Heart Failure

LM-189 is a β₂-adrenergic receptor (β₂AR) ligand and G protein-biased modulator with a human β₂AR K_i of 0.063 nM.LM-189 promotes β₂AR coupling to Gαs and Gαi heterotrimers, stabilizes distinct β₂AR conformations including a TM6 outward state, and increases β₂AR ICL2 dynamics.LM-189 restricts β₂AR ligand-binding pocket conformational heterogeneity, stabilizes polar ligand-receptor interaction networks, and exhibits bias toward Gαi signaling over Gαs signaling.LM-189 enabled cryo-EM structural characterization of the β₂AR-Gi complex.LM-189 can be used for the research of congestive heart failure.

Zofenoprilat is an angiotensin-converting enzyme (ACE) inhibitor with an IC₅₀ of 1.7 nM. Zofenoprilat exerts cardioprotective and renoprotective effects by inhibiting angiotensin II expression and lowering blood pressure. Zofenoprilat promotes NO production and reduces endothelin-1 (ET-1) expression. Zofenoprilat decreases TNFα-induced ROS production and protects vascular endothelial function. Zofenoprilat regulates oxidative stress-related molecules and possesses antioxidant activity. Zofenoprilat can be used in studies related to hypertension and congestive heart failure.

Amisometradine is an orally active aminouracil diuretic with a diuretic potency approximately 40% that of Mersalyl (HY-108868) (when administered intramuscularly). Amisometradine exerts its effects by promoting the excretion of sodium, chloride and a small amount of potassium, exhibits significant therapeutic effects in heart failure models, and has good tolerance with long-term administration. Compared with drugs of the same class, Amisometradine causes fewer gastrointestinal reactions; its minor side effects mainly include nausea, vomiting, diarrhea, tinnitus and deafness, and are usually not accompanied by proteinuria or abnormalities in blood and urine indicators. Amisometradine is an important tool for the study of heart failure and related diuretic mechanisms.

Xamoterol (Corwin; ICI 118587) is an orally active and selective β₁-adrenoceptor partial agonist. Xamoterol acts as agonist at low sympathetic tone, antagonist at high sympathetic tone, with context-dependent cardiovascular effects including modulated heart rate, blood pressure, and cardiac output. Xamoterol can be used for the research of heart failure, postural hypotension, and ischemic heart disease.

GSK3395879 is a TRPV4 antagonist that acts on hTRPV4 with an IC₅₀ of 1 nM. GSK3395879 blocks agonist-induced TRPV4-mediated Ca²⁺ mobilization. GSK3395879 inhibits rat pulmonary edema induced by the TRPV4 agonist GSK1016790A (HY-19608). GSK3395879 can be used in research related to heart failure.

(R)-Efonidipine ((R)-NZ-105) is an orally active, selective T-type Ca²⁺ channel blocker. (R)-Efonidipine does not inhibit high-voltage-activated Ca²⁺ channels, voltage-dependent Na⁺ channels, or Ca²⁺-activated K⁺ channels. (R)-Efonidipine modulates cardiac autonomic function by increasing parasympathetic activity and decreasing sympathetic activity. (R)-Efonidipine significantly improves survival in a mouse model of dilated cardiomyopathy. (R)-Efonidipine can be used in research on ischemic encephalopathy, heart failure, and hypertension.

Carbazeran citrate is a phosphodiesterase inhibitor. Carbazeran citrate is oxidized by aldehyde oxidase/AOX1 to 4-oxo-Carbazeran citrate/hydroxyCarbazeran citrate, serving as an AOX1 probe and competitively inhibiting xanthine oxidase. Carbazeran citrate can be used in research on congestive heart failure and chronic heart failure.

Imarikiren hydrochloride (AK-272) is an orally active, selective Renin inhibitor with an IC₅₀ value of 2.1 nM against h-Renin. Imarikiren hydrochloride blocks the conversion of Angiotensinogen to Angiotensin I and reduces mean arterial pressure by inhibiting Angiotensin II that binds to AT1. Imarikiren hydrochloride alleviates myocardial hypertrophy and pulmonary congestion, exerting cardioprotective effects. Imarikiren hydrochloride can be used in research related to hypertension and heart failure.

Imarikiren (AK-272 free base) is an orally active, selective Renin inhibitor with an IC₅₀ value of 2.1 nM against h-Renin. Imarikiren blocks the conversion of Angiotensinogen to Angiotensin I and reduces mean arterial pressure by inhibiting Angiotensin II that binds to AT1. Imarikiren alleviates myocardial hypertrophy and pulmonary congestion, exerting cardioprotective effects. Imarikiren can be used in research related to hypertension and heart failure.

pUR4 is a recombinant peptide that acts as a fibronectin (FN) inhibitor. pUR4 binds to the N-terminal type I modules of fibronectin, inhibiting the polymerization of soluble fibronectin and its deposition into the extracellular matrix (ECM). pUR4 reduces β1 integrin activation by depleting ECM fibronectin and disrupting FN-β1 integrin coupling. pUR4 attenuates TNF-α-induced endothelial hyperpermeability, maintains endothelial monolayer integrity, and reduces TNF-α-induced cell morphological changes. pUR4 decreases neutrophil adhesion to cardiac endothelial cells, T cell interstitial migration, immune cell infiltration, collagen deposition, and fibroblast activation. pUR4 can be used in research on pathological vascular leakage, heart failure, inflammation, chronic kidney disease, liver fibrosis, and intestinal fibrosis.

Conivaptan-d₄ (YM 087-d₄) is the deuterated-labeled Conivaptan (HY-18347). Conivaptan (YM 087 free base) is an orally active dual vasopressin V_1a/V₂ receptor antagonist with K_i values of 0.48 nM and 3.04 nM for vasopressin V_1a receptor and V₂ receptor, respectively. Conivaptan competitively and reversibly blocks vasopressin-mediated antidiuresis, vasoconstriction, and cellular hypertrophy, while inhibiting CYP3A4. Conivaptan inhibits vasopressin-induced intracellular calcium, cAMP, and mitogen-activated kinase activation in vascular smooth muscle cells and cardiomyocytes. Conivaptan induces water diuresis while improving hemodynamics in heart failure models, reducing left ventricular end-diastolic pressure, vascular resistance, and organ weight. Conivaptan is used for research on hyponatremia and congestive heart failure.

P-gp-IN-37 is a ligand of P-glycoprotein (P-gp), with an EC₅₀ value of 1.8 μM. P-gp-IN-37 stabilizes the inward-facing conformation of P-gp through hydrogen bonding and π-stacking interactions, and can be used as a PET radiotracer for imaging the function and expression of P-gp. P-gp-IN-37 is applied in the research of heart failure.

Tonlamarsen (ION-904) is a GalNAc-conjugated antisense oligonucleotide and Angiotensinogen synthesis inhibitor. Tonlamarsen specifically reduces the production of Angiotensinogen in the liver and plasma, and exhibits extremely low activity in the kidneys. Tonlamarsen can be used in research related to hypertension and heart failure.

Tonlamarsen (ION-904) sodium is a GalNAc-conjugated antisense oligonucleotide and Angiotensinogen synthesis inhibitor. Tonlamarsen sodium specifically reduces the production of Angiotensinogen in the liver and plasma, and exhibits extremely low activity in the kidneys. Tonlamarsen sodium can be used in research related to hypertension and heart failure.

Olprinone (Loprinone) hydrochloride hydrate is a potent and selective phosphodiesterase 3 (PDE3) inhibitor, with IC₅₀ values of 150, 100, 0.35, and 14 μM against PDE1, PDE2, PDE3, and PDE4, respectively. Olprinone hydrochloride hydrate exerts comprehensive protective effects including anti-inflammatory, antioxidant, and anti-apoptotic activities by elevating intracellular cAMP levels and inhibiting the NF-κB and MAPK signaling pathways. Olprinone hydrochloride hydrate can be used in studies related to lung injury, spinal cord injury, heart failure, myocardial ischemia-reperfusion injury, and cerebral ischemic injury.

(R)-Balcinrenone ((R)-AZD9977) is an isomer of Balcinrenone (HY-120274). Balcinrenone is an orally active mineralocorticoid receptor modulator. Balcinrenone regulates mineralocorticoid receptor activity, inhibits aldosterone-induced target gene expression, and suppresses the activities of renal Toll-like receptor 4, MyD88 and NF-κB. Balcinrenone alleviates renal extracellular matrix remodeling, inflammatory cell infiltration, and the expression of renal injury markers. Balcinrenone restores myocardial perfusion reserve, regulates potassium homeostasis, and induces fecal potassium excretion. Balcinrenone is applicable to research on metabolism-related chronic kidney disease and heart failure.

Human UGT2B4 is a UDP-glucuronosyltransferase. UGT2B4 catalyzes the glucuronidation of bile acids, Carvedilol (HY-B0006) and 6-hydroxylated bile acids to form glucuronide derivatives. UGT2B4 participates in the inactivation of endogenous and exogenous substances, including catechol estrogens, C19 steroids, phenols and monoterpenoids. Human UGT2B4 can be used in the research of hypertension, angina pectoris, chronic heart failure and intrahepatic cholestasis.

CNP analogue-1 is a long-acting, low-isoelectric point C-type natriuretic peptide (CNP) analog. CNP analogue-1 activates human natriuretic peptide receptor 2 (hNPR2) with an EC₅₀ of 0.18 nM. CNP analogue-1 stimulates cGMP production and is resistant to neprilysin-mediated degradation. CNP analogue-1 induces baroreceptor-mediated heart rate elevation and enhances the maximal rates of cardiac contraction and relaxation. CNP analogue-1 can be used in the research of heart failure with preserved ejection fraction.

Hyaluronidase 2 (EC:3.2.1.35; HYAL2) is a hyaluronidase. Hyaluronidase 2 cleaves high-molecular-weight hyaluronan into intermediate, ~20 kDa, and tetrasaccharide fragments. Hyaluronidase 2 directly interacts with CD44 and ERM proteins, reduces CD44 hyaluronan binding capacity and ERM activation. Hyaluronidase 2 can be used for the research of gliomas, inflammatory bowel disease, congenital heart defects, heart failure.

GSK3491943 is an antagonist of the transient receptor potential vanilloid subtype 4 (TRPV4) ion channel. GSK3491943 is applicable to research related to pulmonary edema induced by heart failure.