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Sinapultide API Manufacturers & Suppliers

General Description:

Sinapultide, identified by CAS number 138531-07-4, is a notable compound with significant therapeutic applications. Sinapultide (also known as KL4 peptide) is a synthetic protein used to mimic human lung surfactant protein B. This protein has a weight of 2469.40. Sinapultide is a 21-residue peptide made up of lysine (K) and leucine (L) residues with the sequence KLLLLKLLLLKLLLLKLLLLK (KL4), in aqueous dispersion with the phospholipids DPPC (dipalmitoylphosphatidylcholine), POPG (palmitoyloleoyl-phosphatidylglycerol), and palmitic acid, to create the drug . The product was originally developed by the Scripps Research Institute, then licensed to Windtree Therapeutics. Windtree Therapeutics plans a phase III trial for Respiratory distress syndrome in 2018. Respiratory distress syndrome (RDS) is a major cause of mortality and morbidity in preterm infants. Surfactant replacement therapy has been commonly used to prevent and treat RDS in these newborns and is now a standard of care. First-generation synthetic surfactants that were previously used, such as _Exosurf_ did not contain any surfactant protein. This large disadvantage was overcome with animal-derived surfactant products which contain specific proteins but are limited, but must be derived from animal sources. This has led to the development of newer synthetic surfactants such as lucinactant (Surfaxin), which contains sinapultide. Phase 3 clinical trials with Surfaxin show promising results with similar efficacy as animal-derived surfactants while avoiding the use of animal-origin products. Windtree is currently developing aerosolized KL4 surfactant to treat RDS in premature infants, and thereafter, to potentially address a range of indications in neonatal, pediatric and adult critical care patient populations.

Indications:

This drug is primarily indicated for: Infant respiratory distress syndrome , , , . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Absorption:

The absorption characteristics of Sinapultide are crucial for its therapeutic efficacy: Administered directly to the lung, where biophysical effects occur at the terminal airways and alveolar surface. No human pharmacokinetic studies have been done to characterize the absorption, distribution, metabolism, or elimination of this drug . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Pharmacodynamics:

Sinapultide exerts its therapeutic effects through: Windtree’s KL4 surfactant technology produces a synthetic surfactant that is structurally similar to human pulmonary surfactant and contains a proprietary synthetic peptide KL4 (sinapultide), cost a 21-amino acid peptide that is formulated to mimic the essential attributes of the human surfactant protein B (SP-B). This protein is one of four surfactant proteins and is the most important for the adequate function of the respiratory system. Windtree has demonstrated in pre-clinical studies that KL4 surfactant may possess certain other beneficial properties, including alteration of the inflammatory process, antimicrobial properties as well as non-immunogenicity . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Sinapultide functions by: Endogenous pulmonary surfactant lowers surface tension at the air-liquid interface of the alveolar surfaces during respiration and stabilizes the alveoli against collapse at resting transpulmonary pressures. A deficiency of pulmonary surfactant in premature infants results in RDS. Surfaxin, the drug in which this protein is included, compensates for the deficiency of surfactant and restores surface activity to the lungs of these infants . To explore the mechanisms of protection that this sinapultide offers against RDS, in vitro assays were performed with human and murine endothelial cell monolayers, and polymorphonuclear leukocyte (PMN) transmigration in the presence or absence of KL(4)-surfactant or lipid controls was studied. Based on morphology, histopathology, white blood cell count, percentage of PMNs, and protein concentration in bronchoalveolar lavage fluid, the results that showed KL(4)-surfactant, blocked neutrophil influx into alveoli and thus prevented lung injury. Additionally, in vitro assays demonstrated KL(4)-surfactant decreased neutrophil transmigration at the endothelial cell level. KL(4)-surfactant diminished inflammation and lung permeability when compared with controls in both mouse models of lung injury. Evidence suggests the anti-inflammatory mechanism of the KL(4)-peptide is achieved through inhibition of PMN transmigration through the endothelium . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Categories:

Sinapultide is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Pulmonary Surfactants. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.