AZD-5672 is an orally active, potent, and selective CCR5 antagonist (IC50=0.32 nM). AZD-5672 shows moderate activity against the hERG ion channel (binding IC50=7.3 μM). AZD5672 is a substrate of human P-gp, and inhibits P-gp-mediated digoxin transport (IC50=32 μM). AZD-5672 can be used for the research of rheumatoid arthritis[1][2][3].
Posenacaftor (PTI-801) is a cystic fibrosis transmembrane regulator (CFTR) protein modulator that corrects the folding and trafficking of CFTR protein. Posenacaftor is used for the research of cystic fibrosis (CF)[1].
LY2365109 is a potent and selective GlyT1 inhibitors with IC50 value of 15.8 nM.target: GlyT1[1]IC 50: 15.8 nM [1]In vivo: The reference for LY2365109 is 0.3 or 30 mg/kg by PO. LY2365109 appeared slightly more potent than ALX5407 over the dose-range tested on CSF levels of glycine in the ratLY2365109 can act to potentiate NMDA function in the PFC but also mediate sustained inhibition of GlyT1 transporters in caudal areas of the brain.[1] LY2365109 increased seizure thresholds in mice. Importantly, chronic seizures in the mouse model of TLE were robustly suppressed by systemic administration of the GlyT1 inhibitor LY2365109. [2]
Tiagabine hydrochloride hydrate is a potent and selective GABA uptake inhibitor, used as an anticonvulsant agent, with IC50s of 67, 446 and 182 nM for [3H]GABA uptake in Synaptosomes, Neurons and Glia, respectively[1].
Glycine is an inhibitory neurotransmitter in the CNS and also acts as a co-agonist along with glutamate, facilitating an excitatory potential at the glutaminergic N-methyl-D-aspartic acid (NMDA) receptors.
PNU-282987 is a selective α7 nicotinic acetylcholine receptor(α7 nAChR) agonist with Ki of 26 nM; no affinity for α1β1γδ and α3β4 nAChRs (IC50 ≥ 60 μM).IC50 value: 26 nM(Ki) [1]Target: α7 nAChR agonistin vitro: Treatment with PNU-282987 resulted in an attenuation of neuroinflammation in the MPTP-lesioned SN. Furthermore, PNU-282987 attenuated MPTP-induced dopaminergic cell loss in the SN and reduced striatal dopamine depletion [3].in vivo: Mice were subjected to 70% partial hepatic I/R for 60 min and pretreated with either vehicle or with PNU-282987, and blood and hepatic tissue samples were collected at 3, 6, and 12 h following reperfusion. pretreatment with PNU-282987 decreased serum transaminase levels and ameliorated liver injury after hepatic I/R. Moreover, pretreatment with PNU-282987 suppressed NF-κB activation, cytokine production (tumor necrosis factor α, interleukin 1β), and HMGB1 expression in liver after hepatic I/R [2]. Mice treated with 2.5 and 10 mg/kg of PNU devoted less time to rearing into open arms. In the HB task, MC mice displayed higher exploratory activity reflected in more head-dips (HD) during the first minute than EE and SE, whereas EE displayed low exploration levels reflected in total HD (5 min) [4].
GSK1016790A is a potent transient receptor potential vanilloid 4 (TRPV4) activator.
ILS-920 is a nonimmunosuppressive Rapamycin analog with reduced immunosuppressive activity and potent neuroprotective activity. ILS-920 binds selectively to the immunophilin FKBP52 and to the β1-subunit of L-type voltage-gated calcium channels (VGCC). ILS-920 shows 200-fold selectivity for FKBP52 versus FKBP12[1].
Dihydroisopimaric acid activates large conductance Ca2+ activated K+ (BK) channels alphabeta1 in the direct measurement of BKalphabeta1 opening under whole-cell voltage clamp[1].
Halazone is an atypical antimicrobial sulfonamide derivative and a carbonic anhydrase II inhibitor with a Kd value of 1.45 µM. Halazone protects sodium channels from inactivation. Halazone is widely used for disinfection of drinking water[1][2].
Ginkgolide A is an extract from in Ginkgo biloba and a g-aminobutyric acid (GABA) antagonist.Target: GABA ReceptorGinkgolide A is a highly active PAF antagonist cage molecule that is isolated from the leaves of the Ginkgo biloba tree. Shows potential in a wide variety of inflammatory and immunological disorders. Ginkgolide A significantly shortened the sleeping time induced by anesthetics in mice [1]. Ginkgolide A failed to affect apoptotic damage neither in serum-deprived nor in staurosporine-treated neurons [2].
Ro 25-6981 Maleate is a potent and selective activity-dependent blocker of NMDA receptors containing the NR2B subunit. IC50 values are 0.009 and 52 μM for cloned receptor subunit combinations NR1C/NR2B and NR1C/NR2A respectively.IC50 value: 9 nM [1]Target: NMDA receptor subtype of NR1C & NR2Bin vitro: Ro 25-6981 inhibited 3H-MK-801 binding to rat forebrain membranes in a biphasic manner with IC50 values of 0.003 microM and 149 microM for high- (about 60%) and low-affinity sites, respectively. NMDA receptor subtypes expressed in Xenopus oocytes were blocked with IC50 values of 0.009 microM and 52 microM for the subunit combinations NR1C & NR2B and NR1C & NR2A, respectively, which indicated a >5000-fold selectivity [1]. Increasing the concentration of spermidine did not change the efficacy of RO 25-6981 and minimally changed the IC(50) value. Epsilon1Q336R receptors were more inhibited by ifenprodil and RO 25-9681 than wildtype epsilon1 receptors in ligand binding assays but not in functional assays [2].in vivo: Intrathecal injection of Ro 25-6981 significantly enhanced the paw withdrawal mechanical threshold and paw withdrawal thermal latency after the operation. Significant change has been observed after intrathecal injection of 800.0 μg of Ro 25-6981 and at 2h after operation in the oblique pull test degree and BBB rating score. Pretreatment of Ro 25-6981 decreased the high level expression of NR2B with tyrosine phosphorylation in spinal dorsal horn of the rat model after the operation [3].
Hydroxyisobakuchiol (Delta3,2-Hydroxylbakuchiol), an analog of Bakuchiol (HY-N0235) isolated from Psoralea corylifolia (L.), is a potent monoamine transporter inhibitor. 13-Hydroxyisobakuchiol is more selective for the dopamine transporter (DAT) (IC50=0.58 μM) and norepinephrine transporter (NET) (IC50=0.69 μM) than for the serotonin transporter (SERT) (IC50=312.02 μM). 13-Hydroxyisobakuchiol has the potential for the research of disorders such as Parkinson's disease, depression, and cocaine addiction[1].
Omeprazole D3 is deuterium labeled Omeprazole, which is a proton pump inhibitor used in the treatment of dyspepsia.
KCNQ2/3 activator-1 is an activator of Kv7.2/Kv7.3 (KCNQ2/3) potassium channel. KCNQ2/3 activator-1 has the potential in relieving pain (the main problem from medical treatment) (extracted from patent WO2021113757A1, compound A)[1].
DPNI-GABA is a nitroindoline cage compound that inhibits GABA(A) receptors and reduces GABA-evoked peak responses with an IC50 value of 0.5 mM[1].
Pilsicainide hydrochloride (SUN-1165) is an orally active sodium channel blocker and potent class Ic antiarrhythmic agent[1][2].
Dirocaftor (PTI-808) is a CFTR potentiator that enhances the function of CFTR protein by opening chloride channels. Dirocaftor can be used for cystic fibrosis (CF) research[1][2].
Tigolaner is a GABA antagonist that regulates chloride channel. Tigolaner is an antiparasitic agent[1].
(-)-Sparteine (sulfate) is a quinolizidine alkaloid that can be extracted from Lupinus. (-)-Sparteine (sulfate) inhibits the release of acetylcholine and has anticonvulsant effects[1].
Azimilide 2Hcl(NE-10064 2Hcl) is a class III antiarrhythmic compound, inhibits I(Ks) and I(Kr) in guinea-pig cardiac myocytes and I(Ks) (minK) channels expressed in Xenopus oocytes.IC50 value:Target: in vitro: Azimilide blocked HERG channels at 0.1 and 1 Hz with IC50s of 1.4 microM and 5.2 microM respectively. Azimilide blockade of HERG channels expressed in Xenopus oocytes and I(Kr) in mouse AT-1 cells was decreased under conditions of high [K+]e, whereas block of slowly activating I(Ks) channels was not affected by changes in [K+]e [1]. Azimilide suppressed the following currents (Kd in parenthesis): IKr (< 1 microM at -20 mV), IKs (1.8 microM at +30 mV), L-type Ca current (17.8 microM at +10 mV), and Na current (19 microM at -40 mV). Azimilide was a weak blocker of the transient outward and inward rectifier currents (Kd > or = 50 microM at +50 and -140 mV, respectively). Azimilide blocked IKr, IKs, and INa in a use-dependent manner. Furthermore, azimilide reduced a slowly inactivating component of Na current that might be important for maintaining the action potential plateau in canine ventricular myocytes [2]. In guinea pig ventricular myocytes, NE-10064 (0.3-3 microM) significantly prolonged action potential duration (APD) at 1 Hz. At 3 Hz, NE-10064 (0.3-1 microM) increased APD only slightly, and at 10 microM decreased APD and the plateau potential. NE-10064 potently blocked the rapidly activating component of the delayed rectifier, IKr (IC50 0.4 microM), and inhibited IKs (IC50 3 microM) with nearly 10-fold less potency [3].in vivo: NE-10064 (10 mg/kg intravenously, i.v.) reduced (p < 0.05) the incidence (8 of 12) of PES-induced ventricular tachycardia (VT). The cycle length of induced VT was not prolonged by NE-10064 (0.245 +/- 0.046 s predrug vs. 0.301 +/- 0.060 s postdrug). NE-10064 increased ventricular effective refractory period (VERP 166 +/- 5 ms predrug vs. 194 +/- 13 ms postdrug, p = 0.013), prolonged QTc interval (310 +/- 12 ms predrug vs. 350 +/- 16 ms postdrug, p = 0.004) and prolonged the effective refractory period (ERP) of noninfarcted myocardium (p = 0.045) [4].
CIQ is a subunit-selective potentiator of NMDA receptors containing the NR2C or NR2D subunit. IC50 value: 2.7 μM (EC50, for NR2C) and 2.8 μM (EC50, NR2D)Target: NMDA receptorCIQ increases channel opening frequency of recombinant NR2Cor NR2D containing receptors by two-fold (EC50 = 2.7 and 2.8 μM, respectively), with no effect on NR2A or NR2B subtypes. CIQ does not alter the EC50 values for glutamate or glycine on channel opening. CIQ increases channel opening efficiency and enhances NMDA receptor responses. CIQ reduces associated behaviours in schizophrenia models and potentially enhances dopamine release in Parkinson's disease models.
α-Conotoxin GI has high affinity for nAChR.α-Conotoxin GI is a short peptide toxin that can be isolated from the venom of Conus geographus.α-Conotoxin GI has the similar activity with neuromuscular blocking agent[1][2][3].
Phenytoin-15N2,13C is the 13C and 15N labeled Phenytoin[1]. Phenytoin (5,5-Diphenylhydantoin) is a potent Voltage-gated Na+ channels (VGSCs) blocker. Phenytoin has antiepileptic activity and reduces breast tumour growth and metastasis in mice[2][3].
(R)-Lercanidipine hydrochloride is the R-enantiomer of Lercanidipine. (R)-lercanidipine hydrochloride is a calcium channel blocker[1].
Etripamil (MSP-2017) is a short-acting L-type calcium-channel antagonist with a rapid onset of action designed for intranasal administration, used to treat Paroxysmal Supraventricular Tachycardia (PSVT). Etripamil (MSP-2017) slows atrioventricular nodal conduction and prolongs atrioventricular nodal refractory periods by inhibiting calcium ion influx through the calcium slow channels in the atrioventricular node cells[1][2].
μ-Conotoxin GIIIB is a 22-residue polypeptide that can be isolated from the venom of piscivorous cone snail Conus geographus. μ-Conotoxin GIIIB is a NaV1.4 channel inhibitor. μ-Conotoxin GIIIB blocks muscle cell's contraction[1][2][3].
Ro 8-4304 hydrochloride is a potent NMDA receptor antagonist. Ro 8-4304 hydrochloride is a NR2B selective, non-competitive, voltage-independent antagonist[1].
Henagliflozin (SHR3824) is a potent selective sodium-glucose co-transporter 2 (SGLT2) inhibitor with the IC50 values of 2.38 and 4324 nM for human SGLT2 and SGLT1, respectively. Henagliflozin can be used in diabetes research[1].
Xininurad (XNW3009) is a urate transporter (URAT) inhibitor[1]