Uses
Cyclosporin H is a minor analogue of the cyclosporin family which is immunologically inactive as it does not bind to immunophilin. Cyclopsorin H is the most extensively investigated of the minor cyclosporin analogues and displays a range of activities. It is a potent inhibitor of tumour-promoting phorbol esters on mouse skin in vivo, and of calcium/calmodulin-dependent EF-2 phosphorylation in vitro, a potent and selective antagonist of formyl peptide receptor and inhibitor of formyl peptide-induced superoxide formation.
Uses
Cyclosporin H is a minor analogue of the cyclosporin family which is immunologically inactive as it does not bind to immunophilin. Cyclosporin H is the most extensively investigated of the minor cyclosporin analogues . It is a potent inhibitor of tumor-promoting phorbol esters on mouse skin in vivo, and of calcium/calmodulin-dependent EF-2 phosphorylation in vitro, a potent and selective antagonist of formyl peptide receptor and inhibitor of formyl peptide-induced superoxide formation.
Description
Cyclosporin H is a natural cyclic undecapeptide that selectively antagonizes the formyl peptide receptor at concentrations ranging from 0.1 to 10 μM.
1,2,3 Unlike cyclosporin A (Item No.
12088), cyclosporin H does not bind cyclophilin to evoke an immunosuppressant response.
4 Cyclosporin H has been reported to inhibit phorbol ester-mediated effects in mouse skin and block calcium/calmodulin-dependent EF-2 phosphorylation
in vitro.
5
Biochem/physiol Actions
Cyclosporin H is a selective inhibitor of formyl peptide receptor-1 (FPR-1) and formyl peptide-induced superoxide formation in neutrophils. Cyclosporin H does not bind cyclophilin or evoke an immunosuppressant response. Cyclosporin H has been reported to inhibit tumor promoting phorbol ester TPA/PMA in mouse skin cells and to inhibit calcium/calmodulin-dependent EF-2 phosphorylation.
References
[1]. wenzel-seifert k, seifert r. cyclosporin h is a potent and selective formyl peptide receptor antagonist. comparison with n-t-butoxycarbonyl-l-phenylalanyl-l-leucyl-l-phenylalanyl-l- leucyl-l-phenylalanine and cyclosporins a, b, c, d, and e. j immunol, 1993, 150(10): 4591-4599.
[2]. wenzel-seifert k, grünbaum l, seifert r. differential inhibition of human neutrophil activation by cyclosporins a, d, and h. cyclosporin h is a potent and effective inhibitor of formyl peptide-induced superoxide formation. j immunol, 1991, 147(6): 1940-1946.
[3]. de paulis a, ciccarelli a, de crescenzo g, et al. cyclosporin h is a potent and selective competitive antagonist of human basophil activation by n-formyl-methionyl-leucyl-phenylalanine. j allergy clin immunol, 1996, 98(1): 152-164.
[4]. kitagaki k, nagai h, hayashi s, et al. facilitation of apoptosis by cyclosporins a and h, but not fk506 in mouse bronchial eosinophils. eur j pharmacol, 1997, 337(2-3): 283-289.
