calcium signaling

Dantrolene is a postsynaptic muscle relaxant by inhibiting Ca2+ ions release from sarcoplasmic reticulum stores by antagonizing ryanodine receptors.

5-(N,N-Hexamethylene)-amiloride (5-HMA) is an amiloride derivative that inhibits TRPA1-mediated calcium signaling (IC50: 35 μM). It functions as an inhibitor of the Na+/H+ exchanger (NHE) with Ki values ranging from 0.013 to 2.4 μM for various NHE isoforms. Additionally, 5-HMA blocks ASIC3 channels by 51% at 20 μM.

Bifenthrin is a synthetic pyrethroid insecticide.Bifenthrin induces cell death in bovine mammary epithelial cells through ROS generation, disruption of calcium homeostasis, and alteration of the MAPK signaling cascade.Bifenthrin induces apoptosis by inducing cell-cycle arrest.

2-Aminoethyl diphenylborinate (2-APB) is a cell-permeable inhibitor of IP3R and TRP channels. 2-Aminoethyl diphenylborinate also inhibits store-operated Ca2+ (SOC) channels and activates certain TRP channels (V1, V2, and V3). 2-Aminoethyl diphenylborinate also inhibits vasospasm. 2-Aminoethyl diphenylborinate can be used in research on calcium biology, cell signaling, oncology, and neurobiology.

Addition of the Rhamnose (6-Deoxy-L-mannose)-rich polysaccharide, RROP-1, to normal human dermal fibroblasts (NHDFs) and human endothelial cells produced a dose-dependent stimulation of the calcium-signaling pathway, inducing fast and transient increases in Ca2 influx and intracellular free Ca2 level.

CXCR4 antagonist 6 (compound 46) is a highly potent small-molecule inhibitor of the chemokine receptor CXCR4 with an IC50 value of 79 nM, effectively suppressing CXCL12-induced cytosolic calcium flux with an IC50 of 0.25 nM, significantly inhibiting CXCL12/CXCR4-mediated cell migration, and demonstrating pronounced therapeutic efficacy in a mouse model of cancer metastasis, highlighting its value for cancer biology, metastasis research, and chemokine signaling studies.

FLA-99 is a biochemical compound that selectively inhibits the enzymatic breakdown of inositol-1,4,5-triphosphate (IP3) by inositol-1,4,5-triphosphate 5-phosphatase. By preventing IP3 degradation, FLA-99 modulates intracellular calcium signaling, making it a useful tool in signal transduction and phosphoinositide pathway research.

Carboxyamidotriazole Orotate (L-651582 Orotate) is a cytostatic inhibitor of non-voltage-operated calcium channels and associated signaling pathways. As the orotate salt form of Carboxyamidotriazole (CAI), it is an orally bioavailable signal transduction inhibitor with in vitro antileukaemic activity, exhibiting anti-tumor, anti-inflammatory, and antiangiogenic effects.

Ethacrynic acid, a diuretic, functions as an inhibitor of L-type voltage-dependent and store-operated calcium channels, facilitating the relaxation of airway smooth muscle (ASM) cells. It exhibits anti-inflammatory effects, notably reducing retinoid-induced ear edema in mice, and inhibits glutathione S-transferases (GSTs), making it a potent suppressor of the NF-kB signaling pathway. Additionally, ethacrynic acid modulates leukotriene formation. A variant, Ethacrynic acid-D5, is distinguished by its deuterium labeling.

Ganoderic acid F exhibits antitumor and antimetastatic activities through inhibition of angiogenesis and alteration of proteins involving cell proliferation and/or cell death, carcinogenesis, oxidative stress, calcium signaling, and endoplasmic reticulum

Jasmonic acid (JA) is a phytohormone and plant growth regulator involved in plant defense and growth and development.Jasmonic acid plays an important role in signaling, inducing the MAP kinase cascade pathway and calcium channels.

Murrayafoline A is a natural carbazole alkaloid found primarily in plants of the genera Murraya and Glycosmis. Murrayafoline A directly targets Specific Protein 1 (Sp1), thereby inhibiting the NF-κB and MAPK signaling pathways. Murrayafoline A attenuates the Wnt/β-catenin pathway by promoting the degradation of intracellular β-catenin. Murrayafoline A induces G0/G1 phase arrest in platelet-derived growth factor (PDGF)-stimulated vascular smooth muscle cells. Murrayafoline A enhances contractility and L-type calcium currents in rat ventricular myocytes by activating protein kinase C. Murrayafoline A inhibits LPS-induced neuroinflammation in vivo. Murrayafoline A can be used in research on inflammation, vascular complications, and colorectal cancer.

BHPI is a potent inhibitor of nuclear estrogen receptor ERα–regulated gene expression that induces sustained ERα-dependent activation of the endoplasmic reticulum stress sensor and unfolded protein response, leading to persistent inhibition of protein synthesis, and in ERα-positive cancer cells it hyperactivates plasma membrane PLCγ to generate IP3, deplete ER calcium stores via IP3R channels, and convert the normally protective UPR into a toxic response, making BHPI a valuable probe for estrogen signaling and ER stress–based cancer research.

Carboxyamidotriazole is a cytostatic inhibitor of non-voltage-operated calcium channels and calcium channel-mediated signaling pathways. It shows anti-inflammatory, anti-tumor, and antiangiogenic effects.

ADWX 1 TFA is a novel peptide that potently targets and inhibits the Kv1.3 channel, with an IC50 of 1.89 pM. It specifically suppresses the activity of the Kv1.3 channel, in addition to inhibiting initial calcium signaling and NF-κB activation. This compound has been shown to ameliorate symptoms in rats with experimental autoimmune encephalomyelitis (EAE). ADWX 1 TFA is utilized in research focused on T-cell-mediated autoimmune diseases.

BRI-50460 is an inhibitor of cytosolic calcium-dependent phospholipase A2 (cPLA2) with the ability to cross the blood-brain barrier, exhibiting an IC50 of 0.88 nM. By inhibiting cPLA2, BRI-50460 modulates downstream inflammatory lipid signaling pathways, mitigating the effects of amyloid β42 oligomers on cPLA2 activation, tau protein hyperphosphorylation, and synaptic and dendritic loss. This results in its activity in regulating neuroinflammation and restoring lipid homeostasis. BRI-50460 is applicable in research related to Alzheimer's disease and other neurodegenerative disorders.

FLY26 is a selective partial antagonist of GluN2B, with an IC50 value of 0.64 μM. FLY26 inhibits the GluN2B subunit of NMDA receptors, reducing calcium ion influx and reactive oxygen species (ROS) production. It also activates the BDNF/TrkB/CREB neuroprotective signaling pathway, mitigating excitotoxicity and mitochondrial dysfunction. FLY26 holds potential for treating neurological deficits caused by cerebral ischemia-reperfusion injury.

Mrgx2 antagonist-3 (Compound B-40) is a highly selective antagonist of the MrgX2 receptor, with an IC50 range of 0.042-2.5 nM. It blocks downstream G protein signaling and β-arrestin recruitment, inhibiting Mrgx2 receptor-mediated calcium influx and cell degranulation. Mrgx2 antagonist-3 shows potential for research in inflammation-associated diseases and pruritus, such as chronic urticaria and allergic asthma.

GPR84agonist-2 (Compound 8e) is a highly selective GPR84 agonist with an EC50 value of 7.24 nM. It activates the Gαq signaling pathway, leading to the production of inositol triphosphate (IP3) and the release of calcium ions. This compound enhances the chemotaxis of neutrophils and the release of pro-inflammatory cytokines, making it a promising candidate for research into inflammatory diseases such as ulcerative colitis and acute lung injury.

Picolinafen is a pyridine herbicide that functions as an inhibitor of phytoene desaturase (PDS) and is utilized for its ability to manage the growth of broadleaf weeds by disrupting carotenoid biosynthesis. It exhibits cytotoxicity towards porcine trophoblast cells (pTr) and porcine luminal epithelial cells (pLE). By inducing the accumulation of reactive oxygen species (ROS), depleting calcium, and activating MAPK and PI3K signaling pathways, Picolinafen leads to reduced cell viability, increased apoptosis, impaired migration abilities, and altered expression of implantation-related genes, ultimately affecting the implantation capability of pTr cells. The LD50 value of Picolinafen for mammals is 2.7 mg/kg, and it is 7 μg/L for fish. Additionally, Picolinafen shows toxic effects during zebrafish embryonic development.

5-HT2C agonist-11 (Compound 1) is an orally active, brain-penetrant, and selective 5-HT2C receptor agonist with an EC50 of 15 nM. It activates the Gq protein signaling pathway, promoting intracellular calcium release. This compound shows potential for research in depression, post-traumatic stress disorder (PTSD), and neuropathic pain.

GSNOR-IN-1 is a prodrug of GSNOR-IN-2 and functions as an S-nitrosoglutathione reductase (GSNOR) inhibitor capable of crossing the blood-brain barrier. GSNOR-IN-1 offers significant protective effects against damage induced by oxygen-glucose deprivation/reoxygenation (OGD/R). It regulates calcium signaling and synaptic function through Clstn1 S-nitrosylation and inhibits neuronal apoptosis. Additionally, GSNOR-IN-1 markedly reduces infarct volume in rat models of ischemic stroke while enhancing neurological function. With its neuroprotective properties, GSNOR-IN-1 holds potential for ischemic stroke research.

AXT-914 is an inhibitor of the calcium-sensing receptor (CaSR). It exhibits antiviral activity against coronaviruses HCoV 229E and SARS-CoV2. AXT-914 reduces cytoplasmic calcium signaling activity caused by CaSR mutations. It is applicable in research on Bartter syndrome type 5, autosomal dominant hypocalcemia (ADH), and coronavirus infections.

(Rac)-Ibrutinib alkyne (Compound 8) is a Btk inhibitor with an IC50 of 0.72 nM. This compound effectively inhibits B cell receptor signaling functions, with an IC50 of 9 nM for calcium flux inhibition in Ramos cells. (Rac)-Ibrutinib alkyne is applicable in research on diseases such as rheumatoid arthritis.