Levosimendan

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Cat Number

API141505331

CAS Number

141505-33-1

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CAS Number

141505-33-1

EINECS

663-528-6

Storage

Room Temperature (Recommended in a cool and dark place, < 15°C)

Synonyms

Simdax; (R)-Simendan; (-)-OR-1259; 2-[2-[4-[(4R)-1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl]phenyl]hydrazinylidene]propanedinitrile

Molecular Formula

C14H12N6O

Molecular Weight

280.28

Smiles

C[C@@H]1CC(=O)NN=C1C2=CC=C(C=C2)NN=C(C#N)C#N

Appearance

Yellow solid

General Description

Levosimendan, the (–)-enantiomer of 4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenylhydrazonopropanedinitrile, is a pyridazinone-dinitrile derivative. It is classified as a novel calcium enhancer characterized by its calcium-sensitizing activity.

Mechanism of Action

The principal mechanism of action identified for levosimendan is augmentation of troponin C affinity for Ca2+ with stabilization of troponin C conformation. In addition, its opening of adenosine triphosphate- (ATP-) sensitive potassium channels on the membranes of vascular smooth muscle induces intense vasodilation. In addition, its opening of mitochondrial ATP-sensitive potassium channels results in cardioprotection and causes selective phosphodiesterase inhibition.

Application

Levosimendan is primarily indicated for the short-term treatment of acutely decompensated heart failure (ADHF) in situations where conventional therapy is insufficient and inotropic support is required. Beyond chronic heart failure management, it is frequently utilized in cardiac surgery to prevent or treat low cardiac output syndrome (LCOS) and has shown promise in managing right ventricular failure and sepsis-induced myocardial dysfunction.

Levosimendan causes calcium sensitisation of cTnC, increasing myocardial contractility without a concomitant increase in intracellular calcium concentration and without augmenting myocardial oxygen consumption. Levosimendan initially and directly binds to cTnC in a calcium-dependent fashion. The N-terminal domain of cTnC is responsible for calcium-induced conformational changes which permit actin-myosin crossbridge cycling and thereby muscle contraction. The stabilisation of the cTnC calcium-bound state by levosimendan binding increases the calcium sensitivity of cTnC. Levosimendan binding to cTnC stabilizes the complex formed between cTnC and calcium, thereby increasing the time calcium remains bound to cTnC. This enhances the process of contraction by better utilizing the calcium entering the myocardial cells during each cycle of contraction, resulting in more forceful contractions without requiring an increase in the calcium concentration entering the cells.

Fig. 1 Mechanisms of Action of Levosimendan. (Susilo H, et al. 2024)

References

Susilo H, et al. Levosimendan, a promising pharmacotherapy in cardiogenic shock: A comprehensive review. European Cardiology Review. 2024, 19: e21.

Repeated administration of low-dose cisplatin (CDDP) chemotherapy causes renal fibrosis through the Mettl3-dependent pathway. The expression of Mettl3 is induced during CDDP treatment by HIF1-α, and post-treatment, through lactate-induced H3K18 lactylation, forming a positive feedback loop. Mettl3 stabilizes Pfkfb3 mRNA via m6A modification, increasing glycolysis and lactate production. Lactate upregulates PD-L1 expression in fibroblasts through histone lactylation, contributing to fibrosis. Tubule-specific Mettl3 knockout alleviates CDDP-induced renal injury in mice. Levosimendan directly inhibits Mettl3 methyltransferase activity without dissociating the Mettl3-Mettl14 complex, leading to decreased m6A levels. PLGA-encapsulated levosimendan attenuates fibrosis by inhibiting the Mettl3/Pfkfb3/lactate/H3K18la/PD-L1 axis and unexpectedly increases CDDP antitumor activity in xenograft models (ovarian, breast, bladder cancers) by downregulating PD-L1.

Fig. 2 PLGA-encapsulated levosimendan inhibition of Mettl3 alleviates low-dose cisplatin-induced renal fibrosis. (Xie Y, et al. 2025)

References

Xie Y, et al. Inhibition of Mettl3 alleviates low-dose cisplatin-induced renal fibrosis and enhances the chemotherapeutic efficacy in mouse models of cancer. International Journal of Biological Sciences. 2025, 21(10): 4293-4311.

Can Levosimendan be stored at room temperature?

While short-term exposure is fine, long-term storage of Levosimendan at room temperature is discouraged to prevent chemical degradation.

Is the Levosimendan sensitive to high humidity levels?

Yes, Levosimendan is hygroscopic and must be stored in moisture-proof sealed bags.

Will a certificate of analysis (CoA) accompany my Levosimendan order?

Yes, every batch of Levosimendan includes a detailed CoA for quality verification.

Is each batch of Levosimendan tested for residual solvents?

Yes, we perform GC testing on Levosimendan to ensure minimal residual solvents.