cardiac fibroblasts

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.

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.

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 that activates the ERBB4 signaling pathway by inducing ERBB4 receptor dimerization, with an EC50 of 10.5 μM. It promotes phosphorylation of Akt and ERK1 2, reduces collagen expression in cardiac fibroblasts, and inhibits H2O2-induced cardiomyocyte death and Ang II-induced cardiac hypertrophy. Furthermore, ERBB agonist-1 can prevent myocardial fibrosis and demonstrates cardioprotective effects in mouse models.

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].

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.

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.

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.

DCN1-IN-2, a DCN1 inhibitor, exhibits potent activity with an IC 50 of 2.96 nM. It effectively mitigates Ang II TGFβ-induced activation of cardiac fibroblasts and diminishes ISO-induced cardiac fibrosis and remodeling in mice through the selective inhibition of cullin 3.

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.