Table 2.
Summary of calcium signaling pathway drugs.
| Target | Target type | Disease | Drugs | KEGG pathway | |
|---|---|---|---|---|---|
| 1 | Adenosine A1 receptor (ADORA1) | Clinical trial target | Orthostatic hypotension | Caffeine (Rosenthal et al., 2008); Tonapofylline (Chen and Tang, 2007) | Calcium signaling pathway; Rap1 signaling pathway; cAMP signaling pathway; neuroactive ligand-receptor interaction; vascular smooth muscle contraction; Parkinson's disease; alcoholism |
| 2 | Adenosine A2a receptor (ADORA2A) | Clinical trial target | Coronary artery disease | Apadenoson; Binodenoson(Hodgson et al., 2007) | Calcium signaling pathway; Rap1 signaling pathway; cAMP signaling pathway; neuroactive ligand-receptor interaction; vascular smooth muscle contraction; Parkinson's disease; alcoholism |
| 3 | Adenosine A2b receptor (ADORA2B) | Clinical trial target | Hypertension | YT-146 (T et al., 1994) | Calcium signaling pathway; Rap1 signaling pathway; neuroactive ligand-receptor interaction; vascular smooth muscle contraction; alcoholism |
| 4 | Adenosine A2b receptor (ADORA2B) | Successful target | Paroxysmal supraventricular tachycardi; reperfusion injury | Adenosine (Xin et al., 2020) | Calcium signaling pathway; Rap1 signaling pathway; neuroactive ligand-receptor interaction; vascular smooth muscle contraction; alcoholism |
| 5 | Adrenergic receptor beta-1 (ADRB1) | Successful target | Hypertension; reperfusion injury | Metoprolol (Qin et al., 2020) | Calcium signaling pathway; cGMP-PKG signaling pathway; cAMP signaling pathway; neuroactive ligand-receptor interaction; endocytosis; adrenergic signaling in cardiomyocytes; gap junction; salivary secretion; dilated cardiomyopathy |
| 6 | Angiotensin II receptor type-1 (AGTR1) | Successful target | Hypertension | Valsartan (Chang et al., 2020) | Calcium signaling pathway; cGMP-PKG signaling pathway; neuroactive ligand-receptor interaction; adrenergic signaling in cardiomyocytes; vascular smooth muscle contraction; renin-angiotensin system; renin secretion; pathways in cancer |
| 7 | Calcium channel unspecific (CaC) | Successful target | Cerebral vasospasm; hyperinsulinemia | Nimodipine (G and M, 2009) | Calcium signaling pathway; MAPK signaling pathway; cardiac muscle contraction; |
| 8 | Calcium-activated potassium channel KCa1.1 (KCNMA1) | Literature-reported target | Asthma | Cromoglycate lisetil hydrochloride (Law et al., 2011) | Calcium signaling pathway; cGMP-PKG signaling pathway; vascular smooth muscle contraction; Insulin secretion; salivary secretion; pancreatic secretion |
| 9 | Calcium-release activated calcium channel (CRACM) | Clinical trial target | Non-Hodgkin lymphoma | RP4010 (Cui et al., 2018) | Calcium signaling pathway; cAMP signaling pathway; platelet activation; primary immunodeficiency |
| 10 | Calpain-2 (CAPN2) | Clinical trial target | Cerebral infarction | ABT-957 (Ge et al., 2005) | Protein processing in endoplasmic reticulum; apoptosis; calcium signaling pathway; Alzheimer's disease |
| 11 | CaM-kinase II (CAMK2) | Clinical trial target | Anxiety disorder | Rimacalib (J et al., 2009) | Calcium signaling pathway; ErbB signaling pathway; cAMP signaling pathway; HIF-1 signaling pathway; Wnt signaling pathway; circadian entrainment; neurotrophin signaling pathway; cholinergic synapse; Inflammatory mediator regulation of TRP channels; Insulin secretion; GnRH signaling pathway; melanogenesis; oxytocin signaling pathway; glucagon signaling pathway; gastric acid secretion |
| 12 | Endothelin A receptor (EDNRA) | Successful target | Cerebrovascular disease; hypotension | Ambrisentan (Rosenzweig, 2006) | Calcium signaling pathway; cGMP-PKG signaling pathway; cAMP signaling pathway; neuroactive ligand-receptor interaction; vascular smooth muscle contraction; renin secretion; pathways in cancer |
| 13 | Nitric-oxide synthase endothelial (NOS3) | Clinical trial target | Pulmonary hypertension; brain injury | Tilarginine acetate (Investigators et al., 2007) | Calcium signaling pathway; arginine and proline metabolism; Metabolic pathways; cGMP-PKG signaling pathway; HIF-1 signaling pathway; sphingolipid signaling pathway; PI3K-Akt signaling pathway; VEGF signaling pathway; platelet activation; estrogen signaling pathway; oxytocin signaling pathway |
| 14 | Proteinase activated receptor 1 (F2R) | Successful target | Myocardial infarction | Vorapaxar (Maki et al., 2010) | Calcium signaling pathway; Rap1 signaling pathway; cAMP signaling pathway; neuroactive ligand-receptor interaction; endocytosis; PI3K-Akt signaling pathway; complement and coagulation cascades; platelet activation; regulation of actin cytoskeleton; pathways in cancer |
| 15 | S100 calcium-binding protein B (S100B) | Clinical trial target | Stroke; type 2 diabetes; | ONO-2506 (Asano et al., 2005) | Calcium signaling pathway; cGMP-PKG signaling pathway; neuroactive ligand-receptor interaction endocytosis; salivary secretion |
| 16 | Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A) | Successful target | Malaria | Artemisinin (Choia et al., 2008) | Calcium signaling pathway; pyrimidine metabolism; metabolic pathways |
| 17 | Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (ATP2A2) | Clinical trial target | Hypertension; asthma | Gallopamil (Sulpizio et al., 2005) | Calcium signaling pathway; renin-angiotensin system; Alzheimer's disease; adrenergic signaling in cardiomyocytes; Thyroid hormone signaling pathway; Alzheimer's disease; hypertrophic cardiomyopathy (HCM); arrhythmogenic right ventricular cardiomyopathy (ARVC); dilated cardiomyopathy |
| 18 | Sodium/calcium exchanger (SLC) | Clinical trial target | Cardiovascular disease | CALDARET HYDRATE(Kawasumi et al., 2007) | Calcium signaling pathway; cardiac muscle contraction; adrenergic signaling in cardiomyocytes; |
| 19 | Sodium/hydrogen exchanger 1 (SLC9A1) | Clinical trial target | Myocardial infarction; angina pectoris | Zoniporide hydrochloride(Tracey et al., 2003) | Calcium signaling pathway; cAMP signaling pathway; cardiac muscle contraction; adrenergic signaling in cardiomyocytes; regulation of actin cytoskeleton; thyroid hormone signaling pathway; salivary secretion; gastric acid secretion; pancreatic secretion; bile secretion; proteoglycans in cancer |
| 20 | Thromboxane A2 receptor (TBXA2R) | Successful target | Acute myocardial infarction | Ridogrel(Xavier,Davel,Fukuda and Rossoni 2009) | Calcium signaling pathway; neuroactive ligand-receptor interaction; platelet activation |
| 21 | Voltage-gated calcium channel alpha Cav1.2 (CACNA1C) | Successful target | Hypertension | Rauwolfia serpentina root(Wiens and De Luca, 2016) | Calcium signaling pathway; MAPK signaling pathway; cGMP-PKG signaling pathway; cAMP signaling pathway; cardiac muscle contraction; adrenergic signaling in cardiomyocytes; vascular smooth muscle contraction; circadian entrainment; type II diabetes mellitus; hypertrophic cardiomyopathy (HCM); Arrhythmogenic right ventricular cardiomyopathy (ARVC); dilated cardiomyopathy |
| 22 | Voltage-gated calcium channel alpha Cav1.2 (CACNA1C) | Clinical trial target | Alzheimer disease | ARC029 (H et al., 1989) | Calcium signaling pathway; MAPK signaling pathway; cGMP-PKG signaling pathway; cAMP signaling pathway; cardiac muscle contraction; adrenergic signaling in cardiomyocytes; vascular smooth muscle contraction; circadian entrainment; Insulin secretion; type II diabetes mellitus; hypertrophic cardiomyopathy (HCM); arrhythmogenic right ventricular cardiomyopathy (ARVC); dilated cardiomyopathy |
| 23 | Voltage-gated calcium channel alpha Cav2.1 (CACNA1A) | Successful target | Cardiac failure; reperfusion injury | Flunarizine (Wulff et al., 2019) | Calcium signaling pathway; MAPK signaling pathway; synaptic vesicle cycle; retrograde endocannabinoid signaling; glutamatergic synapse; long-term depression; type II diabetes mellitus; morphine addiction; nicotine addiction |
| 24 | Voltage-gated calcium channel alpha Cav2.2 (CACNA1B) | Successful target | Pain; traumatic brain injury | Ziconotide (Xiong et al., 2009) | Calcium signaling pathway; MAPK signaling pathway; synaptic vesicle cycle; retrograde endocannabinoid signaling; GABAergic synapse; dopaminergic synapse; taste transduction; type II diabetes mellitus |
| 25 | Voltage-gated calcium channel alpha Cav3.1 (CACNA1G) | Successful target | Hypertension; Insomnia; | Verapamil (TD et al., 2005) | Calcium signaling pathway; MAPK signaling pathway; circadian entrainment; type II diabetes mellitus |
| 26 | Voltage-gated calcium channel alpha Cav3.2 (CACNA1H) | Successful target | Metabolic acidosis; migraine | Sodium bicarbonate (Wood et al., 2009) | Calcium signaling pathway; MAPK signaling pathway; circadian entrainment |
| 27 | Voltage-gated calcium channel alpha-2/delta-1 (CACNA2D1) | Successful target | Hypertension | Diltiazem (Huang et al., 2009); Amlodipine (Ram, 2009) | Calcium signaling pathway; MAPK signaling pathway; cardiac muscle contraction; adrenergic signaling in cardiomyocytes; Oxytocin signaling pathway; hypertrophic cardiomyopathy (HCM); arrhythmogenic right ventricular cardiomyopathy (ARVC); dilated cardiomyopathy |
| 28 | Voltage-gated calcium channel alpha-2/delta-1 (CACNA2D1) | Successful target | Chronic obstructive pulmonary disease | Pregabalin (Andrade, 2018) | Calcium signaling pathway; MAPK signaling pathway; cardiac muscle contraction; Adrenergic signaling in cardiomyocytes; Oxytocin signaling pathway; hypertrophic cardiomyopathy (HCM); arrhythmogenic right ventricular cardiomyopathy (ARVC); dilated cardiomyopathy |
| 29 | Voltage-gated L-type calcium channel (L-CaC) | Successful target | Angina pectoris; hypertension | Nifedipine (Kleinsasser and Loeckinger, 2002); Nisoldipine; Levamlodipine(Oh et al., 2012) | Calcium signaling pathway; MAPK signaling pathway; Cardiac muscle contraction; |
| 30 | Voltage-gated L-type calcium channel (L-CaC) | Clinical trial target | Cardiovascular disease | BAY-Y-5959 (GH et al., 1998) | Calcium signaling pathway; Cardiac muscle contraction; |