LY-404187 is a potent, selective and centrally active positive allosteric modulator of AMPA receptors, with the EC50s of 5.65, 0.15, 1.44, 1.66 and 0.21 µM for GluR1i, GluR2i, GluR2o, GluR3i and GluR4i, respectively. LY-404187 has therapeutic potential in a number of psychiatric disorders and neurodegenerative diseases[1][2].
PF-05241328 is a potent and selective inhibitor of human Nav1.7 voltage-dependent sodium channels (Nav1.7), with an IC50 of 31 nM.
ABCG2-IN-2 is a potent ABCG2 inhibitor with favorable oral pharmacokinetic profiles in mice. ABCG2-IN-2 can be used for the research of tumor multidrug resistance (MDR) and erythropoietic protoporphyria (EPP)[1].
20-HETE(20-hydroxy Arachidonic Acid) is a potent vasoconstrictor produced in vascular smooth muscle (VSM) cells. It depolarizes VSM by blocking the open-state probability of Ca2+-activated K+-channels.IC50 Value:Target: 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation and promote hypertension. in vitro: Addition of 20-HETE to the bath (1-100 nM), reduced the frequency of opening of the large-conductance Ca(2+)-activated K+ channel recorded using cell-attached patches on VSM [1]. In kidney, 20-HETE induces diuresis by inhibiting Na+-K+-ATPase in proximal tubules and Na+/K+/Cl+ cotransporter in the thick ascending limb of Henle's loop [2].in vivo: In Cyp4a14(-/-) mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24±1 vs. 15±1μm) and M/L (0.29±0.03 vs. 0.17±0.01) [4]. The transgenic mice had overexpressed hepatic CYP4F2, high hepatic 20-HETE and fasting plasma glucose levels but normal insulin level. The GP activity was increased and the cAMP/PKA-PhK-GP pathway was activated in the transgenic mice compared with wild-type mice [5]. Clinical trial: Mechanisms of Response to Diesel Exhaust in Subjects With Asthma. Phase not specified
Cromolyn sodium is an antiallergic drug.Target: Calcium ChannelCromolyn sodium is a chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack.Pretreatment of IIR mice with Cromolyn sodium prior to ischemia exhibited no changes of ET-1 levels, injury score and inflammation (P>0.05, PreCr vs. M groups). In conclusion, administration of Cromolyn sodium after reperfusion, but not prior to ischemia, attenuates IIRI by downregulating ET-1 and suppressing sustained MC activation [1]. cromolyn sodium has a role in the prevention of Chronic lung disease(CLD). Cromolyn sodium cannot be recommended for the prevention of CLD in preterm infants [2].
VU0810464 (VU 0810464, VU464) is a selective neuronal GIRK channels activator, displays nanomolar potency for GIRK1/2 (EC50=163 nM) and improved brain penetration; exhibits comparable efficacy and potency compared with ML297, but VU0810464 is more selective for neuronal GIRK channels (GIRK1/4 EC50>500 nM); displays >3-fold more potent on GIRK1/2-expressing HEK293 cells compared to GIRK1/4-expressing cells, as measured using a Tl+ flux assay; reduced stress-induced hyperthermia in a GIRK-dependent manner in mice, ML297, but not VU0810464, decreased anxiety-related behavior as assessed with the elevated plus maze test.
Iso-PPADS tetrasodium is a P2X-purinoceptor antagonist. Iso-PPADS tetrasodium inhibits P2X1 and P2X3 receptor with IC50s of 43 nM and 84 nM. Iso-PPADS tetrasodium is protective against ventilator-induced brain injury (VIBI)[1][2].
PNU-120596 (NSC 216666 ) is a potent and selective positive allosteric α7 nAChR modulator with an EC50 of 0.2 μM.IC50 value: 0.2 uM (EC50) [1] Target: α7in vitro: PNU-120596 increases agonist (Ach)-evoked calcium flux mediated by an engineered variant of the human α7 nAChR. PNU-120596 increases agonists (choline and ACh)-evoked currents mediated by wild-type receptors and also demonstrates a pronounced prolongation of the evoked response in the continued presence of agonist in Xenopus oocytes. PNU-120596 increases the channel mean open time ofα7 nAChRs but has no effect on ion selectivity and relatively little, if any, effect on unitary conductance. When applied to acute hippocampal slices, PNU-120596 increases the frequency of ACh-evoked GABAergic postsynaptic currents measured in pyramidal neurons; this effect is suppressed by TTX, suggesting that PNU-120596 modulates the function of α7 nAChRs located on the somatodendritic membrane of hippocampal interneurons [1]. Besides the positive modulation to α7 nAChR, PNU-120596 induces a profound retardation of the kinetics of desensitization, raising the potential of Ca2+-induced toxicity through excessive stimulation of α7 nAChR [2]. PNU-120596 causes changes in cysteine accessibility at the inner beta sheet, transition zone and agonist binding site while binding to α7 nAChR. Binding sites for PNU-120596 are not in the agonist-binding sites and PNU-120596 enhances agonist-evoked gating of nicotinic receptors by eliciting conformational effects that are similar but nonidentical to the gating conformations promoted by Ach [3].in vivo: Systemic administration of PNU-120596 (1 mg/kg) to rats improves the auditory gating deficit caused by amphetamine, a model proposed to reflect a circuit level disturbance associated with schizophrenia. [1] When administered prior to Carrageenan, 30 mg/kg PNU-1230596 significantly blunts mechanical hyperalgesia and weight bearing deficits for up to 4 hours. PNU-120596 attenuates the carrageenan-induced increase in levels of TNF-α and IL-6 within the hindpaw oedema, diclofenac only attenuated IL-6 levels. Established mechanical hyperalgesia induced by Carrageenan or CFA is also partially reversed by PNU-120596 [4].
nAChR agonist CMPI hydrochloride is a potent and selective positive allosteric modulator (PAM) of nAChR containing a α4:α4 subunit interface. nAChR agonist CMPI hydrochloride enhances the response of (α4)3(β2)2 nAChR to ACh (10 µM) with an EC50 of 0.26 µM. nAChR agonist CMPI hydrochloride has potential for the research of nicotine dependence and many neuropsychiatric conditions associated with decreased brain cholinergic activity[1][2].
Anxiolytic/nonsedative agent-1 (compound 2b) is a potent and selective GABAA agonist. Anxiolytic/nonsedative agent-1 shows appreciable affinity for the BzR in bovine brain membranes with Kis of 14, 121, 239 nM for α1β2γ2, α2β2γ2, α5β3γ2, respectively. Anxiolytic/nonsedative agent-1 shows α2 selective efficacy in vitro and anxioselective effects in vivo[1].
Nav1.7 inhibitor is a potent Nav1.7 inhibitor.IC50 value:Target: Nav1.7Preparation of sulfonamide derivatives as Nav1.7 inhibitorsBy Brown, Alan Daniel; Rawson, David James; Storer, Robert Ian; Swain, Nigel Alan From PCT Int. Appl. (2012), WO 2012007868 A2 20120119.
Fanapanel (ZK200775) is a highly selective AMPA/kainate antagonist with little activity against NMDA; have Ki values of 3.2 nM, 100 nM, and 8.5 μM against quisqualate, kainate, and NMDA, respectively.
MK-2295 (NGD-8243) is a TRPV1 antagonist. MK-2295 is an analgesic agent, and can be used for research of pain[1][2].
Hymenidin is a natural antagonist of serotonergic receptor and inhibitor of voltage-gated potassium channels. Hymenidin also induces cancer cell apoptosis[1][2][3].
Nav1.8-IN-4 (compound 9a) is a Nav1.8 channel inhibitor (IC50=0.014 μM). Nav1.8-IN-4 can be used for research on pain-related diseases[1].
Chlorahololide D is a potent and selective Potassium Channel blocker with an IC50 value of 2.7 µM. Chlorahololide D is a nature product that could be isolated from the whole plant of Chloranthus holostegius[1].
FEMA 4809 is a TRPM8 receptor agonist (EC50=0.2 nM) for use as a cooling agent. TRPM8 is the ion channel responsible for the cool perception[1].
Esomeprazole Magnesium trihydrate is a proton pump inhibitor which reduces acid secretion through inhibition of the H+ / K+ ATPase in gastric parietal cells.IC50 value:Target: proton pumpEsomeprazole sodium (Nexium) is the S-isomer of omeprazole and acts as a proton pump inhibitor and gastric antisecretory agent indicated for the short-term treatment of gastroesophageal reflux disease in patients with a history of erosive esophagitis. Esomeprazole 0.4 and 0.8 mg/mL as the sodium salt in the infusion solutions tested is chemically and physically stable for at least 2 days at room temperature and 5 days under refrigeration.
(-)-Bicuculline methobromide (l-Bicuculline methobromide) is a potent GABAA receptor antagonist. (-)-Bicuculline methobromide blocks afterhyperpolarizations (AHPs) mediated by Ca2+-activated K+ channels in various types of neurons[1].
Anagyrine is an alkaloid that has been found in L. albus and has nematocidal and anticancer activities[1].It binds to muscarinic and nicotinic acetylcholine receptors (AChRs) with IC50 values of 132 and 2096 µM respectively[2].
Hardwickiic acid ((-)-Hardwikiic acid) is an antinociceptive compound that blocks Tetrodotoxin-sensitive voltage-dependent sodium channels. Hardwickiic acid shows insecticidal activity[1][2].
L-Phenylalanine-13C9 ((S)-2-Amino-3-phenylpropionic acid-13C9) is the 13C-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].
(R)-Verapamil hydrochloride ((R)-(+)-Verapamil hydrochloride) is a P-Glycoprotein inhibitor. (R)-Verapamil hydrochloride blocks MRP1 mediated transport, resulting in chemosensitization of MRP1-overexpressing cells to anticancer drugs[1][2].
LSP-GR3 is a novel chemically-modified RNA oligonucleotides, called splice modulating oligomers (SMOs), which potently and specifically modulate GluR alternative splicing to GluR3-flip expression throughout the CNS.
KPT-330, analog of KPT-185, is an orally bioavailable selective CRM1 inhibitor.IC50 value: Target: CRM1in vitro: As the clinical candidate analog of KPT-185, KPT-330 exhibits similar effects on the viability of T-ALL cells and elicits rapid apoptotic response. KPT-330 also reduces cell growth in MOLT-4, Jurkat, HBP-ALL, KOPTK-1, SKW-3, and DND-41 cell lines, with IC50 values of 34-203 nM [1]. in vivo: KPT-330 dramatically suppresses the growth of T-ALL cells (MOLT-4) and AML cells (MV4–11) in vivo, with little toxicity to normal haematopoietic cells [1]. In SCID mice with diffuse human MM bone lesions, KPT-330 inhibits MM-induced bone lysis and prolongs survival. Moreover, KPT-330 directly impairs osteoclastogenesis and bone resorption by blocking RANKL-induced NF-κB and NFATc1, with minimal impact on osteoblasts and BMSCs [2].
TRPC3/6-IN-1 is a potent selectivity and orally active molecule blocker of the canonical transient receptor channels (TRPC3/6), has block potency for hTRPC3 and hTRPC6 with IC50 values of 1260 nM and 500 nM, respectively. TRPC3/6-IN-1 can be used for the research of chronic models of heart failure[1].
Rosiglitazone-d3 (BRL 49653-d3) is the deuterium labeled Rosiglitazone. Rosiglitazone (BRL 49653) is a selective, orally active PPARγ agonist with EC50s of 30 nM, 100 nM and 60 nM for PPARγ1, PPARγ2, and PPARγ, respectively. Rosiglitazone binds to PPARγ with a Kd of approximately 40 nM. Rosiglitazone is also an activator of TRPC5 (EC50=~30 μM) and an inhibitor of TRPM3[1][2][3][4].
SOR-C13, a carboxy-terminal truncated peptide, is a high-affinity TRPV6 antagonist with an IC50 value of 14 nM. TRPV6 is a non-voltage gated calcium channel that is associated with malignancy and poor prognosis in breast cancer. SOR-C13 has anticancer activity[1].
3-Methylglutaconic acid is the major metabolites accumulating in 3-Methylglutaconic aciduria (MGTA). 3-Methylglutaconic acid can induce lipid oxidative damage and protein oxidative. 3-Methylglutaconic acid decreases the non-enzymatic antioxidant defenses in cerebral cortex supernatants to elicit oxidative stress in the cerebral cortex. 3-Methylglutaconic acid can be used for brain damage disease research[1].
JNJ 303 is a potent IKs blocker with an IC50 value of 64 nM. JNJ 303 does not have any effects on other cardiac channels at concentrations of 3.3 μM for INa, Ica, Ito, and IKr. JNJ 303 induces QT-prolongations and causes unprovoked torsades de pointes (TdP)[1].