(Rac)-AMG8379 ((Rac)-AMG8380) is a racemate of AMG8379. AMG8379 is a potent, orally active and selective sulfonamide antagonist of NaV1.7, with IC50s of 8.5 and 18.6 nM for hNaV1.7 and mNaV1.7, respectively [1].
N-Methyl duloxetine-d7 is the deuterium labeled N-Methyl Duloxetine. N-Methyl Duloxetine is an analgesic. N-Methyl Duloxetine elicits both tonic and use-dependent block of neuronal Na+ channels[1][2].
Topiramate D12 (McN 4853 D12) is a deuterium labeled Topiramate. Topiramate is a broad-spectrum antiepileptic agent. Topiramate is a GluR5 receptor antagonist. Topiramate produces its antiepileptic effects through enhancement of GABAergic activity, inhibition of kainate/AMPA receptors, inhibition of voltage-sensitive sodium and calcium channels, increases in potassium conductance, and inhibition of carbonic anhydrase[1][2][3].
4-Chlorophenylguanidine hydrochloride is a potent ASIC3 positive allosteric modulator and reverses the effects of ASIC3 desensitization. 4-Chlorophenylguanidine hydrochloride influences ASIC3 activity through directly activating the channel and increasing proton sensitivity. 4-Chlorophenylguanidine hydrochloride offers a chemical backbone for the design of new ASIC3 ligands to study ASIC3 in vivo[1].
Phenamil methanesulfonate, an analog of Amiloride (HY-B0285), is a more potent and less reversible epithelial sodium channel (ENaC) blocker with an IC50 of 400 nM[2]. Phenamil methanesulfonate is also a competive inhibitor of TRPP3 and inhibits TRPP3-mediated Ca2+ transport with an IC50 of 140 nM in a Ca2+ uptake assay[1]. Phenamil methanesulfonate is an intriguing small molecule to promote bone repair by strongly activating BMP signaling pathway[4]. Phenamil methanesulfonate is used for the research of cystic fibrosis lung disease[5].
μ-Conotoxin SIIIA is a tetrodotoxin (TTX)-resistant sodium channel blocker. μ-Conotoxin SIIIA is a toxic peptide that can be obtained from the venom of Conus snails. μ-Conotoxin SIIIA can be used in the study of neurological diseases, such as neuropathic pain[1].
GpTx-1 is a potent, selective, 34-residue peptide antagonist of Nav1.7 sodium channel with IC50 of 10 nM, displays 20- and 1000- fold selectivity over NaV1.4 and NaV1.5.
Propafenone-(phenyl-dd5) (hydrochloride) is the deuterium labeled Propafenone hydrochloride[1]. Propafenone hydrochloride is a class of anti-arrhythmic medication, which treats illnesses associated with rapid heart beats such as atrial and ventricular arrhythmias[2].
Amiloride (hydrochloride) is an epithelial sodium channel (ENaC) inhibitor and a competitive inhibitor of Urokinase-type plasminogen activator (uPA).
Dibucaine Hydrochloride 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].
NaV1.7 inhibitor-1 is an efficacious voltage-gated sodium channel (NaV) 1.7 inhibitor with an IC50 of 0.6 nM for hNaV1.7, exhibits 80-fold selectivity versus hNaV1.5[1].
Zoniporide (CP-597396) hydrochloride hydrate is a potent and selective inhibitor of sodium-hydrogen exchanger type 1 (NHE-1). Zoniporide hydrochloride hydrate inhibits human NHE-1 (IC50=14 nM), and has >150-fold selectivity versus other NHE isoforms. Zoniporide hydrochloride hydrate potently inhibits ex vivo NHE-1-dependent swelling of human platelets (IC50=59 nM)[1][2].
Hainantoxin-IV is a specific antagonist of Sodium Channel, targeting to tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channels. His28 and Lys32 are the key resiudes of Hainantoxin-IV for binding with target, while Hainantoxin-IV adopts an inhibitor cystine knot motif[1].
Amitriptyline Hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA).Target: OthersAmitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter and moderate effects on the norepinephrine transporter. It has negligible influence on the dopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than on serotonin [1]. Amitriptyline additionally functions as a 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, H1, H2, and mACh receptorantagonist, and σ1 receptor agonist. It has also been shown to be a relatively weak NMDA receptor negative allosteric modulator at the same binding site as phencyclidine. Amitriptyline inhibits sodium channels, L-type calcium channels, and Kv1.1, Kv7.2, and Kv7.3 voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well [2]. Recently, amitriptyline has been demonstrated to act as an agonist of the TrkA and TrkB receptors. It promotes the heterodimerization of these proteins in the absence of NGF and has potent neurotrophic activity both in-vivo and in-vitro in mouse models [3].
Lidocaine Hcl salt, an amide local anesthetic, has anti-inflammatory properties in vitro and in vivo, possibly due to an attenuation of pro-inflammatory cytokines, intracellular adhesion molecule-1 (ICAM-1), and reduction of neutrophils influx.Target: Lidocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery. Lidocaine, the first amino amide–type local anesthetic, was first synthesized under the name xylocaine by Swedish chemist Nils Lofgren in 1943. His colleague Bengt Lundqvist performed the first injection anesthesia experiments on himself.Lidocaine is approximately 95% metabolized (dealkylated) in the liver by CYP3A4 to the pharmacologically-active metabolites monoethylglycinexylidide (MEGX) and then subsequently to the inactive glycine xylidide. MEGX has a longer half life than lidocaine but also is a less potent sodium channel blocker. The elimination half-life of lidocaine is approximately 90–120 minutes in most patients. This may be prolonged in patients with hepatic impairment (average 343 minutes) or congestive heart failure (average 136 minutes).
Sodium Channel inhibitor 2 is a sodium channel blocker extracted from patent WO 2004011439 A2, compound 3c.
Mepivacaine is a tertiary amine used as a local anesthetic.Target: Sodium ChannelMepivacaine is a local anesthetic of the amide type. Mepivacaine has a reasonably rapid onset (more rapid than that of procaine) and medium duration of action (shorter than that of procaine). Mepivacaine is used in any infiltration and regional anesthesia. It is supplied as the hydrochloride salt of the racemate [1]. Mepivacaine displayed a preferential use-dependent block of Na(v)1.8, S(-)-bupivacaine displayed a preference for TTXs Na(+) channels [2].
Budiodarone (ATI-2042) tartrate is a chemical analogue of Amiodarone (HY-14187) with balanced, multiple cardiac ion channel (potassium, sodium and calcium channels) inhibiting activity. Budiodarone tartrate is an antiarrhythmic agent[1].
Irampanel (BIIR 561) is an AMPA receptor and voltage-dependent sodium channel blocker. Irampanel inhibits kainate-induced currents in rat cortical neurons[1].
GDC-0310 is a selective acyl-sulfonamide Nav1.7 inhibitor, with an IC50 of 0.6 nM for hNav1.7[1].
Brevetoxin B (Brevetoxin-2; PbTx-2) is a polyketide neurotoxin produced by Karenia species and other dinoflagellates. Brevetoxin B binds to site 5 on the alpha subunit of voltage-gated sodium channels (IC50=15 nM) on neurons at the neuromuscular junction, causing the channel to open irreversibly at potentials more negative than normal, discharging action potentials repetitively. Brevetoxin B is ichthyotoxic at nanomolar concentrations and is responsible for an illness described as neurotoxic shellfish poisoning.
YM758 is a “funny” If current channel (If channel) inhibitor.
Bliretrigine is a sodium channel blocker. Bliretrigine has the effect of relieving pain[1][2][3].
Mepivacaine is an amide-type local anesthetic agent. Mepivacaine binds to specific voltage-gated sodium ion channels in neuronal cell membranes, which inhibits both sodium influx and membrane depolarization[1][2].
NHE3-IN-1 is a sodium/proton exchanger type 3 (NHE-3) inhibitor extracted from patent WO 2011019784 A1.
Nav1.7-IN-3 is a selective, orally bioavailable voltage-gated sodium channel Nav1.7 inhibitor with an IC50 of 8 nM. Pain relief. Limited CNS penetration[1].
μ-Conotoxin KIIIA is an analgesic μ-conotoxin that can be isolated from Conus kinoshitai. μ-Conotoxin KIIIA blocks mammalian neuronal voltage-gated sodium channels (VGSCs) (Nav1.2).μ-Conotoxin KIIIA can be used for research of pain[1][2].
SLC13A5-IN-1 is a selective sodium-citrate co-transporter (SLC13A5) inhibitor. SLC13A5-IN-1 completely blocks the uptake of 14C-citrate with an IC50 value of 0.022 μM in HepG2 cells. SLC13A5-IN-1 has the potential for the treatment of metabolic and/or cardiovascular diseases. SLC13A5-IN-1 is extracted from patent WO2018104220A1, Compound I-5[1].
Zoniporide (CP-597396) hydrochloride is a potent and selective inhibitor of sodium-hydrogen exchanger type 1 (NHE-1). Zoniporide hydrochloride inhibits human NHE-1 (IC50=14 nM), and has >150-fold selectivity versus other NHE isoforms. Zoniporide hydrochloride potently inhibits ex vivo NHE-1-dependent swelling of human platelets (IC50=59 nM)[1][2].