Calcium Channel Inhibitor

CALP3, a Ca²⁺-like peptide, is a potent Ca²⁺ channel blocker that activates EF hand motifs of Ca²⁺-binding proteins. CALP3 can functionally mimic increased [Ca²⁺]_i by modulating the activity of Calmodulin (CaM), Ca²⁺ channels and pumps. CALP3 has the potential in controlling apoptosis in diseases such as AIDS or neuronal loss due to ischemia.

14-Deoxyandrographolide is a diterpene with calcium channel blocking activity and acts as a uterine smooth muscle relaxant. 14-Deoxyandrographolide stimulates the release of nitric oxide (NO) in endothelial cells. 14-Deoxyandrographolide gradually desensitizes liver cells to TNF-α mediated apoptosis by inducing the release of TNFRSF1A.

Cinepazide Maleate (MD-67350) is a piperazine derivative and acts as a weak calcium channel blocker. Cinepazide Maleate is a potent vasodilator and can be used for the research of cerebrovascular diseases, including ischemic stroke, brain?infarct et. al.

Trimebutine is a multi-target inhibitor and opioid receptor agonist with antimuscarinic activity. Trimebutine inhibits L-type Ca²⁺ channels and large-conductance calcium-activated potassium channels (BK_Ca channels), thereby inhibiting extracellular calcium influx and potassium ion efflux. Trimebutine also targets Toll-like receptors, inhibits Toll-like receptor 2/4/7/8/9 signals, and inhibits LPS-induced IRAK1 activation, as well as ERK1/2, JNK and NF-κB activation, thereby exerting anti-inflammatory effects. Trimebutine also induces tumor cell apoptosis by inhibiting the AKT/ERK pathway. Trimebutine also inhibits excessive contraction of smooth muscle and can be used in the study of gastrointestinal disorders such as irritable bowel syndrome (IBS).

Trimebutine maleate is a multi-target inhibitor and opioid receptor agonist with antimuscarinic activity. Trimebutine maleate inhibits L-type Ca²⁺ channels and large-conductance calcium-activated potassium channels (BK_Ca channels), thereby inhibiting extracellular calcium influx and potassium ion efflux. Trimebutine maleate also targets Toll-like receptors, inhibits Toll-like receptor 2/4/7/8/9 signals, and inhibits LPS-induced IRAK1 activation, as well as ERK1/2, JNK and NF-κB activation, thereby exerting anti-inflammatory effects. Trimebutine maleate also induces tumor cell apoptosis by inhibiting the AKT/ERK pathway. Trimebutine maleate also inhibits excessive contraction of smooth muscle and can be used in the study of gastrointestinal disorders such as irritable bowel syndrome (IBS).

Levobunolol (l-Bunolol) hydrochloride is a non-selective β-adrenergic antagonist and vasodilator. By blocking calcium ion influx and reducing the sensitivity of vascular smooth muscle to calcium, Levobunolol hydrochloride effectively dilates the ciliary arteries and increases ocular blood flow, so it is widely used in research on glaucoma and ocular hypertension. Levobunolol hydrochloride inhibits the β-receptor signaling pathway and the expression of related proliferation markers (such as CK3, CK14, CK19, Ki67) in corneal cells. In rabbit models, Levobunolol hydrochloride not only does not inhibit corneal epithelial regeneration, but also accelerates the healing of mechanical injury without adverse effects. Levobunolol hydrochloride also inhibits histamine-induced vasoconstriction and intracellular calcium elevation, exhibiting unique vascular regulatory activity. Levobunolol hydrochloride protects ocular blood flow and promotes corneal repair.

Levamlodipine ((S)-Amlodipine; Levoamlodipin) is an orally active L-type calcium channel blocker and MMP-9 modulator with high permeability and retention properties. Levamlodipine significantly enhances plaque stability and improves lipid profiles by reducing blood pressure, decreasing systolic blood pressure variability, and inhibiting MMP-9 expression in atherosclerotic plaques. Levamlodipine not only alleviates cardiac and aortic hypertrophy and prevents renal atrophy, but also produces synergistic effects in blood pressure reduction and organ protection when combined with bisoprolol (HY-129029). Levamlodipine exerts no significant inhibitory effect on abdominal aortic intimal hyperplasia. When excessively accumulated in the epidermis, Levamlodipine may induce changes in keratin structure, impair the skin barrier and trigger inflammation; long-term use further exacerbates skin irritation caused by local administration. Levamlodipine can be used in research related to hypertension and atherosclerosis.

Efonidipine (NZ-105) hydrochloride monoethanolate is an orally active dual L-type and T-type calcium channel blocker (CCB) with IC₅₀ values of 1.8 and 350 nM, respectively. Efonidipine hydrochloride monoethanolate inhibits SARS-CoV-2 main protease. Efonidipine hydrochloride monoethanolate modulates adrenal steroidogenesis by increasing the expression of steroidogenic acute regulatory protein (StAR), dbcAMP-or angiotensin II-induced StAR mRNA expression and DHEA-S production, while suppressing the biosynthesis of aldosterone and cortisol. Efonidipine hydrochloride monoethanolate reduces plasma aldosterone levels in vivo. Efonidipine hydrochloride monoethanolate improves cardiac function in heart failure models by inhibiting T-type calcium channels (via both tonic and use-dependent blockade), independently of blood pressure reduction. Efonidipine hydrochloride monoethanolate can be used for research in hypertension, heart failure, and disorders involving dysregulated steroid hormone synthesis.

IPrAuCl (compound 3) is a gold compound. IPrAuCl inhibits sarcoplasmic reticulum Ca²⁺-ATPase (IC₅₀=16.3 µM).

Ethaverine hydrochloride is a Papaverine derivative and vasodilator. Ethaverine hydrochloride inhibits Phosphodiesterase, Tyrosine hydroxylase, and MAO-B. Ethaverine hydrochloride blocks L-type Ca²⁺ channels, reduces intracellular Ca²⁺ levels, inhibits platelet adhesion and aggregation, regulates cardiac conduction and heart rate, and increases peripheral and cerebral blood flow. Ethaverine hydrochloride alters cochlear microcirculation, intracochlear Po₂, CM potential, and EP in guinea pigs, and induces transient hypotension. Ethaverine hydrochloride is used in the research of peripheral vascular diseases.

Butamben (Butyl 4-aminobenzoate) results in long-lasting relief from pain, without impairing motor function or other sensory functions.

NecroX-5 is a derivative of the NecroX, reduces intracellular calcium concentration, and possesses anti-inflammatory and anti-cancer activity.

2,5-Di-tert-butylhydroquinone (BHQ) (Compound 2), an indirect food additive, is a Sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA) inhibitor with an IC₅₀ of 400 nM. 2,5-Di-tert-butylhydroquinone disrupts the gating function of the residue Glu309 which prevents Ca²⁺ from reaching their binding site. 2,5-Di-tert-butylhydroquinone regulates the activity of 5-lipoxygenase and COX-2 (IC₅₀: 1.8 and 14.1 μM for 5-LO and COX-2, respectively).

Azimilide (NE-10064) dihydrochloride is a class III antiarrhythmic agent, which works by blocking potassium channels in the heart. Azimilide dihydrochloride is a dual blocker of I_Ks (IC₅₀ = 2.6 μM (2mM [K⁺]ₑ)) and I_Kr (IC₅₀ = 1 μM (4 mM [K⁺])). Azimilide dihydrochloride blocked HERG channel at 0.1 and 1 Hz with IC₅₀s of 1.4 μM and 5.2 μM respectively. Azimilide dihydrochloride also inhibits L-type calcium current (I_Ca) (IC₅₀ = 17.8 μM) and sodium current (I_Na) (IC₅₀ = 19 μM). Azimilide dihydrochloride can be used for the study of atrial fibrillation and ventricular fibrillation.

TROX-1 is a selective, orally active and brain-penetrant N-type calcium channel (Cav2.2) inhibitor with an IC₅₀ value of 0.11 μM. TROX-1 exerts state-dependent and use-dependent inhibition, preferentially targets open/inactivated channels, blocks depolarization-associated calcium influx, and fully blocks calcium influx in rat dorsal root ganglion neurons. TROX-1 reverses inflammatory-induced hyperalgesia, nerve injury-induced allodynia. TROX-1 can be used for the research of pain.

Azimilide (NE-10064) is a class III antiarrhythmic agent, which works by blocking potassium channels in the heart. Azimilide is a dual blocker of I_Ks (IC₅₀ = 2.6 μM (2mM [K⁺]ₑ)) and I_Kr (IC₅₀ = 1 μM (4 mM [K⁺])). Azimilide blocked HERG channel at 0.1 and 1 Hz with IC₅₀s of 1.4 μM and 5.2 μM respectively. Azimilide also inhibits L-type calcium current (I_Ca) (IC₅₀ = 17.8 μM) and sodium current (I_Na) (IC₅₀ = 19 μM). Azimilide can be used for the study of atrial fibrillation and ventricular fibrillation.

Norfluoxetine is the active metabolite of the antidepressant Fluoxetine (HY-B0102); it is also a TREK-2 K₂P potassium channel inhibitor. Norfluoxetine exhibits neuroimmunological activity, induces apoptosis in primary microglial cells, and inhibits the release of pro-inflammatory factors. Norfluoxetine inhibits high-threshold voltage-gated Ca²⁺ currents in neurons with an EC₅₀ of 20.4 μM. Norfluoxetine can be used in research related to depression, ischemic stroke, and epilepsy.

ITH12575, a CGP37157 derivative, is a potent and selective mNCX blocker. ITH12575 reduces Ca²⁺ influx through CALHM1 at low micromolar concentrations.

Prenylamine is a calcium channel blocker of the amphetamine chemical class. Prenylamine can be used as a vasodilator and can be used for the research of angina pectoris.

L-Ascorbic acid-¹³C is the ¹³C-labeled L-Ascorbic acid. L-Ascorbic acid (L-Ascorbate), an electron donor, is an endogenous antioxidant agent. L-Ascorbic acid inhibits selectively Cav3.2 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.