Chloride Channel
Chloride (Cl ) is the most abundant ion in nature. It is transported by several distinct families of chloride transporting proteins including chloride channels (ClC), ligand gated GABA and glycine receptors, cystic fibrosis conductance transmembrane regulators, cation chloride transporters, and chloride/bicarbonate exchangers. To date, there are nine known members of the human ClC family. All ClC proteins have a transmembrane catalytic domain and most (all eukaryotic types and a few prokaryotic types) have a cytoplasmic regulatory domain. These are categorized into three groups based on their sequence homology. The first group comprises the Cl channels: ClC-1, ClC-2, and the kidney-specific chloride channels ClC-Ka and ClC-Kb. The remaining proteins, classified as group 2 and 3, are electrogenic Cl /Hþ antiporters, whose distribution and physiological functions are distinct from the Cl channel proteins.
These five proteins (ClC-3, ClC-4, and ClC-5 in group 2; and ClC-6 and ClC-7 in group 3) are predominantly found in intravascular membranes of the endosomal-lysosomal pathway and are only expressed to a limited extent at the plasma membrane. The two best-characterized Cl /Hþ antiporters so far are ClC-5 and ClC-7. The group 3 antiporter proteins, ClC-6 and ClC-7, are thought to facilitate protein degradation by regulating Cl ion concentration to ensure optimal function of the hydrolytic enzymes of late endosomes and lysosomal compartments. Evidence of a role for ClC proteins in human disease comes from genetic studies linking mutations in these proteins to the occurrence of many hereditary diseases. Clarification of these processes requires a thorough understanding of the behavior of ClC proteins at the molecular level.
References
1.Abeyrathne PD,et al. Biochimie. 2016 Sep-Oct;128-129:154-62.
These five proteins (ClC-3, ClC-4, and ClC-5 in group 2; and ClC-6 and ClC-7 in group 3) are predominantly found in intravascular membranes of the endosomal-lysosomal pathway and are only expressed to a limited extent at the plasma membrane. The two best-characterized Cl /Hþ antiporters so far are ClC-5 and ClC-7. The group 3 antiporter proteins, ClC-6 and ClC-7, are thought to facilitate protein degradation by regulating Cl ion concentration to ensure optimal function of the hydrolytic enzymes of late endosomes and lysosomal compartments. Evidence of a role for ClC proteins in human disease comes from genetic studies linking mutations in these proteins to the occurrence of many hereditary diseases. Clarification of these processes requires a thorough understanding of the behavior of ClC proteins at the molecular level.
References
1.Abeyrathne PD,et al. Biochimie. 2016 Sep-Oct;128-129:154-62.
Membrane Transporter/Ion Channel
AMPK(58)
ASBT Transporter(6)
BCRP(10)
Beta Amyloid(69)
Carbonic Anhydrase(40)
Chloride Channel(34)
CRAC Channel(0)
CRM1(5)
Exportin-1(5)
FABP(6)
GAT(63)
GLUT(5)
Glutamate Transporter(1)
GlyT(13)
HCN Channel(5)
iGluR(52)
Monoamine Transporter(26)
Monocarboxylate Transporter(12)
MTP(1)
nAChR(5)
NADPH(35)
Na-K-ATPase(2)
NKCC(4)
NMDAR(65)
OCT(4)
Other Targets(13)
P2X Receptor(23)
P-glycoprotein(14)
Proton Pump(38)
Sodium Channel(147)
TRP/TRPV Channel(115)
URAT1(1)
Chloride Channel
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ANO1-IN-1
catalog no : M35506
cas no: 407587-01-3
ANO1-IN-1, a selective ANO1 channel blocker, inhibited ANO1 and ANO2 with IC50 values of 2.56 μM and 15.43 μM, respectively.ANO1-IN-1 had a significant inhibitory effect on the proliferation of glioma cells. -
GaTx2
catalog no : M30682
cas no: 194665-85-5
Very high affinity ClC-2 blocker (apparent KD ~ 50 pM). Slows ClC-2 activation and inhibits slow-gating but does not inhibit open ClC-2 channels. Selective for ClC-2 over other ClC family members (ClC-0, ClC-1, ClC-3 and ClC-4), CFTR, GABAC, CaCC and KV1.2. -
Org 25543
catalog no : M28443
cas no: 363628-88-0
Org 25543 is the development of an N-Acyl amino acid that selectively inhibits the glycine transporter 2 to produce analgesia in a rat model of chronic pain. -
Ani9
catalog no : M27849
cas no: 356102-14-2
Ani9 is a high selective blocker of Anoctamin1 (ANO1)/transmembrane protein 16A (TMEM16A) with an IC50 of 77 nM and can be used in studies about ANO1 and the treatment of ancer, hypertension, pain, diarrhea and asthma. -
Fenamic acid
catalog no : M27555
cas no: 91-40-7
Fenamic acid is a chloride channel blocker that causes renal papillary necrosis in rats. Fenamic acid serves as a parent structure for several nonsteroidal anti-inflammatory drugs (NSAIDs), including flufenamic acid, tolfenamic acid, mefenamic acid, and meclofenamic acid.