Calcium Channel Inhibitor

L-Ascorbic acid (L-Ascorbate), an electron donor, is an endogenous antioxidant agent. L-Ascorbic acid inhibits selectively Ca_v3.2 channels with an IC₅₀ of 6.5 μM. L-Ascorbic acid is also a collagen deposition enhancer and an elastogenesis inhibitor. L-Ascorbic acid exhibits anti-cancer effects through the generation of reactive oxygen species (ROS) and selective damage to cancer cells.

Thapsigargin, an endoplasmic reticulum (ER) stress inducer, is an inhibitor of microsomal Ca²⁺-ATPase. Thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types.

2-Aminoethyl diphenylborinate (2-APB) is a cell-permeable inhibitor of Inositol triphosphate receptor (IP3R). 2-Aminoethyl diphenylborinate also inhibits the store-operated Ca²⁺ (SOC) channel and activates some TRP channels (V1, V2 and V3). Additionally, 2-Aminoethyl diphenylborinate has inhibitory effects on vasospasm. At high concentrations, it exhibits specific anti-inflammatory and antioxidant effects in neural tissue.

Cerebellin TFA is a neuromodulatory hexadecapeptide that serves as a marker for Purkinje cell maturation. Cerebellin TFA stimulates norepinephrine release via the adenylate cyclase/PKA-dependent signaling pathway. Cerebellin TFA reduces insulin secretion from pancreatic islets under high-glucose conditions. Cerebellin TFA also regulates synaptic structure formation and controls catecholamine secretion in peripheral tissues. Cerebellin TFA can be used in neurological research.

L-Ascorbic acid sodium salt (Sodium ascorbate), an electron donor, is an endogenous antioxidant agent. L-Ascorbic acid sodium salt selectively inhibits Ca_v3.2 channels with an IC₅₀ of 6.5 μM. L-Ascorbic acid sodium salt is also a collagen deposition enhancer and an elastogenesis inhibitor.

Ebselen (SPI-1005), a glutathione peroxidase mimetic, is a potent voltage-dependent calcium channel (VDCC) blocker. Ebselen potently inhibits M^pro (IC₅₀=0.67 μM) and COVID-19 virus (EC₅₀=4.67 μM).Ebselen is an inhibitor of HIV-1 capsid CTD dimerization. Ebselen, an organoselenium compound, can permeate the blood-brain barrier and has anti-inflammatory, antioxidant and anticancer activity.

Gabapentin is a potent, orally active P/Q type Ca²⁺ channel blocker. Gabapentin inhibits neuronal Ca²⁺ influx and reduction of neurotransmitter release. Gabapentin is a GABA analog that can be used to relieve neuropathic pain.

Halofuginone (RU-19110), a Febrifugine derivative, is a competitive prolyl-tRNA synthetase inhibitor with a K_i of 18.3 nM. Halofuginone is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-β activity. Halofuginone is also a potent pulmonary vasodilator by activating Kv channels and blocking voltage-gated, receptor-operated and store-operated Ca²⁺ channels. Halofuginone has anti-malaria, anti-inflammatory, anti-cancer, anti-fibrosis effects.

Carbamazepine is an orally active pressure-sensitive sodium ion channel blocker with an IC₅₀ of 131 μM. Carbamazepine blocks voltage gated Na⁺, Ca²⁺, and K⁺ channels, and is also a HDAC inhibitor (IC₅₀: 2 μM). Carbamazepine is an anticonvulsant and can be used for research of epilepsy and neuropathic pain.

Ruthenium red (Ammoniated ruthenium oxychloride) is a polycationic dye widely used for electron microscopy (EM) of cells, tissues and vegetative bacteria. Ruthenium red strongly reacts with phospholipids and fatty acids and binds to acidic mucopolysaccharides. Ruthenium red is a L-type calcium current (I_Ca) blocker.

Tetrandrine (NSC-77037; d-Tetrandrine) is a bis-benzyl-isoquinoline alkaloid, which inhibits voltage-gated Ca²⁺ current (ICa) and Ca²⁺-activated K⁺ current.

Spironolactone is an aldosterone antagonist that acts on the aldosterone mineralocorticoid receptor (IC₅₀=24 nM) and androgen receptor (IC₅₀=77 nM), promotes podocyte autophagy and regulates pain. Spironolactone improves hypertension-related vascular hypertrophy and remodeling by reducing angiotensin II (Ang II)-induced inflammation, reduces aldosterone-induced vascular and soft tissue calcification through PIT1-dependent signaling, and alleviates vascular dysfunction in type II diabetic mice by reducing oxidative stress and restoring NO/GC signaling; at low concentrations, it and its metabolites can interfere with aldosterone biosynthesis in the adrenal cortex and inhibit voltage-dependent Ca²⁺ channels to exert antihypertensive effects.

Nimodipine (BAY-e 9736) is an orally active, well-tolerated and light-sensitive dihydropyridine calcium antagonist. Nimodipine can be used for the research of cerebrovascular disorders.

8-Bromo-cGMP sodium, a membrane-permeable analogue of cGMP, is a PKG (protein kinase G) activator. 8-Bromo-cGMP sodium significantly inhibits Ca²⁺ macroscopic currents and impairs insulin release stimulated with high K⁺. 8-Bromo-cGMP sodium has antinociceptive effects and results in vasodilator responses.

Dantrolene is an orally active, non-competitive glutathione reductase inhibitor with a K_i of 111.6 μM and an IC₅₀ of 52.3 μM. Dantrolene is also a calcium channel protein inhibitor. Dantrolene inhibits the release of Ca²⁺ from RyR1 and RyR3, which can be beneficial in a variety of pathologies caused by disruptions in calcium homeostasis (e.g., stroke, ischemia/reperfusion injury, and neurodegenerative diseases). Dantrolene offers relief of muscle spasms, malignant hyperthermia, and antitoxic, antipyretic, and anti-inflammatory properties.

Xestospongin C ((-)-Xestospongin C) is a selective, reversible inositol 1,4,5-trisphosphate receptor (IP3R) inhibitor. Xestospongin C acts as an inhibitor of the sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase (SERCA) pump of internal stores. Xestospongin C blocks IP3-induced Ca²⁺ release from cerebellar microsomes with an IC₅₀ of 358 nM. Xestospongin C is a valuable tool for investigating the structure and function of IP3Rs and Ca²⁺ signaling in neuronal and nonneuronal cells.

Ethacrynic acid has anti-inflammatory and anticancer activity. Ethacrynic acid is an orally active diuretic. Ethacrynic acid is an inhibitor of glutathione S-transferase (GSTs) and Wnt signaling pathways. Ethacrynic acid is a radiosensitizer. Ethacrynic acid can inhibit airway smooth muscle (ASM) contraction in mice. Ethacrynic acid can increase the outflow of aqueous humor from the eye for the study of glaucoma.

SKF-96365 hydrochloride is a TRPC channel antagonist and store-operated calcium entry (SOCE) inhibitor. SKF-96365 hydrochloride reduces calcium ion influx by inhibiting the activity and expression of TRPC6, STIM1 and Orai1. SKF-96365 hydrochloride inhibits voltage-gated sodium current (cardiac I_Na/NaV1.5) and slows myocardial conduction. SKF-96365 hydrochloride inhibits phosphorylation/activation of CaMKIIγ and suppresses the downstream AKT signaling pathway. SKF-96365 hydrochloride induces G₂/M phase cell cycle arrest, apoptosis and cytoprotective autophagy in colorectal cancer cells. SKF-96365 hydrochloride alleviates allergic rhinitis symptoms by reducing inflammatory cytokine levels. SKF-96365 hydrochloride reduces intracellular calcium overload, inhibits Homer1 expression, prevents nuclear damage and suppresses apoptosis. SKF-96365 hydrochloride inhibits the growth of colorectal cancer xenografts in nude mice. SKF-96365 hydrochloride is applicable to research related to allergic rhinitis, colorectal cancer, Parkinson's disease, persistent spontaneous nociception and hyperalgesia.

Cyclopiazonic acid is an endoplasmic reticulum calcium ATPase (ECAs) inhibitor and human respiratory syncytial virus (RSV) inhibitor (EC₅₀ value of 4.13 μ M), which can reduce the antagonistic effect of 5-HT receptors in rat thoracic aorta, induce p53 dependent cell apoptosis and reproductive toxicity in mouse testes, and inhibit the biological activation of aflatoxin B^[1][4][5].

Penfluridol (R-16341) is a potent, long-acting, first-generation, oral diphenylbutylpiperidine antipsychotic agent by targeting D2-like dopamine receptor. Penfluridol effectively inhibits TNFα-induced NF-κB activation and alleviates the severity of arthritis and colitis in vivo. Penfluridol is a Ca2+-calmodulin inhibitor. Penfluridol induces apoptosis and autophagy. Penfluridol is used for chronic schizophrenia, acute psychosis, Tourette syndrome and autoimmune diseases. Penfluridol inhibites the growth of E. faecalis planktonic cells with the MIC of 7.81 μg/ml.