systolic

Finerenone (BAY-948862) is a nonsteroidal antagonist of the mineralocorticoid receptor (MR) (IC50=18 nM) with selective and oral activity. Finerenone is used in the treatment of patients with chronic kidney disease with type 2 diabetes.

Danicamtiv (MYK-491) is an inotropic agent and it also is a selective allosteric activator of cardiac myosin. Danicamtiv increases cardiac systolic function and preserves mechanical efficiency.

SERCA2a activator 1 is a sarco/endoplasmic reticulum Ca2+-dependent ATPase 2a activator. SERCA2a activator 1 decreases phospholamban inhibition and enhances the systolic and diastolic functions of the heart.

Strophanthidin (Strophanthidine) can induce calcium overload in vivo.

Eplerenone (CGP 30083) is an aldosterone receptor antagonist and potassium-sparing diuretic used in the therapy of hypertension. Eplerenone therapy has been associated with transient elevations in serum aminotransferase levels, but has yet to be linked to cases of clinically apparent drug induced liver disease.

Allicin exerts antioxidant, bactericidal, anti-cancer, anti-inflammatory activities, it exerts an inhibitory immunomodulatory effect on intestinal epithelial cells. Allicin could significantly inhibit vascular smooth muscle cells' proliferation and migration induced by insulin, which may be related to the inhibition of the activation of ERK signal path. Allicin is beneficial in reducing blood cholesterol, triglycerides levels and systolic blood pressure in hypercholesterolemic rats, it may beneficially affect two risk factors for atherosclerosis-hyperlipidemia and hypertension.

DL-Homocysteine thiolactone hydrochloride (DL-Homocysteinethiolactone hydrochloride) is a cysteine derivative that binds to and induces conformational changes in various plasma proteins, slowing coagulation and inducing oxidative stress. It decreases left ventricular systolic blood pressure and cardiac force and induces seizures in vivo.

Alagebrium chloride (ALT711) is an advanced glycation end product (AGE) inhibitor that has proven effective in reducing systolic blood pressure and providing therapeutic benefits for patients with diastolic.

Afurolol Hydrochloride (DL 071-IT) is a non-selective β-adrenergic receptor antagonist. DL 071 IT exhibits intrinsic sympathomimetic activity, reducing exercise heart rate, systolic blood pressure, and resting heart rate.

KR-32568 is a sodium/hydrogen exchanger 1 (NHE-1) inhibitor (IC50: 230 nM) with potent cardioprotective effects. At a concentration of 10 μM, it restored cardiac systolic function in an isolated ischemic rat heart model. Additionally, KR-32568 (0.3 mg/kg) reduced myocardial infarction size in a rat model of ischemia and reperfusion injury.

Adrenochrome (Adraxone) is a cytotoxic molecule that can be used to kill bacteria. Adrenochrome is an oxidized product of Epinephrine. Adrenochrome is a coronary systolic compound that acts on rat hearts and is associated with cardiotoxicity and can be used to determine superoxide dismutase activity. Adrenochrome is a potential psychotropic drug for the study of nervous system diseases.

Ulacamten, also known as CK-4021586 or CK-586, is an orally bioavailable and highly selective cardiac myosin inhibitor that enhances the transition of myosin into a force-generating state without altering calcium handling, demonstrating sub-micromolar biochemical potency and improving left ventricular systolic function in preclinical models while maintaining myocardial energetic efficiency and minimizing off-target activity against skeletal and smooth muscle myosin.

NHE-1-IN-2 (compound 7g) is a potent NHE-1 inhibitor with an IC50 of 0.78 μM. It mitigates left ventricular systolic dysfunction in mouse models of heart failure.

Mopidralazine hydrochloride (MDL-899) (Compound 30) is an orally active antihypertensive agent. It significantly reduces systolic blood pressure in spontaneous hypertensive rat models with an ED50 value of 1.94 mg/kg. In renal hypertensive dog models, Mopidralazine hydrochloride acts more slowly but has a longer duration of effect and significantly less impact on heart rate increase. It is utilized in hypertension research.

Pyrazinoylguanidine (PZG) is an analogue of the potassium-sparing diuretic amiloride. It can reduce systolic and diastolic blood pressure in patients with primary hypertension and has a slight effect on reducing heart rate without altering serum concentrations of electrolytes such as sodium, potassium, or chloride. Pyrazinoylguanidine also alleviates hyperglycemia and hyperinsulinemia in type 2 diabetes patients, lowers triglycerides, cholesterol, and free fatty acids, and can reverse the hyperglycemia and hyperlipidemia induced by thiazide diuretics like hydrochlorothiazide. Additionally, it inhibits renal tubular reabsorption of urea, enhancing urea clearance and excretion, thus reducing serum urea concentration and its toxic accumulation.

AD-9308 is a highly selective, orally active ALDH2 activator. By activating ALDH2, it enhances the clearance of 4-HNE and inhibits myocardial fibrosis, inflammation, and apoptosis. AD-9308 improves mitochondrial function, regulates sarcoplasmic/endoplasmic reticulum calcium transport, and modulates autophagy, thereby restoring intracellular homeostasis. It improves diastolic and systolic dysfunction in diabetic mice and reverses adverse ventricular remodeling. AD-9308 is useful for studying diabetic cardiomyopathy.

P-536 is an ACE inhibitor that concurrently inhibits the thymidine kinase of herpes simplex virus (HSV-1) and the RNA polymerase of Trypanosoma cruzi. By suppressing the renin-angiotensin system, downregulating AT1R and NOX4 expression, and decreasing oxidative stress (lowering plasma hydrogen peroxide (H2O2) and 8-isoprostane levels), P-536 effectively reduces systolic blood pressure and enhances vascular reactivity. Additionally, P-536 hinders the replication of DNA/RNA viruses such as HSV-1 by blocking nucleotide metabolism and nucleic acid synthesis; it competitively inhibits Trypanosoma cruzi RNA synthesis, suppresses epimastigote replication, and thereby obstructs their growth. P-536 is applicable in the research of hypertension, insulin resistance, and Chagas disease.

A-80b is a synthesized pyridazino[4,5-b]indole derivate with potent and long-lasting antihypertensive activity. The decrease in diastolic pressure was greater than the decrease in systolic pressure and cardiac frequency was not modified significantly. A-8

AAA is an antagonist of G protein-coupled receptor 75 (GPR75).1It increases basal GPR75 protein levels and inhibits 20-HETE-induced reductions in GPR75 protein levels in PC3 cells. AAA (5 and 10 μM) also reduces 20-HETE-induced phosphorylation of EGFR, NF-κB, and Akt in, and cell migration of, PC3 cells.In vivo, AAA (10 mg/kg per day) reduces systolic blood pressure, albuminuria, renal angiotensin II levels, and cardiac hypertrophy in a Cyp1a1-Ren-2 transgenic rat model of malignant hypertension when administered prior to induction or after establishment of hypertension.2 1.Cárdenas, S., Colombero, C., Panelo, L., et al.GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cellsBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(2)158573(2020) 2.Sedláková, L., Kikerlová, S., Husková, Z., et al.20-Hydroxyeicosatetraenoic acid antagonist attenuates the development of malignant hypertension and reverses it once established: a study in Cyp1a1-Ren-2 transgenic ratsBiosci. Rep.38(5)BSR20171496(2018)

5-methyl-2-HOBA is an isoketal scavenger. It reduces angiotensin II-induced increases in systolic blood pressure in mice.

C2 Ceramide (d14:1/2:0) is a bioactive sphingolipid that, when administered dietarily at 100 μM, induces lipotoxic cardiomyopathy by increasing diastolic and systolic diameter, reducing fractional shortening, and decreasing the number of normal cardiac contractile events in Drosophila.

Quazinone is a selective inhibitor of phosphodiesterase 3 (PDE3) with positive inotropic and vasodilating properties. It induces relaxation of precontracted isolated human cavernous smooth muscle (IC50 = 4.2 μM), increases myocardial contractile force in anesthetized open-chest dogs in a dose-dependent manner (10-300 μg/kg), decreases systolic and diastolic blood pressure, and inhibits DNA synthesis induced by the PDGF isoform PDGF-BB in bovine coronary artery smooth muscle cells in a concentration-dependent manner.

CXL-1020, a nitroxyl (HNO) prodrug, enhances cardiac inotropy/lusitropy and Ca 2+ cycling in rats exhibiting abnormal relaxation, induces vasorelaxation, and augments cardiac function in canine models. It has been investigated for its potential in treating systolic and stable heart failure [1].

Lorundrostat (MT-4129) is an aldosterone synthase inhibitor with antihypertensive activity that lowers systolic blood pressure.