SCH-23390-d3 (R-(+)-SCH-23390-d3) hydrochloride is the deuterium labeled SCH-23390 hydrochloride. SCH-23390 hydrochloride (R-(+)-SCH-23390 hydrochloride) is a potent and selective dopamine D1-like receptor antagonist with Kis of 0.2 nM and 0.3 nM for the D1 and D5 receptor, respectively. SCH-23390 hydrochloride is a potent and high efficacy human 5-HT2C receptor agonist with a Ki of 9.3 nM. SCH-23390 hydrochloride also binds with high affinity to the 5-HT2 and 5-HT1C receptors. SCH-23390 hydrochloride inhibits G protein-coupled inwardly rectifying potassium (GIRK) channels with an IC50 of 268 nM[1][2][3].
trans-Ned 19, a NAADP antagonist and TPC blocker, suppresses the calcium signal in human umbilical vein endothelial cells (HUVEC) and the rat aorta relaxation in response to low histamine concentrations[1].
α5IA (L-822179) is a selective α5 GABAA receptor inverse agonist with neuroprotective potential[1].
(-)-Praeruptorin A is a nature product that could be isolated from the roots of Peucedanum praeruptorum Dunn. (-)-Praeruptorin A relaxes ileum and tracheal smooth muscles by activating NO/cGMP signaling pathway. (-)-Praeruptorin A has dramatically therapeutic effects on hypertension mainly through acting as a Ca2+-influx blocker[1].
Triciribine phosphate (TCN-P) inhibits amidophosphoribosyltransferase by an allosteric mechanism which affects the first committed step of de novo purine biosynthesis. Triciribine phosphate also inhibits IMP dehydrogenase which is the first committed step of guanosine nucleotide synthesis. Tricilibine phosphate does not affect ligase activity[1].
Taspine is a natural product with anti-inflammatory activity. Taspine suppresses P2X4 receptor activity via PI3K inhibition. Taspine inhibits pro-inflammatory signalling via inhibition of P2X4 receptors in macrophage[1].
1-Aminocyclobutanecarboxylic acid is a NMDA receptor partial agonist acting at the glycine site, NR1[1].
Becampanel (AMP397) is the first competitive AMPA antagonist and an antiepileptic agent.
Linalool-d3 is the deuterium labeled Linalool[1]. Linalool is natural monoterpene in essential olis of coriander, acts as a competitive antagonist of Nmethyl d-aspartate (NMDA) receptor, with anti-tumor, anti-cardiotoxicity activity[2].Linalool is a PPARα ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome[3].
Rostafuroxin(PST 2238) is a antihypertensive compound; Na,K-ATPase antognist;displaced [3H]ouabain from the dogkidney Na+,K+-ATPase with IC50 of 1.5 nM.IC50 value: 1.5 nM [1]Target: Na+,K+-ATPase modulator; ouabain antagonistin vitro: PST 2238 displaced [3H]ouabain from the dog kidney Na+,K+-ATPase receptor (IC50 ) 1.5X 10-6M), was devoid of cardiac inotropic activity in isolated guinea pig atria, and showed no affinity up to 10-4 M with general (R1, R2, a1, a2, A1, A2, M1, M2, H1, H2, 5-HT1, 5-HT2, Ca2+ channels, TXA2/PGH2, PAF, GABAA, GABAB, DA-NE-5-HT uptake, glutammate,glycine, benzodiazepine) and hormonal (estrogenic, progestinic, androgenic, mineralcorticoid) receptors [1]. At molecular level, in the kidney, Rostafuroxin antagonizes EO triggering of the Src-epidermal growth factor receptor (EGFr)-dependent signaling pathway leading to renal Na+-K+ pump, and ERK tyrosine phosphorylation and activation [3].in vivo: PST 2238, given orally at very low doses (1 and 10 microg/kg for 5-6 weeks), reduced the development of hypertension in MHS rats and normalized the increased renal Na,K-ATPase activity and mRNA levels, whereas it did not affect either blood pressure or Na,K-ATPase in Milan-normotensive (MNS) rats [2].
ML204 is a novel potent antagonist that selectively modulates native TRPC4/C5 ion channels.IC50 value:Target: TRPC4/C5 inhibitorML204 inhibited TRPC4β-mediated intracellular Ca(2+) rise with an IC(50) value of 0.96 μm and exhibited 19-fold selectivity against muscarinic receptor-coupled TRPC6 channel activation. In whole-cell patch clamp recordings, ML204 blocked TRPC4β currents activated through either μ-opioid receptor stimulation or intracellular dialysis of guanosine 5'-3-O-(thio)triphosphate (GTPγS), suggesting a direct interaction of ML204 with TRPC4 channels rather than any interference with the signal transduction pathways. Selectivity studies showed no appreciable block by 10-20 μm ML204 of TRPV1, TRPV3, TRPA1, and TRPM8, as well as KCNQ2 and native voltage-gated sodium, potassium, and calcium channels in mouse dorsal root ganglion neurons. In isolated guinea pig ileal myocytes, ML204 blocked muscarinic cation currents activated by bath application of carbachol or intracellular infusion of GTPγS, demonstrating its effectiveness on native TRPC4 currents [1]. ML204 blocked TRPC4 channels in an electrophysiological assay with an IC value of 2.6 μM and was also active in fluorescent and electrophysiological assays in which TRPC4 channels were activated by different mechanisms, indicating direct block of TRPC4 channels. Selectivity for block of TRPC4 channels was examined in fluorescent and electrophysiological experiments against closely related TRPC channels and more distantly related TRPV, TRPA and TRPM channels, and against non-TRP ion channels. ML204 afforded good selectivity (19-fold) against TRPC6 channels and more modest selectivity against TRPC3 and TRPC5 (9-fold) channels [2].
Isotachysterol 3 is an analog of 1,25-dihydrox Vitamin D3. Isotachysterol 3 stimulates intestinal calcium transport and bone calcium mobilization in anephric rats[1].
(S)-Dinotefuran ((S)-MTI-446), a neonicotinoid pesticide, is toxic by binding to α8 subunit of nAChR of honeybee Apis mellifera (Apis mellifera Linnaeus). (S)-Dinotefuran shows more toxic than R-dinotefuran to honeybee Apis mellifera[1].
Verdinexor(KPT-335) is a novel, orally bioavailable selective inhibitor of nuclear export (SINE), inhibits nuclear export protein Exportin 1(XPO1/CRM1) against canine tumor cell lines; also reduce influenza virus replication in vitro and in vivo.IC50 value:Target: SINE; XPO1/CRM1in vitro: potently and selectively inhibit vRNP export and effectively inhibited the replication of various influenza virus A and B strains in vitro, including pandemic H1N1 virus, highly pathogenic H5N1 avian influenza virus, and the recently emerged H7N9 strain [1]. KPT-335 inhibited proliferation, blocked colony formation, and induced apoptosis of treated cells at biologically relevant concentrations of drug. Additionally, KPT-335 downregulated XPO1 protein while inducing a concomitant increase in XPO1 messenger RNA. Lastly, KPT-335 treatment of cell lines upregulated the expression of both protein and mRNA for the tumor suppressor proteins p53 and p21, and promoted their nuclear localization [3].in vivo: Prophylactic and therapeutic administration of verdinexor protected mice against disease pathology following a challenge with influenza virus A/California/04/09 or A/Philippines/2/82-X79, as well as reduced lung viral loads and proinflammatory cytokine expression, while having minimal toxicity [1]. A dose expansion study was performed in 6 dogs with NHL given 1.5 mg/kg KPT-335 Monday/Wednesday/Friday; CB was observed in 4/6 dogs with a median TTP for responders of 83 days (range 35-354 days). Toxicities were primarily gastrointestinal consisting of anorexia, weight loss, vomiting and diarrhea and were manageable with supportive care, dose modulation and administration of low dose prednisone; hepatotoxicity, anorexia and weight loss were the dose limiting toxicities [2]. Inhibition of XPO1 with KPT-335 attenuated cyst growth in vivo in the PKD1 mutant mouse model Pkd1v/v [4].
Capsazepine is a synthetic analogue of the sensory neurone excitotoxin, and an antagonist of TRPV1 receptor with an IC50 of 562 nM.
Zatebradine(UL-FS49) Hcl is a potent HCN channels antagonist, which decreased the heartbeat in a reversible manner; 92% inhibition of the hHCN1-mediated current at 10 uM.IC50 value: 10 uM(92% 92% inhibition of the hHCN1) [1]Target: hHCN channel antagonistThe pharmacological properties of hHCN1-mediated currents resembled those of native hyperpolarization-activated currents (I(h)), that is, blockade by Cs(+) (99% at 5 mm), ZD 7288 (98% at 100 microm) and zatebradine (92% at 10 microm) [1]. When voltage-clamp pulse trains were applied, cilobradine induced a use-dependent blockade of If that was stronger and faster than that with zatebradine. Recovery from blockade during prolonged hyperpolarization was significantly faster with zatebradine [2]. The selective HCN blocker zatebradine reduced the activity of oriens-lacunosum moleculare interneurons in wild-type but not HCN2(-/-) mice and decreased the frequency of spontaneous inhibitory currents in postsynaptic CA1 pyramidal cells [3].
Ralfinamide (FCE-26742A) is an orally available Na(+) channel blocker derived from α-aminoamide, with function of suppressing pain[1].
CLP290 is an orally available activator of the neuron-specific K+-Cl− cotransporter KCC2, displays potential for treatment of a wide range of neurological and psychiatric indications. CLP290 can significantly lower blood arginine-vasopressin (AVP) and glucose levels in STZ rats[1][2].
A-887826 is a potent, selective, oral bioavailable and voltage-dependent Na(v)1.8 sodium channel blocker with an IC50 of 11 nM . A-887826 attenuates neuropathic tactile allodynia in vivo[1].
SL651498 is a full agonist of α2 and α3 GABAA receptors, and a partial agonist of α1 and α5 GABAA receptors. SL651498 shows anxiolytic and anticonvulsant activities[1].
ATX-II is a specific Na+ channel Modulator toxin that can be isolated from the venom of sea anemone (Anemonia sulcata). ATX-II causes delayed inactivation of the Na+HY-B1010), Caffeine, and Ryanodine (HY-103306). ATX-II also induces pulmonary vein arrhythmogenesis and atrial fibrillation[1][2].
Rapastinel (GLYX-13) is an N-methyl-D-aspartate receptor (NMDAR) modulator that has characteristics of a glycine site partial agonist. Target: NMDARapastinel is a robust cognitive enhancer and facilitates hippocampal long-term potentiation (LTP) of synaptic transmission in slices.
3-Aminopropylphosphinic acid (3-APPA), a phosphonic analog of GABA, is a GABAB receptor agonist[1].
Bafilomycin A1, a macrolide antibiotic isolated from the Streptomyces species, is a specific inhibitor of vacuolar-type H+ ATPase.
Azosemide, a sulfonamide loop diuretic, is a potent NKCC1 inhibitor with IC50s of 0.246 µM and 0.197 µM for hNKCC1A and NKCC1B, respectively[1].
Farnesyl pyrophosphate, a 15-carbon isoprenoid, is a metabolic intermediate of the mevalonate (MVA) pathway. Farnesyl pyrophosphate is a TRPM2 (TRP Channel) agonist, activates TRPM2 opening for ion influx. Farnesyl pyrophosphate is a key branch substrate for cholesterol synthesis, ubiquinones synthesis, protein farnesylation decoration, and geranyl-geranyl pyrophosphate (GGPP) synthesis[1].
Fantofarone is a highly potent Calcium Channel antagonist.
NBI-98854 is a potent, highly selective, VMAT2 inhibitor that is effective in regulating the levels of dopamine release during nerve communication.IC50 value:Target: VMAT2NBI-98854 completed a Phase I single ascending dose clinical trial in healthy male volunteers in Canada under an approved Clinical Trial Application with Health Canada.This trial showed NBI-98854 to be generally safe and well tolerated.
nAChR modulator-2, a insecticide, is a insect nAChR orthosteric modulator[1].
Dapagliflozin (2S)-1,2-propanediol, hydrate is the S-enantiomer of Dapagliflozin 1,2-propanediol, hydrate. Dapagliflozin inhibits sodium/glucose cotransporter 2 (SGLT2), which results in excretion of glucose into the urine.