Chloride Channel Inhibitor

Shikonin is a major component of a Chinese herbal medicine named zicao. Shikonin is a potent TMEM16A chloride channel inhibitor with an IC₅₀ of 6.5 μM. Shikonin is a specific pyruvate kinase M2 (PKM2) inhibitor and can also inhibit TNF-α and NF-κB pathway. Shikonin decreases exosome secretion through the inhibition of glycolysis. Shikonin inhibits AIM2 inflammasome activation.

DCPIB is a selective, reversible and potent inhibitor of volume-regulated anion channels (VRAC). DCPIB voltage-dependently activates potassium channels TREK1 and TRAAK, and inhibits TRESK, TASK1 and TASK3 (IC₅₀s: 0.14, 0.95, 50.72 μM, respectively). DCPIB is also a selective blocker of swelling-induced chloride current (I_Cl,swell), with an IC₅₀ of 4.1 μM. DCPIB is a useful tool for investigating structure-function studies of K2P channels.

Flufenamic acid is a non-steroidal anti-inflammatory agent, inhibits cyclooxygenase (COX), activates AMPK, and also modulates ion channels, blocking chloride channels and L-type Ca²⁺ channels, modulating non-selective cation channels (NSC), activating K⁺ channels. Flufenamic acid binds to the central pocket of TEAD2 YBD and inhibits both TEAD function and TEAD-YAP-dependent processes, such as cell migration and proliferation.

Picrotoxinin, a potent convulsant, is a chloride channel blocker. Picrotoxinin is a noncompetitive GABA_A receptor antagonist, which negatively modulates the action of GABA on GABA_A receptors. Picrotoxinin inhibits α₁β₂γ_2L GABA_A receptor with an IC₅₀ of 1.15 μM.

CaCCinh-A01 is an inhibitor of both TMEM16A and calcium-activated chloride channel (CaCC) with IC₅₀s of 2.1 and 10 μM, respectively.

SRA-36 is a CLC-K chloride channel inhibitor with selectivity over CLC-5 and CLC-1 chloride channels. SRA-36 blocks CLC-Ka currents with an IC₅₀ of 6.6 μM and a K_d of 3.8 μM. SRA-36 blocks chloride currents mediated by targeted channels, and inhibits currents from hypertension-associated CLC-Ka^A447T and CLC-Ka^Y315F polymorphisms. SRA-36 can be used for the research of hypertension.

Ani9 is an ANO1 inhibitor, with an IC₅₀ of 77 nM. Ani9 can inhibit smooth muscle contractions in mice and is applicable in research related to diseases such as tumors.

R(+)-Methylindazone (R(+)-IAA-94) is a potent indanyloxyacetic acid blocker of epithelial chloride channels. R(+)-Methylindazone inhibits Nef-sdAb19 (single-domain antibody) interaction and binds to negative factor (Nef).

T16Ainh-A01, an aminophenylthiazole, is a potent transmembrane protein 16A (TMEM16A) inhibitor, inhibiting TMEM16A-mediated chloride currents with an IC₅₀ value of ~1 µM. TMEM16A (ANO1) functions as a calcium-activated chloride channel (CaCC).

Niflumic acid is a calcium-activated chloride channel blocker and COX-2 inhibitor with the IC₅₀ value of 100 nM. Niflumic acid induces apoptosis through caspase-8/Bid/Bax pathway in lung cancer cells. Niflumic acide exhibits anti-tumor activity by affecting the expression of ERK1/2 and the activity of MMP2 and MMP9. Niflumic acid has orally bioactivity. Niflumic acid acts on rheumatoid arthritis.

NPPB is a blocker of the outwardly rectifying chloride channel (ORCC).

Afoxolaner is an orally active isoxazoline insecticide/acaricide against Ixodes scapularis in dogs. Afoxolaner acts on the insect γ-aminobutyric acid receptor (GABA) and glutamate receptors, inhibiting GABA & glutamate-regulated uptake of chloride ions, resulting in excess neuronal stimulation and death of the arthropod.

ANO1-IN-1 (Compound 9c) is a selective ANO1 channel blocker with an IC₅₀ of 2.56 μM and 15.43 μM against ANO1 and ANO2, respectively. ANO1-IN-1 suppresses strongly proliferation of glioblastoma cells.

Steviol is the main metabolite of steviol glycosides and an inhibitor of AQP2/CFTR. Steviol slows down the growth of renal cysts by inhibiting the activity of CFTR, reducing the expression of AQP2, and promoting the degradation of AQP2 and CFTR. Steviol can be used in the research of polycystic kidney disease.

S9-A13 is a potent and selective inhibitor SLC26A9, with the IC₅₀ of 90.9 nM, without inhibiting other members of the SLC26 family such as SLC26A3, SLC26A4, and SLC26A6. S9-A13 can inhibits SLC26A9 Cl^- currents in cells that lack expression of CFTR.

PAT1inh-B01 is a selective SLC26A6 inhibitor. PAT1inh-B01 inhibits PAT1 (a Cl^-/HCO3^- exchanger)-mediated anion exchange (IC₅₀: 350 nM). PAT1inh-B01 blocks fluid absorption in small intestine. PAT1inh-B01 can be used for research of small intestinal hyposecretory disorders.

Anthracene-9-carboxylic acid (9-Anthracenecarboxylic acid) is an anthracene derivative traditionally used to block and identify Ca²⁺-activated Cl^- currents (CaCCs) in various cell types, like diverse smooth muscle cells, epithelial cells and salivary gland cells.

Endovion is a pharmacological anion channel inhibitor (like chloride channel) and the specific VRAC/VSOAC blocker. Endovion (NS3728) is also an Anoctamin-1 (ANO 1) channel inhibitor.

NMD670 is an orally active inhibitor of skeletal muscle specific chloride channel ClC-1 with an EC₅₀ of 1.6 μM. NMD670 enhances neuromuscular transmission and improves muscle contraction and strength. NMD670 can be used in the study of muscle weakness and muscle fatigue.

Chlorotoxin is a 36 amino-acid peptide from the venom of the Israeli scorpion Leiurus quinquestriatus with anticancer activity. Chlorotoxin is a chloride channel blocker.