cardiac hypertrophy

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.

VB124 is an orally active, potent, and selective MCT4 inhibitor, demonstrating specificity in hindering lactate efflux, with IC50 values of 8.6 nM and 19 nM for lactate import and export, respectively, in MDA-MB-231 cells. Its high selectivity for MCT4 over MCT1 positions VB124 as a promising agent for researching cardiac hypertrophy, heart failure, and metabolic disorders [1].

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.

NGD-8243 (N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]quinazolin-4-amine) is a TRPV1 inhibitor and can be used in studies for prevention and treatment of cardiac hypertrophy.

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.

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.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.

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

Tamarixetin (4'-O-Methyl Quercetin) is a natural flavonoid derivative of quercetin that exhibits anti-inflammatory and antioxidative effects, offering protection against cardiac hypertrophy.

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.

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

S6 peptide, a lamin kinase of potential importance, plays a role in the induction of cardiac hypertrophy following mechanical loading and can be activated by various growth factors [1].

VCP-746 is a potent adenosine A2B receptor agonist that stimulates anti-fibrotic signalling. VCP746 reduces hypertrophy in a rat neonatal cardiac myocyte model. VCP746 is a hybrid molecule consisting of an adenosine moiety linked to an adenosine A1 receptor (A1AR) allosteric modulator moiety. At the A1AR, VCP746 mediated cardioprotection in the absence of haemodynamic side effects such as bradycardia.

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)

Angiotensin 1-7 (Ang-(1-7)) acetate, an endogenous heptapeptide from the renin-angiotensin system (RAS), exhibits cardioprotective effects through anti-inflammatory and anti-fibrotic activities in cardiac cells. It inhibits purified canine ACE activity (IC50 = 0.65 μM) and modulates kinin-induced vasodilation by hindering ACE and facilitating nitric oxide release. This compound also prevents Ang II-induced proliferation and hypertrophy in smooth muscle cells and demonstrates antiangiogenic and growth-inhibitory effects on the endothelium [1] [2] [3].

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.

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

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.

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