Ascomycin

Ascomycin

Ascomycin is a macrolide immunosuppressant that was first isolated from the bacteria Streptomyces hygroscopicus var. aspergillus. It is a derivative of the naturally occurring compound FK506 (tacrolimus), and is also known as immunomycin or FR-900520.

Chemistry

Ascomycin is a 23-membered polyketide macrolide with a molecular formula of C43H69NO12. It is structurally similar to tacrolimus, differing only by the presence of an ethyl group instead of an allyl group at the 31-position of the macrolide ring. This minor structural difference results in significant changes in the biological activity of ascomycin.

Pharmacology

Ascomycin acts by binding to the immunophilin FKBP12 (FK506 binding protein), creating a new complex. This complex then binds to and inhibits the enzyme calcineurin, which is involved in the activation of T cells of the immune system. By inhibiting calcineurin, ascomycin prevents the transcription of certain cytokines, particularly interleukin-2, thereby suppressing the immune response.

Clinical Use

Ascomycin and its derivatives have been investigated for use in a variety of conditions, including organ transplantation, autoimmune diseases, and atopic dermatitis. In the field of dermatology, a topical formulation of ascomycin (known as pimecrolimus) has been approved for the treatment of mild to moderate atopic dermatitis.

Side Effects

The side effects of ascomycin are similar to those of other calcineurin inhibitors and may include kidney damage, hypertension, hyperglycemia, and neurotoxicity. However, these side effects are less common with topical use.

See Also

• Macrolide
• Immunosuppressant
• FK506
• Calcineurin