REVIEW Ascomycin is an ethyl analog of tacrolimus (FK506) with strong immunosuppressant properties. IC50 Value: 0.55 nM. Target: in vitro: When we used either CD4+CD8+ thymocytes or peripheral T cells activated by phorbol ester and ionomycin, the cell surface induction of CD5 was also partially blocked by CsA, FK-520 and rapamycin. Ascomycinalso had a 3-fold lower immunosuppressive potency in a popliteal lymph node hyperplasia assay, resulting in an equivalent therapeutic index consistent with a common mechanistic dependence on calcineurin inhibition. in vivo: In 14-day studies, nephrotoxicity was not induced by continuous i.p. infusion of ascomycin at 10 mg/kg/day or daily oral administration (up to 50 mg/kg/day) in rats on a normal diet, nor by continuous i.v. infusion (up to 6 mg/kg/day) in rats on a low salt diet to enhance susceptibility.
REFERENCES
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Mollison KW, Fey TA, Krause RA, Nephrotoxicity studies of the immunosuppressants tacrolimus (FK506) and ascomycin in rat models. Toxicology. 1998 Feb 6;125(2-3):169-81.
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Teutsch M, Higer M, Wang D, Induction of CD5 on B and T cells is suppressed by cyclosporin A, FK-520 and rapamycin. Int Immunol. 1995 Mar;7(3):381-92.
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Hatanaka H, Kino T, Miyata S, FR-900520 and FR-900523, novel immunosuppressants isolated from a Streptomyces. II. Fermentation, isolation and physico-chemical and biological characteristics. J Antibiot (Tokyo). 1988 Nov;41(11):1592-601.
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