Molecular and metabolic landscape of adenosine triphosphate-induced cell death in cardiovascular disease

Table 2 Summary of small-molecule modulators in adenosine triphosphate-induced cell death-related diseases

Drug	Mechanism	Targets	Ref.
P2X7 antagonist	Inhibit P2RX7 function	High blood pressure; atherosclerosis	[79]
IL-1β and IL-18 inhibitors	Inhibit the release of IL-1β and IL-18	Myocardial infarction and heart failure	[79]
Caspase-3 inhibitors	Inhibit the proteolysis of caspase-3	Reduces or reverses heart failure	[30]
S-propranolol	Decreased caspase-3 activity	I/R injury	[80]
Spirolactone	Inhibits alpha-adrenergic vasoconstriction in the arteries	Drug-resistant hypertension	[81]
Prosulfanilone and carbenolone	Blocking thrombin-induced calcein outflow and reducing Ca2+ inflow, ATP release, platelet aggregation, and thrombosis at the in vitro arterial shear rate	Arterial thrombus	[82]
Curcumin, resveratrol, notoginseng lactone and allicin	Inhibition of NLRP3 inflammasome	Hypertension TOD	[63]
Pubescenoside A active compound	It inhibited NLRP3 inflammatory activation and induced Nrf2 signaling pathway	I/R injury	[83]
Resveratrol (PIC)	TG storage and caspase 1 activity were inhibited	Atherosclerosis
MRS-2179	Inhibit platelet aggregation	Thrombotic syndrome	[84,85]
MRS2500	Inhibit P2RY1	Thrombus	[86]
NF157	Inhibit inositol phosphate accumulation	I/R injury	[87]
SKF96365	The entry of orai1 Ca2+ was inhibited	Atherosclerosis	[88]
ML9	Inhibition of STIM1	Hypertrophy and Ca2+ overload due to I/R; cardiomyocyte death	[89]
TDCPP	Decreased STIM1 expression of and increased GSK3β phosphorylation	I/R injury	[90]
MMPSI	Selective inhibition of caspase 3/7	Myocardial ischemic injury	[36]
Acetyl-tyr-val-ala-asp chloromethyl ketone	They blocked caspase activation	Myocardial injury induced by ischemia and reperfusion; myocardial infarction	[91]
Hypericin	Up-regulation of autophagy after myocardial infarction	Myocardial infarction	[92]
MRS-2339	Activated the heart P2X receptor	Heart failure	[93]
Propofol	Induced autophagy	I/R injury	[94]
Carvedilol	Novel vasodilator beta-adrenergic receptor antagonist and potent antioxidant	Myocardial I/R induced apoptosis	[95]
Midazolam	Inhibit p38 MAPK	Myocardial I/R injury	[96]
Ulinastatin	Inhibit inflammation, oxidative stress and apoptosis	Chronic heart failure	[97]
Kaempferol	Inhibition of ASK1	Cardiac hypertrophy	[98]
KN-93	Inhibition of NOX2	Cardiac remodeling and heart failure	[99]
Acacetin	Inhibit oxidative stress, inflammation and apoptosis	Diabetic cardiomyopathy	[100]
CETP inhibitor	Elevated phosphorylation levels of vascular myosin light chain and myosin phosphatase target subunit 1, a protein that promotes contractility, along with enhanced reactive ROS production	Hypertension	[101]
Fasudil	ROCKI inhibition	Coronary vasospasm, angina pectoris, hypertension, heart failure	[102,103]
Isosteviol (STV)	ERK1/2 is selectively activated in cells exposed to stress	Myocardial ischemia-reperfusion	[103]
Adriamycin (DOX)	Induced oxidative stress	Heart failure	[105]
Plasminogen activator inhibitor 1	Release the pro-inflammatory cytokine TNF-α	Thromboembolism complication	[106]
Rosuvastatin	MG53 up-regulation was induced	Myocarditis	[107]
Na+/H+ exchanger 1	Catalyze increased intracellular Na uptake	Hypertrophy of heart; heart failure	[108]
Prasugrel	Inhibit P2RY12	ST-segment elevation myocardial infarction following primary percutaneous coronary intervention	[109]

P2RX7: Purinergic receptor P2X7; IL: Interleukin; I/R: Ischemia/reperfusion; ATP: Adenosine triphosphate; NLRP3: NOD-like receptor family pyrin domain-containing protein 3; TOD: Target organ damage; Nrf2: NF-E2-related factor-2; P2RY1: P2Y purinoceptor 1; STIM1: Stromal interaction molecule 1; GSK: Glycogen synthase kinase; MAPK: Mitogen-activated protein kinases; ASK1: Apoptosis signal regulating kinase 1; NOX2: NADPH oxidase 2; ROS: Reactive oxygen species; ROCK I: Rho-associated, coiled-coil containing protein kinase 1; ERK1/2: Extracellular signal regulated kinase 1 and 2; TNF: Tumor necrosis factor.