Ascomycin

Ascomycin, also called Immunomycin, FR-900520, FK520, is an ethyl analog of tacrolimus (FK506) with strong immunosuppressant properties. It has been researched for the treatment of autoimmune diseases and skin diseases, and to prevent rejection after an organ transplant.

Ascomycin
Clinical data
Other names17-ethyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxy-cyclohexyl)-1-methyl-vinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone
ATC code
  • none
Identifiers
  • (3S,4R,5S,8R,9Z,12S,14S,15R,16S,18R,19R,26aS)-8-ethyl-5,19-dihydroxy-3-{(E)-2-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylvinyl}-14,16-dimethoxy-4,10,12,18-tetramethyl-4,5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-heptadecahydro-3H-15,19-epoxypyrido[2,1-c][1,4]oxazacyclotricosine-1,7,20,21(23H)-tetrone
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.108.430
Chemical and physical data
FormulaC43H69NO12
Molar mass792.020 g·mol−1
3D model (JSmol)
  • O=C3C(=O)N1CCCC[C@H]1C(=O)O[C@H](C(=C/[C@@H]2CC[C@@H](O)[C@H](OC)C2)/C)[C@H](C)[C@@H](O)CC(=O)[C@@H](/C=C(\C[C@@H](C[C@H](OC)[C@H]4O[C@]3(O)[C@H](C)C[C@@H]4OC)C)C)CC
  • InChI=1S/C43H69NO12/c1-10-30-18-24(2)17-25(3)19-36(53-8)39-37(54-9)21-27(5)43(51,56-39)40(48)41(49)44-16-12-11-13-31(44)42(50)55-38(28(6)33(46)23-34(30)47)26(4)20-29-14-15-32(45)35(22-29)52-7/h18,20,25,27-33,35-39,45-46,51H,10-17,19,21-23H2,1-9H3/b24-18+,26-20+/t25-,27+,28+,29-,30+,31-,32+,33-,35+,36-,37-,38+,39+,43+/m0/s1 Y
  • Key:ZDQSOHOQTUFQEM-NURRSENYSA-N Y
 NY (what is this?)  (verify)

Ascomycin acts by binding to immunophilins, especially macrophilin-12. It appears that Ascomycin inhibits the production of Th1 (interferon- and IL-2) and Th2 (IL-4 and IL-10) cytokines. Additionally, ascomycin preferentially inhibits the activation of mast cells, an important cellular component of the atopic response. Ascomycin produces a more selective immunomodulatory effect in that it inhibits the elicitation phase of allergic contact dermatitis but does not impair the primary immune response when administered systemically.

Ascomycin is produced by the fermentation of Streptomyces hygroscopicus.

In fiction

Ascomycin is also the name of a fictional "antiagathic" (anti-aging) drug in James Blish's future history Cities in Flight.

Tacrolimus, Pimecrolimus

References

    Further reading
    • Griffiths CE (April 2001). "Ascomycin: an advance in the management of atopic dermatitis". The British Journal of Dermatology. 144 (4): 679–681. doi:10.1046/j.1365-2133.2001.144004679.x. PMID 11298524.
    • Kawai M, Lane BC, Hsieh GC, Mollison KW, Carter GW, Luly JR (January 1993). "Structure-activity profiles of macrolactam immunosuppressant FK-506 analogues". FEBS Letters. 316 (2): 107–113. doi:10.1016/0014-5793(93)81196-7. PMID 7678400.
    • Zuberbier T, Chong SU, Grunow K, Guhl S, Welker P, Grassberger M, Henz BM (August 2001). "The ascomycin macrolactam pimecrolimus (Elidel, SDZ ASM 981) is a potent inhibitor of mediator release from human dermal mast cells and peripheral blood basophils". The Journal of Allergy and Clinical Immunology. 108 (2): 275–280. doi:10.1067/mai.2001.116865. PMID 11496246.
    • Mollison KW, Fey TA, Krause RA, Thomas VA, Mehta AP, Luly JR (June 1993). "Comparison of FK-506, rapamycin, ascomycin, and cyclosporine in mouse models of host-versus-graft disease and heterotopic heart transplantation". Annals of the New York Academy of Sciences. 685: 55–57. doi:10.1111/j.1749-6632.1993.tb35851.x. PMID 7689812.
    • Paul C, Graeber M, Stuetz A (January 2000). "Ascomycins: promising agents for the treatment of inflammatory skin diseases". Expert Opinion on Investigational Drugs. 9 (1): 69–77. doi:10.1517/13543784.9.1.69. PMID 11060661.
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