Jujuboside A is a glycoside extracted from Semen Ziziphi Spinosae, a Chinese herbal medicine used to treat insomnia and anxiety.
Fipronil is an insecticide that acts as a selective antagonist of insect GABA receptors (IC50s = 30 nM and 1,600 nM for cockroach and rat receptors, respectively). Fipronil also inhibits desensitizing and non-desensitizing glutamate-induced chloride currents in cockroach neurons (IC500s = 800 nM and 10 nM, respectively). Fipronil induces activity of the cytochrome P450 (CYP) isoforms CYP1A1/2, CYP2B1/2, and CYP3A1/2 in isolated rat liver microsomes.
Icilin(AG 3-5) is a synthetic super-agonist of TRPM8 ion channel.IC50 value:Target: TRPM8in vitro: icilin, a super-cooling agent, down-regulated the expression of cell cycle signature genes and caused G1 arrest in PC-3 prostate cancer cells. icilin affected cell cycle-related transcriptional modules and identified E2F1 transcription factor as a target master regulator of icilin. icilin reduced the activity and expression levels of E2F1 [1]. Icilin concentration-response curves were significantly shifted to the right when pH was lowered from 7.3 to 6.9, whereas those with menthol were unaltered in solutions of pH 6.1 [2]. Icilin modulated the expression level of various cell cycle regulators at transcription or post-translational levels. In addition, icilin activated JNK and p38 kinase pathways, but not ERK [4].in vivo: Rats injected with icilin (0.5, 1, 2.5, 5mg/kg, i.p.) displayed dose-related WDS that were inhibited by pretreatment with a fixed dose of clonidine (0.15 mg/kg, s.c.). Shaking behavior caused by a fixed dose (2.5mg/kg) of icilin was also inhibited in a dose-related manner by clonidine pretreatment (0.03-0.15 mg/kg, s.c.) and reduced by clonidine posttreatment (0.15 mg/kg, s.c.) [3].
Pepluanin A is a natural compound isolated from Euphorbia peplus L. Pepluanin A shows a very high activity for a jatrophane diterpene, outperforming Cyclosporin A by a factor of at least 2 in the inhibition of Pgp-mediated Daunomycin (HY-13062A) transport[1]
Catestatin is a 21-amino acid residue, cationic and hydrophobic peptide. Catestatin is an endogenous peptide that regulates cardiac function and blood pressure[1]. Catestatin is a non-competitive nicotinic antagonist acting through nicotinic acetylcholine receptors (nAChRs) to inhibit catecholamine release[2].
PG01 is a potent CFTR Cl- channel potentiator. PG01 can correct gating defects of CFTR mutants, is effective on b>E193K, G970R and G551D (CFTR mutants) with Kd values of 0.22 μM, 0.45 μM and 1.94 μM, respectively. PG01 is also effective on ΔF508 (Ka of 0.3 μM). PG01 increases ΔF508-CFTR Cl- current after adding Forskolin[1][2].
Piracetam is a cyclic derivative of the neurotransmitter gamma-aminobutyric acid (GABA), used in treatment of a wide range of cognitive disorders.Target: OthersPiracetam is able to significantly decrease the fusogenic and destabilising effect of Abeta 29-42, in a concentration-dependent manner. Preincubation of piracetam, at a piracetam/peptide ratio of 960, during 20 min before the addition of Abeta 29-42 prevents almost completely the mixture of the two fluorescent probes. Preincubation of piracetam with lipids prevents almost completely the release of calcein induced by the peptide in a dose-dependent fashion (piracetam/peptide ratios from 9.6 to 960) [1]. Piracetam (< 1.0 mM) preincubated with brain membranes enhances membrane fluidity in aged mice, rats and humans, as indicated by decreased anisotropy of the membrane-bound fluorescence probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Piracetam (300 mg/kg once daily) significantly increases membrane fluidity in some brain regions of young and aged rats, but has no measurable effect on membrane fluidity in the young rats [2]. Piracetam (300 mg/kg daily for 6 weeks) improves active avoidance learning in the aged rats only and elevates membrane fluidity in all brain regions except the cerebellum in the aged rats. Piracetam (300 mg/kg daily for 6 weeks) also improves NMDA receptor density in the hippocampus and on muscarinic cholinergic receptor densities in the frontal cortex and the striatum and to a lesser extent in the hippocampus of rats [3].
Orphenadrine citrate is a NMDA receptor antagonist with Ki of 6.0 +/- 0.7 μM, HERG potassium channel blocker.Target: NMDA ReceptorOrphenadrine has been used as an antiparkinsonian, antispastic and analgesic drug. Orphenadrine inhibits [3H]MK-801 binding to the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA)-receptor in homogenates of postmortem human frontal cortex with a Ki-value of 6.0 +/- 0.7 microM. The NMDA receptor antagonistic effects of orphenadrine were assessed using concentration- and patch-clamp techniques on cultured superior colliculus neurones. Orphenadrine blocked open NMDA receptor channels with fast kinetics and in a strongly voltage-dependent manner. The IC50-value against steady state currents at -70 mV was 16.2 +/- 1.6 microM (n = 6). Orphenadrine exhibited relatively fast, concentration-dependent open channel blocking kinetics (Kon 0.013 +/- 0.002 10(6) M-1S-1) whereas the offset rate was concentration-independent (Koff 0.230 +/- 0.004 S-1) [1]. Orphenadrine competitively inhibited [3H]nisoxetine binding in rat vas deferens membranes (Ki = 1.05+/-0.20 microM). It can be concluded that orphenadrine, at low micromolar concentrations, interacts with the noradrenaline reuptake system inhibiting its functionality and thus potentiating the effect of noradrenaline [2].
Almokalant is a class III antiarrhythmic drug, acts as a potassium channel blocker, and inhibits a specific component (Ikr) of the time-dependent delayed rectifier K+ current.
Chebulinic acid is a potent natural inhibitor of M. tuberculosis DNA gyrase, also can inhibit SMAD-3 phosphorylation, inhibit H+ K+-ATPase activity.
Soraprazan is a reversible, and fast-acting inhibitor of gastric H+/K+ ATPase.
Zorevunersen sodium is an antisense oligonucleotide that is intended to increase the level of productive SCN1A mRNA and consequently increase the expression of the sodium channel Nav1.1 protein. Zorevunersen sodium is used for the study of Dravet syndrome.
Trifluoperazine-d3 (dihydrochloride) is deuterium labeled Trifluoperazine (dihydrochloride). Trifluoperazine dihydrochloride, an antipsychotic agent, acts by blocking central dopamine receptors. Trifluoperazine dihydrochloride is a potent α1-adrenergic receptor antagonist. Trifluoperazine dihydrochloride is a potent NUPR1 inhibitor exerting anticancer activity. Trifluoperazine dihydrochloride is a calmodulin inhibitor, and also inhibits P-glycoprotein. Trifluoperazine dihydrochloride can be used for the research of schizophrenia. Trifluoperazine dihydrochloride acts as a reversible inhibitor of influenza virus morphogenesis[1][2][3][4][5].
Mibefradil dihydrochloride is a calcium channel blocker with moderate selectivity for T-type Ca2+ channels displaying IC50s of 2.7 μM and 18.6 μM for T-type and L-type currents, respectively.
Pantoprazole sodium hydrate is a proton pump inhibitor drug used for short-term treatment of erosion and ulceration of the esophagus caused by gastroesophageal reflux disease.IC50 value:Target: proton pump inhibitor
BTB06584 is an IF1-dependent selective inhibitor of the mitochondrial F1Fo-ATPase.Target: ATPasein vitro: BTB06584 inhibits F1Fo-ATPase activity with no effect on ΔΨm or O2 consumption. ATP consumption was decreased following inhibition of respiration, and ischaemic cell death was reduced. BTB06584 efficiency was increased by IF1 overexpression and reduced by silencing the protein. BTB06584 may represent a valuable tool to selectively inhibit mitochondrial F1Fo-ATPase activity without compromising ATP synthesis and to limit ischaemia-induced injury caused by reversal of the mitochondrial F1Fo-ATPsynthase.in vivo: BTB06584 rescues defective haemoglobin synthesis in zebrafish pinotage (pnt) mutants in which expression of the Atpif1a gene is lost.
Nisoxetine hydrochloride is a potent and selective inhibitor of noradrenaline transporter (NET), with a Kd of 0.61 nM. Nisoxetine hydrochloride is an antidepressant and local anesthetic, it can block voltage-gated sodium channels[1][2][3].
Nitrendipine is a calcium channel blocker with marked vasodilator action.Target: Calcium ChannelNitrendipine is a dihydropyridine calcium channel blocker. It is used in the treatment of primary hypertension to decrease blood pressure. Nitrendipine blocked Ca2+ currents very potently, with half-block by subnanomolar concentrations. The concentration dependence of block had the form expected for 1:1 binding, with an apparent dissociation constant (Kd) of 0.36 nM. In contrast, when cells were held at hyperpolarized potentials, nitrendipine blocked Ca2+ currents much less potently (Kd approximately equal to 700 nM) [1, 2]. Nitrendipine, a potent analogue of nifedipine, binds in a reversible and saturable manner to partially purified guinea-pig heart membranes [3]. [3H]nitrendipine binding in smooth muscle is to a site which mediates the pharmacologic response [4].
α7 nAchR-JAK2-STAT3 agonist 1 is a potent α7 nAchR-JAK2-STAT3 agonist, with an IC50 value of 0.32 μM for nitric oxide (NO). α7 nAchR-JAK2-STAT3 agonist 1 effectively suppresses the expression of iNOS, IL-1β, and IL-6 in murine RAW264.7 macrophages. α7 nAchR-JAK2-STAT3 agonist 1 can inhibit LPS-induced NO release, NF-κB activation and cytokine production. α7 nAchR-JAK2-STAT3 can be used for researching sepsis[1].
(±)-Epibatidine is a nicotinic agonist. (±)-Epibatidine is a neuronal nAChR agonist.
(Thr4,Gly7)-Oxytocin, an Oxytocin analogue, is a specific OT receptor agonist. (Thr4,Gly7)-Oxytocin also excites subicular neurons via activation of TRPV1 channels, and depression of K+ channels. [1][2].
A-839977 is a novel and selective P2X7 antagonist; blocks BzATP-evoked calcium influx at recombinant human, rat and mouse P2X7 receptors (IC50 values are 20, 42 and 150 nM respectively).IC50 Value: Target: P2X7in vitro: A-839977 potently (IC50=20-150 nM) blocked BzATP-evoked calcium influx at recombinant human, rat and mouse P2X7 receptors. A-839977 also potently blocked agonist-evoked YO-PRO uptake and IL-1beta release from differentiated human THP-1 cells [1]. in vivo: Systemic administration of A-839977 dose-dependently reduced thermal hyperalgesia produced by intraplantar administration of complete Freund's adjuvant (CFA) (ED50=100 micromol/kg, i.p.) in rats. A-839977 also produced robust antihyperalgesia in the CFA model of inflammatory pain in wild-type mice (ED50=40 micromol/kg, i.p.), but the antihyperalgesic effects of A-839977 were completely absent in IL-1alphabeta knockout mice [1].
Tofogliflozin(CSG-452) is a potent and highly specific sodium/glucose cotransporter 2(SGLT2) inhibitor with Ki values of 2.9, 14.9, and 6.4 nM for human, rat, and mouse SGLT2.IC50 value: 2.9/14.9/6.4 nM(human/rat/mouse SGLT2) [1]Target: SGLT2 inhibitorin vitro: Tofogliflozin competitively inhibited SGLT2 in cells overexpressing SGLT2, and K(i) values for human, rat, and mouse SGLT2 inhibition were 2.9, 14.9, and 6.4 nM, respectively. The selectivity of tofogliflozin toward human SGLT2 versus human SGLT1, SGLT6, and sodium/myo-inositol transporter 1 was the highest among the tested SGLT2 inhibitors under clinical development [1]. tofogliflozin was catalyzed to the primary hydroxylated derivative (M4) by CYP2C18, CYP4A11 and CYP4F3B, then M4 was oxidized to M1. 3. Tofogliflozin had no induction potential on CYP1A2 and CYP3A4 [4].in vivo: A single oral gavage of tofogliflozin increased renal glucose clearance and lowered the blood glucose level in Zucker diabetic fatty rats. Tofogliflozin also improved postprandial glucose excursion in a meal tolerance test with GK rats. In db/db mice, 4-week tofogliflozin treatment reduced glycated hemoglobin and improved glucose tolerance in the oral glucose tolerance test 4 days after the final administration [1]. Tofogliflozin (400 ng/ml) induced UGE of about 2 mg·kg?1·min?1 and increased EGP by 1-2 mg·kg?1·min?1, resulting in PG in the normal range [2]. Tofogliflozin suppressed plasma glucose and glycated Hb and preserved pancreatic beta-cell mass and plasma insulin levels. No improvement of glycaemic conditions or insulin level was observed with losartan treatment [3].
Microgrewiapine A is an antagonist of nAChR. Microgrewiapine A inhibits hα4β2 and hα3β4 activity with 60% and 70% inhibition, respectively. Microgrewiapine A has selective cytotoxic against HT-29 human colon cancer cells with an IC50 of 6.8 μM[1].
TAK-438 (free base) is a novel P-CAB (potassium-competitive acid blocker) that reversibly inhibits H+/K+ ATPase with IC50 of 19 nM (pH 6.5), controls gastric acid secretion.IC50 value: 19 nM [1]Target: H+/K+ ATPasein vitro: TAK-438 is a pyrrole derivative with a chemical structure that is completely different from the P-CABs developed to date. TAK-438 inhibits gastric H+/K+ ATPase activity in a concentration-dependent manner. Under neutral conditions (pH 7.5), the inhibitory activity of TAK-438 is almost the same as that under weakly acidic conditions (pH 6.5). TAK-438 does not inhibit Na+/K+ ATPase activity even at concentration 500 times higher than their IC50 values against gastric H+/K+ ATPase activity. TAK-438 inhibits gastric H+/K+ ATPase in a K+ competitive manner with Ki of 3 nM [2]. in vivo: TAK-438 inhibits basal gastric acid secretion in a dose-dependent manner, and the ID50 value is 1.26 mg/kg. Intravenous administration of TAK-438 dose-dependently increases the pH of the gastric perfusate, and the increase in pH is sustained for 5 h after administration. At the 1 mg/kg dose, the pH plateaues 90 min after administration, and the highest pH value reached is 5.9 [2]. In addition, TAK-438 shows a potent and longer-lasting inhibitory effect on the histamine-stimulated gastric acid secretion in rats and dogs. TAK-438 shows significant antisecretory activity through high accumulation and slow clearance from the gastric tissue. TAK-438 is unaffected by the gastric secretory state, unlike PPIs [3].
Evodine, the major limonoid of Evodiae Fuctus, is a potent P-gp inhibitor. Evodine has protection against glutamateinduced toxicity by preserving the antioxidant defense system[1].
Ropanicant (SUVN-911 free base) is a novel, potent, selective, and orally active neuronal nicotinic acetylcholine α4β2 receptor antagonist for the research of depression[1].
Mesoridazine (TPS-23) , a metabolite of Thioridazine (HY-B0965A), acts as an orally active phenothiazine antipsychotic agent. Mesoridazine is a potent and rapid open-channel blocker of human ether-a-go-go related gene (hERG) channels and blocks hERG currents with an IC50 of 550 nM (at 0 mV) in human embryonic kidney 293 cells[1].Mesoridazine can be used for the research of schizophrenia, as well as certain other psychiatric disorders[1][2].
MRZ 2-514 is an antagonist of the strychnine-insensitive modulatory site of the NMDA receptor (glycineB), with Ki of 33 μM.
7ACC2 is a new potent MCT inhibitor with IC50 of 11 nM for inhibition of [14C]-lactate influx; new antitumor treatment targeting lactate transport in cancer cells.IC50 value: 11 nM ([14C]-lactate influx) [1]Target: MCT inhibitor; lactate transport inhibitor7ACC2 did not influence the prothrombin time which, together with a good in vitro ADME profile, supports the potential of this new family of compounds to act as anticancer drugs through inhibition of lactate flux.