cardiac hypertrophy

Zonisamide (AD 810), a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

20-HETE promotes cell proliferation and migration in cancer and can be used to study prostate tumors and cardiac hypertrophy by activating the protein kinase C pathway to increase FBXO10 expression.

Enrasentan (sb-217242) is a mixed antagonist of ET(A) and ET(B) receptors that reduces blood pressure, prevents cardiac hypertrophy, and protects myocardial function.

GSK 2833503A is a potent and selective TRPC6 and TRPC3 antagonist (IC50 = 3-16 nM and 21-100 nM, respectively). GSK 2833503A exhibits >63-fold selectivity over other ion channels, including other TRP channels, CaV1.2, hERG and NaV1.5. GSK 2833503A suppresses angiotensin II or endothelin-1-induced cardiac hypertrophy signaling in HEK293 cellsin vitroand in cardiomyocytes.

Trimethylamine N-oxide dihydrate (TMANO dihydrate) is a gut microbiota-dependent metabolite derived from dietary choline and other trimethylamine-containing nutrients. It induces inflammation by activating the ROS/NLRP3 inflammasome and promotes fibroblast differentiation and cardiac fibrosis via the TGF-β/Smad2 signaling pathway. TMANO dihydrate can be used to establish models of cardiac hypertrophy and cardiac fibrosis.

L002, a potent, cell-permeable, reversible, and specific acetyltransferase p300 (KAT3B) inhibitor with an IC50 of 1.98 μM, directly binds the acetyl-CoA pocket and competitively inhibits the FATp300 catalytic domain. By blocking histone acetylation, p53 acetylation, and STAT3 activation, L002 shows potential in the treatment of hypertension‐induced cardiac hypertrophy and fibrogenesis.

Enrasentan (also known as SB-217242) is a dual receptor endothelin antagonist with a higher affinity for the ET(A) receptor. In animal models of hypertension and cardiac hypertrophy, this compound reduces blood pressure, prevents cardiac hypertrophy, and preserves myocardial function. Enrasentan enhances survival rates, limits left ventricular remodeling, and maintains myocardial performance in hypertensive cardiac hypertrophy and dysfunction.

ERBB agonist-1 (Compound EF-1) is an ERBB4 agonist (EC50=10.5 μM) that induces ERBB4 receptor dimerization and phosphorylation of Akt and ERK1/2. It exhibits cardioprotective effects in mouse models and prevents myocardial fibrosis.

Delocamten is an inhibitor of cardiac myosin, with an IC50 value of 1.1 μM. It is useful in research on hypertrophic cardiomyopathy, left ventricular hypertrophy, and diastolic dysfunction.

Phosphodiesterase-IN-2 (Compound C7) is an orally active and selective inhibitor of phosphodiesterase 10A (PDE10A), with an IC50 of 11.9 nM. It enhances hepatic microsomal stability and reduces blood-brain barrier permeability. Phosphodiesterase-IN-2 exhibits favorable pharmacokinetic properties in mouse models and can alleviate isoprenaline-induced cardiac hypertrophy.

ZAK-IN-1 is an orally active and selective inhibitor of the leucine zipper and sterile-alpha motif kinase ZAK, with an IC50 of 4 nM and a KD of 8 nM. It demonstrates exceptional selectivity against 403 types of wild-type kinases. ZAK-IN-1 effectively blocks the p38/GATA-4 and JNK/c-Jun signaling pathways, significantly suppressing cardiac hypertrophy. This compound is applicable in the study of hypertrophic cardiomyopathy (HCM).

AH001 is an orally active compound that binds to a concealed pocket near GDP within RhoA, exhibiting a binding affinity of 73.16 nM. By interacting with GDP, AH001 stabilizes the interaction between RhoA and its endogenous inhibitor, RhoGDIα. This compound reduces nuclear translocation of downstream MRTFA and downregulates fibrosis/hypertrophy-related proteins. AH001 alleviates myocardial remodeling in various heart failure animal models and 3D cardiac tissue models. Its cardioprotective effects are mediated through the RhoA-RhoGDIα axis, effectively inhibiting downstream RhoA activation signals.

SGLT2-IN-2 (Compound E9) is an inhibitor of SGLT2 and significantly enhances the inhibition of SGLT2, NHE1, and SOD enzyme activities. It provides protection against myocardial cell damage induced by glucose-free DMEM. Additionally, SGLT2-IN-2 markedly improves cardiac function in TAC-induced heart failure (HF) mice, suppressing myocardial cell hypertrophy and collagen deposition. It reduces myocardial tissue damage and boosts autophagy in damaged myocardial cells, increasing the survival rate of HF mice.

Mitotic kinesin-IN-3 (Page 135, fourteenth) hydrochloride is an inhibitor of the mitotic motor protein (Mitotickinesin). It interferes with cell proliferation by inhibiting mitosis. This compound can be utilized in research relating to cancer, cardiac hypertrophy, immune and inflammatory diseases, as well as fungal infections.

Mitotic kinesin-IN-2 (Page 135, fifteenth) hydrochloride is an inhibitor of mitotic motor proteins (Mitotickinesin). This compound suppresses cell proliferation by inhibiting mitosis. Mitotic kinesin-IN-2 hydrochloride is used in research related to cancer, cardiac hypertrophy, immune and inflammatory diseases, as well as fungal infections.

Mitotic kinesin-IN-1 hydrochloride (Example 80) is an inhibitor of mitotic kinesin, which suppresses cell proliferation by hindering mitosis. This compound is applicable in research related to cancer, cardiac hypertrophy, immune and inflammatory diseases, and fungal infections.

MDL-100240 is a dual inhibitor of angiotensin-converting enzyme (ACE) and neprilysin with a balanced activity. MDL 100240 shows an impressive effectiveness both in preventing and in regressing hypertension-induced vascular remodeling and cardiac hypertrop

Syringin (eleutheroside-b) is a compound with antitumor, antiproliferative, immunomodulatory and platelet aggregation inhibiting effects.

17(S)-HETE is an arachidonic acid metabolite generated via the CYP450 pathway. 17(S)-HETE acts as an allosteric activator of CYP450 1B1 and an ATPase inhibitor, capable of inducing cardiac hypertrophy.

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)

Chlorthalidone impurity G is a potential impurity found in commercial preparations of chlorthalidone that has moderate antihypertensive effects. Chlorthalidone is a thiazide-like diuretic that inhibits the Na+/Cl- cotransporter in the distal convoluted tubule of the kidney, which prevents reabsorption of sodium and chloride leading to a reduction in plasma volume and cardiac output. It also inhibits carbonic anhydrase (CA), including the isoforms CAVB, VII, IX, XII, and XIII (Kis = 2.8-23 nM) and, to a lesser extent, CAI, CAII, IV, VA, and VI (Kis = 138-1,347 nM), which may mediate its sustained vasodilatory activity. Dietary administration of chlorthalidone (8 mg per animal per day) reduces arterial hypertension and prevents or reduces ventricular hypertrophy induced by deoxycorticosterone acetate (DOCA) in salt-hypertensive rats. Formulations containing chlorthalidone have been used alone or in combination with other antihypertensive agents to lower arterial blood pressure and as adjuvants to address edema caused by cardiac or renal disorders.

19(R)-HETE is a renal artery vasodilator that can be used to study angiotensin II-induced cardiac hypertrophy.

KR-39038 is an orally active GRK5 (G protein-coupled receptor kinase 5) inhibitor (IC50: 0.02 μM) that inhibits the HDAC5 pathway in neonatal cardiomyocytes and significantly reduces angiotensin II-induced hypertrophy, leading to notable anti-myocardial hypertrophy effects and improved cardiac function. KR-39038 is applicable for heart failure research.

TUPS is a selective soluble epoxide hydrolase inhibitor which protects against isoprenaline-induced cardiac hypertrophy.