cardiac diseases

GSK-114, a selective inhibitor of TNNI3 Interacting Kinase (TNNI3K) with IC50 of 25 nM, shows significant bias for TNNI3K over B-Raf with IC50 of 1000 nM, exceptional broad spectrum kinase selectivity and adequate oral exposure to enable its use in cellul

AM-8123 is an orally available nonpeptide APJ agonist.AM-8123 reduces collagen load and improves cardiac function. AM-8123 ameliorates myocardial infarction in rats and can be used to study cardiovascular diseases such as heart failure.

ROCK-IN-5 (compound I-B-37) is a potent inhibitor of protein kinases, including ROCK, ERK, GSK, and AGC, with potential applications in cardiac, proliferative, and neurodegenerative disease research.

Examorelin (Hexarelin) is an agonist of growth hormone-releasing factor (GHRF), and for the treatment of cardiac diseases.

AM-001, a non-competitive inhibitor of Epac1, effectively blocks the activation of Rap1, a downstream effector of Epac1, in cultured cells, and is commonly used in heart disease-related research.

SIRT3 Activator 1 (Compound 5v) is a selective activator of SIRT3. It enhances the expression of SIRT3, leading to upregulation of SOD2 and OPA1. This activity effectively mitigates mitochondrial dysfunction, alleviates oxidative stress, and maintains the vitality of cardiac myocytes. SIRT3 Activator 1 is useful in the study of cardiovascular diseases.

BDK-IN-1 (compound (-)-43) is a BDK inhibitor with an IC50 of 0.23 μM and a maximum inhibition rate of 90%. It reduces phosphorylated-E1 levels and is useful in the study of cardiac metabolic diseases.

MRS7799 is a selective A3 Adenosine Receptor antagonist with Kd values of 0.55 nM for humans, 3.74 nM for mice, and 2.80 nM for rats. MRS7799 can be utilized in research related to neurodegenerative diseases, cancer, cardiac and cerebral ischemia, and autoimmune inflammatory diseases.

FABP4-IN-3 (Compound C3) is a highly selective inhibitor of FABP4, with an inhibition constant (Ki) of 25 ± 3 nM for FABP4 and a Ki of 15.03 μM for FABP3, showcasing a selectivity factor of 601 times over FABP3. It also demonstrates metabolic stability and potent anti-inflammatory activity in cells, making it a promising candidate for research in metabolic disorders, cardiac dysfunction, and inflammation-related diseases.

ALDH2activator 1 (Compound Z17) is an allosteric activator of aldehyde dehydrogenase 2 (ALDH2). This compound improves cardiac function and reduces myocardial necrosis in a mouse model of ischemia-reperfusion. ALDH2activator 1 holds potential for research in cardiovascular diseases, such as myocardial infarction (MI).

DPP8/9-IN-2 (Compound 21) is an inhibitor targeting DPP8 and DPP9 with IC50 values of 0.22 nM and 3 nM, and Ki values of 2.9 nM and 6 nM, respectively. It exhibits certain cardiac toxicity, with IC50 values against the hERG potassium channel, Nav1.5 sodium channel, and Cav1.2 calcium channel of 0.7 μM, 29.0 μM, and 27.7 μM. DPP8/9-IN-2 is applicable for research into diseases such as cancer.

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.

Myosin-IN-2 (Example 16) is an inhibitor of Myosin ATPase, exhibiting an IC50 value of 1.06 μM. It is applicable in research related to cardiac diseases, including hypertrophic cardiomyopathy (HCM).

VHC-7 is a potent and selective activator of adenylyl cyclase type 8 (AC8) with an EC50 of 105.2 nM. It elevates levels of cyclic adenosine monophosphate (cAMP). VHC-7 is applicable in research related to central nervous system disorders and cardiac diseases.

Multi-target kinase-IN-6 is a multi-target kinase inhibitor. It can inhibit cardiac RyR2 and NaV1.5 channels while stimulating the activity of the SERCA2a pump. Multi-target kinase-IN-6 is applicable in research on cardiovascular diseases, including heart failure.

AM-0883 is an agonist of TRPC6 (transient receptor potential canonical 6) with a human TRPC6 EC50 of 46 nM. It is applicable for research in cardiac and renal diseases.

SERCA2a activator 2 (Compound 25) is a potent activator of SERCA2a (cardiac type) and also activates SERCA1a (skeletal muscle type). Under [Ca²⁺]MAX conditions, it enhances SERCA2a ATPase activity and facilitates Ca²⁺ uptake with EC₅₀ values of 4 μM and 0.80 μM, respectively. It consistently activates under near-physiological [Ca²⁺]MID conditions as well. Furthermore, SERCA2a activator 2 exhibits low cytotoxicity, making it useful for researching diseases such as heart failure.

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.

Myosin-IN-4 (Compound 3) is a pyridine-2,4-dione derivative that acts as an inhibitor of cardiac myosin. It exhibits strong inhibitory activity against cardiac myosin ATPase, with an IC50 value of 0.73 μM. Myosin-IN-4 induces a negative inotropic effect by inhibiting myocardial contraction and is useful for research into cardiovascular diseases related to cardiac myosin.

CCG 258001 is a GRK inhibitor with IC50 values of 0.29 µM for GRK2, 51.8 µM for GRK1, and 33 µM for GRK5. It inhibits GRK activity in cardiac and other muscle cells, and is useful for researching heart diseases, such as heart failure, cardiac hypertrophy, and hypertension.

Digoxigenin, a therapeutic drug belonging to the group of cardiac glycosides, is widely used in the management of congestive heart failure and other cardiac diseases

Wnt signaling is required for direct multiple biological processes and also plays key roles in the pathogenesis of various diseases. Cyclic AMP response element-binding protein (CREB) is a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome. The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. Via generating a transcriptionally active complex with β-catenin, CREB acts as a mediator of Wnt signaling.ICG-001 is an inhibitor of β-catenin/CREB mediated transcription. The direct cellular target of ICG-001 is CREB. the inhibitory IC50of ICG-001 against β-catenin/CREB mediated transcription was 3 μM. ICG-001 treatment at the concentration of 25 μM for 24h significantly increased caspase activity in both colon cancer cell lines SW480 and HCT116 cell lines but not in normal colonic epithelial cells CCD-841Co. In a cell growth inhibition assay, the IC50s of ICG-001 against SW480 and HCT116 cells were 4.43 μM and 5.95 μM, respectively.In a SW620 nude mouse xenograft model, an water-soluble analog of ICG-001 given at the dose of 150 mg/kg i.v. once in every 2 days dramatically suppressed tumor growth. In a bleomycin-induced pulmonary fibrosis mice model, ICG-001 given at the dose of 5 mg/kg per day reversed pulmonary fibrosis. In a rat myocardial infarction model, ICG-001 was administrated subcutaneously at the dose of 50 mg/kg/day for 10 days which significantly improved cardiac contractile function after myocardial infarction in the rats.