Adiphenine HCl is a nicotinic receptor inhibitor, used as an antispasmodic drug.Target: nAChRAdiphenine decreased the frequency of ACh-induced single-channel currents. adiphenine decreased cluster duration (36-fold at 100 micromolxL(-1)). adiphenine did not change amplitude but increased the decay rate (IC(50)= 15 micromolxL(-1)) [1]. Adiphenine was administered in3H-labelled form in doses of 15 u.mole/kg intravenously to male Wistar rats. Plasma and brain levels of the unchanged drug were measured [1]. The elimination of the3H -labelled compound from the plasma was monophasic with a half-life of 13 minutes. The unchanged drug was detectable in the plasma for 30 minutes after the injection. The time course of brain levels of unchanged drug paralleled that found in the plasma with a half-life of 9 to 12 minutes. In all experiments, brain and plasma levels of unchanged adiphenine correlate highly [2].
Cyclic ADP-ribose (cADPR) is a potent second messenger for calcium mobilization that is synthesized from NAD+ by a ADP-ribosyl cyclase. Cyclic ADP-ribose increases cytosolic calcium mainly by Ryanodine receptor-mediated release from endoplasmic reticulum and also by extracellular influx through the opening of TRPM2 channels[1].
17β-Estradiol sulfate-d4 (sodium) is the deuterium labeled 17β-Estradiol sulfate 17β-Estradiol sulfate (sodium), also known as β-Estradiol 3-sulfate sodium salt, is a neuroactive steroid[1][2].
Metaflumizone is a semicarbazone insecticide, acts as a potent sodium channel blocker[1].
Nereistoxin (Nereistoxine) is a neurotoxin isolated from the marine annelid Lumbriconereis heteropoda that acts by blocking nicotinic acetylcholine receptors[1].
Tetrabenazine ((+)-) is a reversible inhibitor of vesicular monoamine transporter 2 (VMAT-2), inhibits transport by VMAT2 with 10-fold greater potency than transport by VMAT1. target: VMAT-2In vitro: Tetrabenazine ((+)-) inhibit the activity of the transporter but appear to interact differently with the protein. [2] Tetrabenazine ((+)-) inhibits reserpine binding to the transporter, suggesting that the sites may interact in an allosteric manner. [1]In vivo: 0.9% saline (80%) and dimethylsulfoxide (DMSO) (20%). Tetrabenazine ((+)-) blocks dopamine (DA) storage and depletes striatal DA; Tetrabenazine ((+)-) was shown to induce tremulous jaw movements (TJMs) in rats and mice. The reference dose for administration is 2.0 mg/kg.[2]
NNC-711 (hydrochloride) is a potent and selective inhibitor of GAT-1 ( GABA transporter 1) with an IC50 of 40 nM for hGAT-1. NNC-711 has anticonvulsant and analgesic effect in vivo and exhibits cognition-enhancing activity[1][2][3].
NS11394 is a potent and subtype-selective GABA(A) receptor-positive modulator; possesses a functional efficacy selectivity profile of alpha(5) > alpha(3) > alpha(2) > alpha(1) at GABA(A) alpha subunit-containing receptors.IC50 value:Target: GABA A receptor modulatorin vitro: NS11394 is unique in having superior efficacy at GABA(A)-alpha(3) receptors while maintaining low efficacy at GABA(A)-alpha(1) receptors. NS11394 has an excellent pharmacokinetic profile, which correlates with pharmacodynamic endpoints (CNS receptor occupancy), yielding a high level of confidence in deriving in vivo conclusions anchored to an in vitro selectivity profile and allowing for translation to higher species [2]. in vivo: Oral administration of NS11394 (1-30 mg/kg) to rats attenuated spontaneous nociceptive behaviors in response to hindpaw injection of formalin and capsaicin, effects that were blocked by the benzodiazepine site antagonist flumazenil [1]. NS11394 impairs memory in both rats and mice, which is possibly attributable to its efficacy at GABA(A)-alpha(5) receptors, albeit activity at this receptor might be relevant to its antinociceptive effects [2].
Leptomycin A, a Streptomyces metabolite, is an inhibitor of CRM1 (exportin 1) that blocks CRM1 interaction with nuclear export signals, preventing the nuclear export of a broad range of proteins. Leptomycin A suppresses HIV-1 replication. Less potent than Leptomycin B[1][2].
URAT1 inhibitor 7 (compound 10f) is a potent URAT1 inhibitor, with an IC50 of 12 nM. URAT1 inhibitor 7 exhibits microsomal stability (HLM <13 µL/min/mg). URAT1 inhibitor 7 also inhibits CYP2C9, with an IC50 of 4.2 μM. URAT1 inhibitor 7 can be used for gout research[1].
PPADS tetrasodiuma is a non-selective P2X receptor antagonist. PPADS tetrasodiuma blocks recombinant P2X1, -2, -3, -5 with IC50s ranging from 1 to 2.6 μM. PPADS tetrasodiuma blocks native P2Y2-like (IC50~0.9 mM) and recombinant P2Y4 (IC50~15 mM) receptors. PPADS tetrasodiuma is an inhibitor of the reverse mode of the Na/Ca²⁺exchanger in guinea pig airway smooth muscle[1][2].
Ispronicline (TC-1734), an orally active, brain-selective α4β2 nicotine acetylcholine receptor (nAChR) partial agonist, has shown memory-enhancing properties in rodents and a good tolerability profile. Ispronicline binds to the α4β2 nAChR with high affinity (Ki=11 nM) and is highly selective to other nAChRs such as α7 nAChR and α3β4 nAChR[1][2].
Dibucaine is a local anesthetic of the amide type now generally used for surface anesthesia.Target: Sodium ChannelDibucaine is an amide local anesthetic. Dibucaine reduced the degradation of BSA-gold complex in the reservosomes, which was not caused either by an inhibition of the whole proteolytic activity of the parasite or by a reduction on the expression levels of cruzipain [1].Dibucaine, a quaternary ammonium compound, inhibited SChE to a minimum within 2 min in a reversible manner. The inhibition was very potent. It had an IC(50) of 5.3 microM with BuTch or 3.8 microM with AcTch. The inhibition was competitive with respect to BuTch with a K(i) of 1.3 microM and a linear-mixed type (competitive/noncompetitive) with respect to AcTch with inhibition constants, K(i) and K(I) of 0.66 and 2.5 microM, respectively. Dibucaine possesses a butoxy side chain that is similar to the butryl group of BuTch and longer by an ethylene group from AcTch [2].
L-655708 is a potent α5 subunit-selective GABAA receptor inverse agonist (Ki = 0.45 nM).IC50: 0.45 nM (Ki)Target: GABAin vitro: L-655708 is a potent, selective inverse agonist for the benzodiazepine site of GABAA receptors containing the α5 subunit (Ki = 0.45 nM). Displays 50-100-fold selectivity over GABAA receptors containing α1, α2, α3 orα6 subunits in combination with β3 and γ2. Enhances LTP in a mouse hippocampal slice model and increases spatial learning, without displaying proconvulsant activity.in vivo: L-655708 at 0.7 mg/kg, administered intraperitoneally, would result in 60-70% occupancy of α5 GABAA receptors with limited binding to α1, α2, and α3 subunit-containing GABAA receptors and no significant off-target behavioral effects, such as sedation and motor impairment.[1]
Velagliflozin proline hydrate is the clinical form of Velagliflozin (HY-109018). Velagliflozin is an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor with antidiabetic activity. Velagliflozin reduces renal glucose reabsorption and stimulates glycosuria, which lowers blood sugar and insulin concentrations[1].
AF-353 is a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist, inhibits human and rat P2X3 (pIC50= 8.0).IC50 value: pIC50 = 8.0 (pIC50, for P2X3)Target: P2X3/P2X2/3 receptorin vitro: AF-353 is a highly potent inhibitor of α,β-meATP-evoked intracellular calcium flux in cell lines expressing recombinant rat and human P2X3 and human P2X2/3 channels. AF-353 also blocks human P2X2/3 channel function with marginally reduced potency (pIC50 = 7.3). [1]in vivo: SCI rats has significantly higher frequencies for field potentials and NVC than NL rats. Intravesical ATP increases field potential frequency in control but not SCI rats, while systemic AF-353 significantly reduces this parameter in both groups. AF-353 also reduces the inter-contractile interval in control but not in SCI rats; however, the frequency of NVC in SCI rats was significantly reduced.[2]
Chlorocresol (4-Chloro-3-methylphenol) is a medicine antiseptic.
Levamlodipine besylate ((S)-Amlodipine besylate) is a powerful dihydropyridine calcium channel blocker, possessing vasodilation properties and used in the treatment of hypertension and angina[1].
Calcium channel-modulator-1 is a calcium channel modulator; blocks aortic contraction with an IC50 of 0.8 μM.
BTK inhibitor 4b is a potent, highly selective inhibitors of BTK with IC50 of 4.2 and 0.9 nM against activated and unactivated BTK, respectively; demonstrates significant efficacy in models in vivo and good ADME and safety profiles.
CGP7930 (3-(3’,5’-Di-tert-butyl-4’-hydroxy) phenyl-2, 2-dimethylpropanol) is a positive metabotropic GABAB receptor allosteric modulator. CGP7930 enhances the inhibitory effect of l-baclofen on the oscillatory activity of cultured cortical neurons[1].
Charybdotoxin, a 37-amino acid peptide isolated from venom of the scorpion Leiurus quinquestriatus var. hebraeus, is a K+ channel blocker[1].
Esomeprazole ((S)-Omeprazole) is a potent and orally active proton pump inhibitor and reduces acid secretion through inhibition of the H+, K+-ATPase in gastric parietal cells. Esomeprazole has the potential for symptomatic gastroesophageal reflux disease research[1][2][3].
L-Homocysteic acid (L-HCA) is an endogenous excitatory amino acid that acts as a NMDA receptor agonist (EC50: 14 μM). L-Homocysteic acid is neurotoxic, and can be used in the research of neurological disorders[1][2][3].
U-89843A is an allosteric modulator of GABAA receptor. U-89843A enhances GABA-induced Cl- currents[1].
Leptomycin B (CI 940; LMB) is a potent inhibitor of the nuclear export of proteins. Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue. Leptomycin B is a potent antifungal antibiotic blocking the eukaryotic cell cycle[1].
Nitenpyram is a calss of neonicotinoid and an insect nicotinic acetylcholine receptor (nAChR) agonist with an IC50 of 14 nM. Nitenpyram is an oral fast-acting insecticide used to suppress sucking insects on companion animals[1][2].
L-Glutamic acid-13C2 is the 13C labeled L-Glutamic acid[1]. L-Glutamic acid acts as an excitatory transmitter and an agonist at all subtypes of glutamate receptors (metabotropic, kainate, NMDA, and AMPA). L-Glutamic acid shows a direct activating effect on the release of DA from dopaminergic terminals[2].
α-Conotoxin GIC is a potent and selective α3β2 nicotinic antagonist with an IC50 of 1.1 nM[1].
Neboglamine (CR-2249, XY-2401) hydrochloride is an orally active NMDA receptor glycine site positive modulator that can be used in schizophrenia research[1].