcl-2-insensitive activation of caspase-3. Antiarrhythmic agent[1].
Abecarnil (ZK 112119) is a ligand or a partial agonist for benzodiazepine (BZ) receptor. Abecarnil possesses anxiolytic and anticonvulsant properties. Abecarnil can act as a positive allosteric modulator of GABAA receptor. Abecarnil inhibits the binding of the BZ [3H]lormetazepam to rat cerebral cortex membranes, with an IC50 of 0.82 nM. Abecarnil can be used for epilepsy research[1][2][3][4].
TRPM8-IN-1 (example 14) is an inhibitor of transient receptor potential melastatin-8 (TRPM8) channels, IC50<5 μM[1].
Ivacaftor is a potent and orally bioavailable CFTR potentiator, targeting G551D-CFTR and F508del-CFTR with EC50s of 100 nM and 25 nM, respectively.
CFTR corrector 4 (Compound 13), an active (R,R)-form enantiomer, is a highly potent and orally active cystic fibrosis transmembrane conductance regulator (CFTR) corrector. CFTR corrector 4 can increase CFTR levels at the cell surface and have the potential for treatment of cystic fibrosis[1].
DSP-2230 is a selective Nav1.7/Nav1.8 blocker[1][2].
CALP1 is a calmodulin (CaM) agonist (Kd of 88 µM) with binding to the CaM EF-hand/Ca2+-binding site. CALP1 blocks calcium influx and apoptosis (IC50 of 44.78 µM) through inhibition of calcium channel opening. CALP1 blocks glutamate receptor channels and blocks a store-operated nonselective cation channel. CALP1 activates CaM-dependent phosphodiesterase activity[1][2][3][4].
(S)-(-)-5-Fluorowillardiine Hcl is a potent and specific AMPAR agonist.
Dimethyl lithospermate B (dmLSB) is a selective Na+ channel agonist. Dimethyl lithospermate B slows inactivation of sodium current (INa), leading to increased inward current during the early phases of the action potential (AP)[1][2].
JAMI1001A is a positive allosteric modulator of AMPA receptor. JAMI1001A efficaciously modulates AMPA receptor deactivation and desensitization of both flip and flop receptor isoforms[1].
Pandinotoxin Kα, isolated from the venom of Pandinus imperator, is the inhibitor of A-type potassium channel[1].
MRK-016 is a selective, orally bioavailable inverse agonist of GABAA α5 receptor, with an EC50 of 3 nM for GABAA α5, and Kis of 0.83, 0.85, 0.77 and 1.4 nM for human GABAA α1β3γ2, GABAA α2β3γ2, GABAA α3β3γ2, and GABAA α5β3γ2, respectively; MRK-016 also readily penetrates the CNS.
4-Bromo A23187 is a halogenated analog of the highly selective calcium ionophore A-23187. 4-Bromo A23187，a calcium modulator, induces apoptosis in different cells, including HL-60 cells[1].
DQP-26 is a potent NMDAR negative allosteric modulator with IC50 values of 0.77 μM and 0.44 μM for GluN2C and GluN2D, respectively. DQP-26 has the potential for NMDAR-associated neurological disease research[1].