troponin

Troponin modulator 1 (compound 7) enhances the function of mutated myocardial thin filaments. By phosphorylation, it increases Ca2+ sensitivity, with an EC50 of 67 μM.

Troponin I is a cardiac and skeletal muscle protein useful in the laboratory diagnosis of a heart attack. Troponin I is a part of the troponin protein complex, where it binds to actin in thin myofilaments to hold the actin-tropomyosin complex in place.

Human cardiac troponin (mixture) (cTn) is a regulatory protein critical for muscle contraction, located on the thin filaments of the contractile proteins. It plays a significant role in controlling muscle contraction and relaxation.

EMD57033 is a cardiac troponin C (cTnC) activator, a dominant Ca2+ sensitizer, which functions by binding to cardiac slow skeletal troponin C heterodimers to promote cardiac contraction.

Levosimendan (OR1259) is a calcium sensitizer used in the management of acutely decompensated congestive heart failure. It increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan exerts its effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner.

Reldesemtiv (CK-2127107) is a selective fast skeletal muscle troponin activator with an EC50 of 3.4 μM, enhancing exercise performance in heart failure models.

6,6′-Trehalose dioleate (6,6′-TDO) is a glycolipid extensively used for in vivo and in vitro mRNA delivery. This compound effectively encapsulates mRNA encoding hemagglutinin A (HA) from influenza A virus for use within lipid nanoparticles (LNPs), enhancing the secretion of Ifn-γ, Il-2, and Tnf-α from isolated murine spleen cells. When administered via intramuscular injection in mice, LNPs containing 6,6′-TDO predominantly accumulate in the liver and spleen. Unlike LNP formulations without 6,6′-TDO, those containing 6,6′-TDO do not reduce serum levels of blood urea nitrogen (BUN) or elevate levels of lactate dehydrogenase (LDH), troponin I, alanine aminotransferase (ALT), or aspartate aminotransferase (AST). Additionally, these LNPs enhance the serum titers of IgG1 and IgG2a antibodies in mice.

3-Cl-DPA, a cardiac troponin activator, acts by a mechanism distinct from bepridil or TFP.

GSK854 is a highly selective and potent inhibitor of troponin I interacting kinase (TNNI3K) that inhibits myocardial infarction-injured cellular pyroptosis and apoptosis in mice, which may limit oxidative stress, injury, and adverse remodeling in the ischemic heart.

Lipoxygenin is an inhibitor of 5-lipoxygenase (5-LO) with an IC50value of 5 μM for inhibition of 5-LO product synthesis in isolated human granulocytes stimulated with the cation ionophore A23187 .1It inhibits hedgehog-dependent signaling in Shh-LIGHT2 cells and TGF-β-, activin A-, bone morphogenic protein (BMP)-, or Wnt-dependent signaling in HEK293T cells (IC50s = 9.3, 3.2, 8.2, 9.6, and 3.7 μM, respectively, in luciferase reporter assays). Lipoxygenin (5 and 10 μM) increases levels of troponin T (TnnT), a marker of cardiomyocyte differentiation, in human induced pluripotent stem cells (iPSCs) stimulated with BMP4 and the glycogen synthase kinase 3 (GSK3) inhibitor CHIR99021 .

Tirasemtiv (CK-2017357)(CK 2017357) is a small-molecule fast-skeletal-troponin activator, with a potential treatment for muscle weakness and neuromuscular dysfunction.

Nelutroctiv is a potent activator of cardiac troponin.

SR-33805 is a calcium channel antagonist potentially for the treatment of atherosclerosis and heart failure. SR-33805 restored the MI-altered cell shortening without affecting the Ca(2+) transient amplitude, suggesting an increase of myofilament Ca(2+) sensitivity in MI myocytes. A SR33805-induced sensitization of myofilament activation was found to be associated with a slight increase in myosin light chain-2 phosphorylation and a more significant decrease on troponin I (TnI) phosphorylation. Decreased TnI phosphorylation was related to inhibition of protein kinase A activity by SR-33805.

Anti-MI R injury agent 1 (compound 18), derived from Panaxatriol, is an orally administered, potent agent against myocardial ischemia reperfusion (MI R) injury. It improves cell viability in cardiomyocytes subjected to oxygen-glucose deprivation and reperfusion (OGD R)-induced injury, significantly reduces myocardial infarction size, diminishes levels of circulating cardiac troponin I (cTnI), and mitigates cardiac tissue damage in rat models [1].

CK-963 is an activator of cardiac troponin (cTnC) with a K i of 11.5 μM, exhibiting activity in enhancing cardiac contractility in Sprague-Dawley rats [1].