Cyclosporin Analogue Set

BOC Sciences provides a diversity of metabolites fermented and separated from plants, bacteria, fungi, and other organisms. We have been committed to providing customers with high-quality cyclosporin and its analogues at the best price. In addition, we provide fermentation CDMO services to customize cyclosporin analogues to meet the needs of customers in the pharmaceutical and other industries.

What is Cyclosporine?

Cyclosporin is a non-ribosomal cyclic peptide composed of 11 normal and abnormal amino acids. It was first isolated and identified in 1971, and more than 30 structural analogues have been found successively. Cyclosporin A (CsA) is the first cyclosporin analogue approved by FDA as an anti-immune rejection drug, hydrophilic immunosuppressive active sites can be formed on the residues of amino acids 1, 2, 3 and 11. Initially isolated from the fungus Tolypocladium inflatum Gams, this compound gained widespread attention for its ability to modulate the immune system, making it an invaluable tool in various medical applications.

Cyclosporine Synthesis

CsA is produced through fungus fermentation processes. The molecule contains several unusual amino acids such as L-2-aminobutyric acid and D-alanine. In addition, the CsA molecule contains seven N-methylated peptide bonds. Biosynthesis of CsA is catalyzed by a specific polypeptide polyenzyme, Cyclosporin synthase. This enzyme catalyzes CsA synthesis from unmethylated precursor amino acids through a sulfur template mechanism. When these substrate amino acids bind to the enzyme in the form of thioesters, they are catalyzed by methyltransferases in Cyclosporin synthase for N-methylation reactions. The mechanism of Cyclosporin synthesis have been reported. It was proved that the SimG pathway in gene cluster was responsible for the synthesis of abnormal amino acid 2-butyl-4-methyl-threonine Bmt, and the racemase SimB was responsible for the conversion of L-alanine to D-alanine, and then the sequence addition and cycination of 11 substrates were mediated by SimA to produce CsA.

Fig. 1 Synthesis mechanism and biological function of Cyclosporin (Yang, 2018)

At the heart of BOC Sciences' offerings is our expertise in fermentation processes that are integral to cyclosporine synthesis. Our state-of-the-art facilities and experienced team ensure the production of high-quality cyclosporine through meticulous fermentation, providing pharmaceutical manufacturers with a reliable source of this critical compound.

Cyclosporine Mechanism of Action

Cyclosporine falls within the class of calcineurin inhibitors, a category that includes other critical drugs like tacrolimus. Unlike broad-spectrum immunosuppressants, cyclosporine primarily targets T-lymphocytes, a subset of white blood cells crucial for orchestrating immune responses. Cyclosporin can selectively act on the initial stage of T lymphocyte activation and inhibit the interleukin 2 produced after the activation of helper T cells. By blocking the activation of T-lymphocytes, cyclosporine prevents the release of inflammatory mediators, effectively suppressing the immune response.

This targeted approach is especially valuable in transplantation medicine, where the goal is to prevent the rejection of transplanted organs or tissues. Additionally, cyclosporine finds application in autoimmune diseases, where an overactive immune system mistakenly attacks healthy tissues.

Cyclosporine Toxicity

Cyclosporine is not without its potential side effects and toxicities. Potential toxicities include nephrotoxicity, neurotoxicity, and increased susceptibility to infections. BOC Sciences places a premium on quality assurance in our fermentation processes, recognizing the potential toxicity associated with cyclosporine. Rigorous monitoring and testing protocols are in place to ensure the highest purity of the compound, mitigating the risks of adverse effects. Our commitment to quality extends to every stage of the fermentation process, from raw materials to the final product.

What is Cyclosporine Used For?

The applications of cyclosporine are diverse, ranging from preventing organ rejection post-transplantation to managing autoimmune diseases. BOC Sciences, as a fermentation CDMO, takes pride in supporting pharmaceutical manufacturers across these applications.

• Organ Transplantation: Cyclosporine plays a pivotal role in preventing organ rejection following transplantation. By suppressing the immune system, it allows the recipient's body to accept the transplanted organ without mounting an immune response.
• Autoimmune Diseases: Cyclosporine is used to manage autoimmune disorders, including rheumatoid arthritis, psoriasis, and inflammatory bowel diseases. In these conditions, the immune system erroneously attacks the body's own tissues, and cyclosporine helps temper this hyperactive response.
• Ophthalmology: Modified cyclosporine formulations find application in ophthalmology, particularly in the treatment of certain eye conditions such as dry eye disease.

Reference

1. Yang, X., et al., Cyclosporine Biosynthesis in Tolypocladium inflatum Benefits Fungal Adaptation to the Environment., MBio, 2018, 9.