cardiac fibroblasts

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.

Enalaprilat (Enalapril acid) is a potent angiotensin-converting enzyme (ACE) inhibitor that enhances arterial and cardiopulmonary pressure reflex control of sympathetic activity in patients with heart failure, and can be used in the study of cardiovascular disease.

ATX inhibitor 5 is a potent and orally active autotaxin (ATX) inhibitor (IC50: 15.3 nM) that reduces CCl4-induced hepatic fibrosis and exhibits anti-hepatic fibrosis effects.

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.

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.

Autotaxin-IN-7 (45) is a pyridine-2-carboxylic acid derivative exhibiting sub-nanomolar inhibition of ATX (IC50 = 0.086 nM) and features excellent cardiac safety (hERG > 30 μM) with minimal toxicity to fibroblasts. It inhibits the TGF-β/Smad signaling pathway, reducing α-smooth muscle actin (α-SMA) and extracellular matrix components (ECM). Autotaxin-IN-7 (45) can be used in pulmonary fibrosis research.

sGC stimulator 1 is a carbonyl sulfide (COS)/H2S donor hybrid soluble guanylate cyclase (sGC) stimulator with an EC50 of 496 nM. It demonstrates significant H2S release properties and reduces fibrosis in cardiac fibroblasts treated with TGF-β1 by increasing H2S levels. sGC stimulator 1 exerts antifibrotic effects by activating sGC and elevating H2S concentrations. This compound is applicable for heart failure (HF) research[1].

MIPS3526 is a potent and selective A2B adenosine receptor (A2BR) agonist, exhibiting a pEC50 value of 10.17 (with an EC50 of 58 pM). It demonstrates high receptor subtype selectivity against A1R, A2AR, and A3R. MIPS3526 mitigates the stimulatory effects of angiotensin II on cardiomyocytes and fibroblasts and is useful in studying cardiovascular diseases, particularly heart failure driven by cardiac remodeling.

TK-129 is an orally active, potent inhibitor of KDM5B with an IC50 of 44 nM and is low-toxicity. TK-129 exhibits cardioprotective effects by inhibiting KDM5B and blocking the KDM5B-associated Wnt pathway. TK-129 can be used in cardiovascular disease studies to reduce isoprenaline-induced myocardial remodelling and fibrosis in vivo, as well as to reduce ang II-induced activation of cardiac fibroblasts in vitro [1].

DCN1-UBC12-IN-2 is a potent and specific DCN1-UBC12 inhibitor with an IC50 value of 9.55 nM, targeting DCN1-UBC12 interactions and inhibiting Ang II-induced activation of cardiac fibroblasts.

11-Dehydrocorticosterone is a metabolite of glucocorticoids, a sodium-retaining agent that increases SGK mRNA expression in cardiac fibroblasts and dose-dependently inhibits aldosterone.

Angiotensin II human TFA is a potent vasoconstrictor in the renin-angiotensin system that regulates blood pressure through interactions with AT1R and AT2R receptors. It activates sympathetic nerve activity, promotes aldosterone synthesis and renal function, induces proliferation of vascular smooth muscle cells, and enhances type I and III collagen production in fibroblasts, leading to vascular and myocardial thickening and fibrosis. It also triggers apoptosis and promotes capillary formation, making it suitable for establishing models of cardiac hypertrophy, hypertension, and abdominal aortic aneurysm.

Mitochonic acid 5 (MA-5) is a derivative of the plant hormone indole-3-acetic acid. Mitochonic acid 5 binds mitochondria and ameliorates renal tubular and cardiac myocyte damage.It has been shown to improve survival of fibroblasts from patients with mitochondrial diseases.

Moexiprilat, an active metabolite of the prodrug moexipril formed through side chain ester hydrolysis in vivo, functions as an angiotensin-converting enzyme (ACE; IC50 = 2.1 nM) inhibitor. At a concentration of 10 nM, it inhibits the proliferation of primary neonatal rat cardiac fibroblasts stimulated by estrone or angiotensin II. Furthermore, when given at a daily dosage of 50 mg/kg, moexiprilat reduces mean arterial blood pressure and elevates levels of atrial natriuretic peptide, an indicator of hypertension, in ovariectomized mice.

LSD1-IN-34 (Compound 7d) is an orally effective inhibitor of lysine-specific demethylase (LSD) and monoamine oxidase (MAO), exhibiting IC50 values of 4.51 nM for LSD1 and 18.46 nM for MAO A. This compound inhibits activation of neonatal rat cardiac fibroblasts (NRCF) induced by angiotensin II (Ang II) and shows no significant toxicity at 20 μM. LSD1-IN-34 also inhibits the TGFβ/Smad signaling pathway, contributing to the improvement of heart failure in mice. Moreover, it demonstrates favorable pharmacokinetic properties in rats.

Selective PAR2 peptide antagonist. Reverses taxol-induced mechanical allodynia, heat hyperalgesia and PKC activation in ICR mice. Blocks ERK activation and collagen production in isolated cardiac fibroblasts. Also reduces symptoms in a mouse model of derm

FSLLRY-NH2 TFA is a is a protease-activated receptor 2 (PAR2) inhibitor. Reverses taxol-induced mechanical allodynia, heat hyperalgesia and PKC activation in ICR mice. Blocks ERK activation and collagen production in isolated cardiac fibroblasts. Also reduces symptoms in a mouse model of dermatophyte-associated itch.

C-Type Natriuretic Peptide (1-53), from porcine, rat, and mouse sources, serves as an activator of particulate guanylate cyclase B (pGC-B), prominently found in endothelial cells, kidneys, and the heart. This peptide efficiently mediates a potent anti-fibrotic effect in human cardiac and renal fibroblasts through the production of the second messenger cGMP.

T3 Peptide is an active fragment of tumstatin. By binding to integrins αvβ3/αvβ5, it activates the PI3K/Akt/p70S6K signaling pathway, thereby promoting the proliferation and migration of rat cardiac fibroblasts.

SVVYGLR is a peptide derived from osteopontin. It facilitates the differentiation of fibroblasts into myofibroblast-like cells and enhances the production of type III collagen by cardiac fibroblasts. In vitro, SVVYGLR activates endothelial cell adhesion, migration, and tube formation. Additionally, it promotes angiogenesis, wound healing, and the migration of dermal fibroblasts and keratinocytes. SVVYGLR is applicable in studies related to angiogenesis, dermal wounds, and bone regeneration.