human cardiac

Mavacamten (MYK-461) is an orally bioavailable inhibitor of cardiac myosin ATPase,( IC50s of 490, 711 nM for bovine cardiac and human cardiac, respectively)

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.

Human cardiac troponin (mixture) (cTn) is a regulatory protein critical for muscle contraction, located on the thin filaments of the contractile proteins. It plays a significant role in controlling muscle contraction and relaxation.

Angiotensin II is a major biologically active vasoconstrictor peptide that regulates blood pressure by binding to AT1R and AT2R receptors. It stimulates the sympathetic nervous system, promotes aldosterone synthesis, and enhances renal function. Additionally, it induces vascular smooth muscle cell proliferation and increases collagen synthesis, leading to vascular and myocardial hypertrophy and fibrosis. It also promotes apoptosis and endothelial capillary formation. Angiotensin II is commonly used to induce hypertension and cardiac hypertrophy animal models.

MIV-247 is a selective and potent inhibitor of cathepsin S (Kis 2.1, 4.2, and 7.5 nM for human, mouse, and wild monkey cathepsin S, respectively), which attenuates mechanical anomalies in preclinical models of neuropathic pain, and can be used to study cardiac muscle injury.

GS-6201 (CVT-6883) is a selective antagonist of the adenosine A2B receptor, demonstrating high affinity and selectivity with a Ki of 22 nM for human adenosine A2B receptors.

Halofantrine hydrochloride (SKF-102886) is an orally administered antimalarial drug effective against drug-resistant P. falciparum and P. vivax. SKF-102886 has cardiac toxicity, inhibiting hERG and delayed rectifier potassium channel I Kr, leading to prolonged QTc and PR intervals.

ALK5-IN-82 is a potent and selective inhibitor of activin receptor-like kinase 5 (ALK5), demonstrating an IC50 value of 9.1 nM. This compound effectively suppresses the expression of α-smooth muscle actin (α-SMA), collagen I, and the proteinases tissue inhibitor of metalloproteinase 1 (TIMP-1) and matrix metalloproteinase 13 (MMP-13) in human umbilical vein endothelial cells induced by transforming growth factor-β. ALK5-IN-82 shows potential for use in research related to cardiac fibrosis.

Pyrocatechol sulfate, a phenolic metabolite found in human plasma, is associated with the intake of specific foods such as berries and the state of the gut microbiome. It serves as a potential urinary biomarker for kidney function, dialysis clearance rates, whole grain consumption, and regular coffee intake. Additionally, in conjunction with other phenolic sulfates, pyrocatechol sulfate plays a role in regulating various biological functions, including those related to brain health and the rhythmic beating of cardiac cells.

Adekalant (also known as H 345/52) is an innovative antiarrhythmic compound characterized by minimal proarrhythmic activity. It blocks HERG-mediated currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC50) of 230 nM. Adekalant binds preferentially to open channels and exhibits rapid kinetic behavior, being trapped when channels close. Its voltage-independent properties have been observed during square pulse and action potential clamp protocols. Research suggests that delaying the repolarization of human cardiac muscle through I(Kr) blockage is the primary mechanism of Adekalant’s action. It effectively blocks I(Kr) while having relatively low efficacy in blocking I(Ca), delaying ventricular repolarization without significantly increasing temporal or spatial dispersion and without inducing early afterdepolarizations or torsades de pointes (TdP).

Uridine triphosphate (UTP) is a purine nucleotide P2U receptor agonist with potential use in lung cancer treatment. By activating P2Y2 receptors, it enhances the proliferation of human cancerous ductal epithelial cells. Additionally, UTP induces fibrotic responses in cardiac fibroblasts through P2Y2 receptor activation and prolongs the action potential duration of guinea pig papillary muscles via the P2Y2 purinergic receptor.

KY02111 facilitates differentiation of hPSCs to cardiomyocytes by inhibiting Wnt signaling, maybe affect downstream of GSK3β and APC.

Urotensin-II receptor antagonist-1 (compound 1) is a human Urotensin II receptor antagonist with low oral bioavailability (F=0-3% in rats) and a Ki of 16 nM in HEK293 cells expressing human recombinant UT receptors. It inhibits cytochrome P450 enzymes (IC50=0.75 μM for CYP2D6; 1.4 μM for CYP3A4), suppresses κ opioid receptors (EC50=3.2 μM), and targets cardiac sodium channels (Ki=2.5 μM).

Norquetiapine (N-Desalkylquetiapine) is a metabolite of Quetiapine and acts as a selective HCN1 channel inhibitor with an IC50 of 13.9 μM. It selectively inhibits norepinephrine reuptake and serves as a partial agonist at the 5-HT1A receptor (Ki = 45 nM). Norquetiapine also functions as an antagonist at presynaptic α2 (Ki = 237 nM), 5-HT2C (Ki = 107 nM), and 5-HT7 (Ki = 76 nM) receptors. Additionally, it blocks human cardiac sodium channels Nav1.5 in a state-dependent manner. In LPS-injected C57BL/6 mice, Norquetiapine displays partial anti-inflammatory effects. This compound is utilized in research related to depression and inflammation.

AM-0883 is an agonist of TRPC6 (transient receptor potential canonical 6) with a human TRPC6 EC50 of 46 nM. It is applicable for research in cardiac and renal diseases.

EL244 is an inhibitor of Autotaxin (ATX) with an IC50 of 50 nM and an agonist of PPARγ with an IC50 of 1.3 μM and a Kd of 1.3 μM. In human HepG2 cells, EL244 exhibits low cytotoxicity with an EC50 of 81.2 μM and minimal inhibition of cardiac hERG potassium channels (12% at 25 μM). In vivo, EL244 significantly reduces pulmonary lysophosphatidic acid levels, alleviates fibrosis, restores respiratory function, and has limited systemic absorption. EL244 is suitable for research on idiopathic pulmonary fibrosis.

1. Crebanine iv 5mg/kg can eonvert BaCl_2-induced arrhythmia into sinus rhythm in rats, and can significantly increase the tolerant dose of aconitine to produce ventrieular fibrillation(VF) and cardiac arrest (CA) in rata. 2. Crebanine can also decrease t

Epothilone F is a derivative or analogue of Epothilone D. Epothilone F is also an active metabolite of Epothilone D. In molecule of Epothilone F, a hydroxymethyl group is on the thiazole ring. Like taxanes, Epothilone F prevents cancer cells from dividing

Neuropeptide Y (NPY) (3-36) is a C-terminal fragment of NPY, a neuropeptide involved in controlling appetite, blood pressure, cardiac contractility, and intestinal secretion. NPY (3-36) is an endogenous peptide produced by cleavage of NPY by dipeptidyl peptidase 4 (DPP-4). It binds selectively to the NPY receptor Y2 (Ki = 0.41 nM in CHP 234 cells) over the Y1 receptor, where it does not bind at concentrations up to 1 μM. NPY (3-36) (0.1 nM) increases migration of human umbilical vein endothelial cells (HUVECs) by 80% after 12 hours in an in vitro wound closure assay. NPY (3-36) corresponds to residues 3-36 of the human and rat protein sequence.

N-Desbutyl dronedarone is an active metabolite of the antiarrhythmic agent dronedarone .1,2,3It is formed from dronedarone by cytochrome P450s (CYPs) and monoamine oxidase (MAO) in human hepatocyte preparations.4N-Desbutyl dronedarone inhibits the binding of 3,3',5-triiodo-L-thyronine to the thyroid hormone receptors TRα1and TRβ1(IC50s = 59 and 280 μM for the chicken and human receptors, respectively).1It inhibits CYP2J2-mediated formation of 14,15-EET from arachidonic acid and soluble epoxide hydrolase-mediated formation of 14,15-DHET from 14,15-EET (IC50s = 1.59 and 2.73 μM, respectively, in cell-free assays).2N-Desbutyl dronedarone decreases intracellular ATP levels in H9c2 rat cardiomyocytes (IC50= 1.07 μM) and inhibits mitochondrial complex I, also known as NADH dehydrogenase, and mitochondrial complex II, also known as succinate dehydrogenase, activities in isolated rat heart mitochondria (IC50s = 11.94 and 24.54 μM, respectively).3 1.Van Beeren, H.C., Jong, W.M.C., Kaptein, E., et al.Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-α1: in vitro and in vivo evidenceEndocrinology144(2)552-558(2003) 2.Karkhanis, A., Tram, N.D.T., and Chan, E.C.Y.Effects of dronedarone, amiodarone and their active metabolites on sequential metabolism of arachidonic acid to epoxyeicosatrienoic and dihydroxyeicosatrienoic acidsBiochem. Pharmacol.146188-198(2017) 3.Karkhanis, A., Leow, J.W.H., Hagen, T., et al.Dronedarone-induced cardiac mitochondrial dysfunction and its mitigation by epoxyeicosatrienoic acidsToxicol. Sci.163(1)79-91(2018) 4.Klieber, S., Arabeyre-Fabre, C., Moliner, P., et al.Identification of metabolic pathways and enzyme systems involved in the in vitro human hepatic metabolism of dronedarone, a potent new oral antiarrhythmic drugPharmacol. Res. Perspec.2(3)e00044(2014)

17R(18S)-EpETE is an oxylipin and a cytochrome P450 metabolite of eicosapentaenoic acid. 17R(18S)-EpETE activates large-conductance calcium-activated potassium (BKCa) channels, increasing potassium current amplitude by 15-fold in isolated rat cerebral artery vascular smooth muscle cells at +60 mV at 50 nM. 17R(18S)-EpETE also exerts negative chronotropic effects in neonatal rat cardiomyocytes with an EC50 of ~1–2 nM and prevents calcium-induced increases in spontaneous beating. 17R(18S)-EpETE is therefore used in cardiovascular electrophysiology research systems to investigate ion channel modulation, lipid mediator signaling, and cardiac excitability regulation in cellular models.

(R)-Fadrozole ((R)-CGS 16949A; FAD286) is a potent nonsteroidal inhibitor. (R)-Fadrozole also inhibits human placental aromatase (pIC 50 = 6.17) and aldosterone biosynthesis. (R)-Fadrozole reverses cardiac fibrosis in spontaneously hypertensive heart failure rats..

TM5441 is an orally bioavailable fibrinogen activator inhibitor-1 inhibitor that inhibits several cancer cell lines with IC50 values ranging from 13.9 to 51.1 μM.It induces intrinsic cell death in several human cancer cells and attenuates Nω-nitro-1-arginine methyl ester-induced cardiac hypertension and vascular senescence.

(Rac)-Indoximod (1-Methyl-DL-tryptophan) is a potent inhibitor of indoleamine 2,3-dioxygenase (IDO). Combined treatment with IFN-γ and (Rac)-Indoximod significantly suppresses the activity of α-SMA-expressing human cardiac myofibroblasts (hCMs) and promotes apoptosis by up-regulating the genes IRF-1, Fas, and FasL, effectively improving cardiac fibrosis[1].