Pimecrolimus

Pimecrolimus is an immunophilin ligand, which binds specifically to the cytosolic receptor, immunophilin macrophilin-12.Target: OthersPimecrolimus blocks T-lymphocyte activation pathway by inhibiting calcineurin function [1]. Pimecrolimus prevents the release of cytokines and pro-inflammatory mediators from mast cells. Pimecrolimus binds to macrophilin-12, the pimecrolimusmacrophilin complex then binds to the cytosolic enzyme calcineurin phosphatase. The pimecrolimus-macrophilin complex prevents the dephosphorylation of the cytoplasmic component of the nuclear factor of activated T cells by inhibiting the action of calcineurin. Pimecrolimus inhibits not only the transcription and synthesis of cytokines from mast cells, but also the release of preformed mediators serotonin and β-hexosaminidase by the inhibition of Fcε-RI-mediated degranulation and secretion. Pimecrolimus treatment causes a strong down-regulation of the expression of mRNA for genes associated with the macrolactam target pathway and inflammation [2].Pimecrolimus is found to be as effective as cyclosporine A following oral ingestion and slightly superior after subcutaneous administration in mice. Pimecrolimus contrasts cyclosporine A and tacrolimus by inhibiting ongoing secondary inflammatory response, but not impairing the primary immune response in allergic contact dermatitis in mice. [2] Pimecrolimus is as effective as the high-potency corticosteroid clobetasol-17-propionate in a pig model of allergic contact dermatitis (ACD). Pimecrolimus also effectively reduces skin inflammation and pruritus in hypomagnesemic hairless rats, a model that mimics acute signs of atopic dermatitis [3].

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

[1]. Nghiem, P., G. Pearson, and R.G. Langley, Tacrolimus and pimecrolimus: from clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J Am Acad Dermatol, 2002. 46(2): p. 228-41.

[2]. Gupta, A.K. and M. Chow, Pimecrolimus: a review. J Eur Acad Dermatol Venereol, 2003. 17(5): p. 493-503.

[3]. Stuetz, A., M. Grassberger, and J.G. Meingassner, Pimecrolimus (Elidel, SDZ ASM 981)--preclinical pharmacologic profile and skin selectivity. Semin Cutan Med Surg, 2001. 20(4): p. 233-41.

Captisol | Cyclosporin A | H2DCFDA | 0MPTP hydrochloride | GW4869 | Etomoxir | TD139 | Mitoquinone mesylate | GSK2795039 | JC-1 | BAPTA-AM | AP 20187 | Setanaxib (GKT137831) | D-Luciferin | Crotaline