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.[1]

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
IUPAC name
  • (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)
SMILES
  • 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
  • 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.[2]

Ascomycin is produced by the fermentation of certain strains of Streptomyces hygroscopicus.[3]

In fiction

Ascomycin is also the name of a fictional "antiagathic" (anti-aging) drug in James Blish's future history Cities in Flight.[4]

Tacrolimus, Pimecrolimus

References
  1. Andexer, Jennifer; Kendrew, Steven; Nur-e-Alam, Mohammad; Wilkinson, Barrie (March 7, 2011). "Biosynthesis of the immunosuppressants FK506, FK520, and rapamycin involves a previously undescribed family of enzymes acting on chorismate". PNAS. 108 (12): 4776–4781. doi:10.1073/pnas.1015773108. Retrieved 15 June 2022.
  2. Paul, Carle; Graeber, Michael; Stuetz, Anton (23 Feb 2005). "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. Retrieved 15 June 2022.
  3. Yu, Zhitou; Lv, Huihui; Wu, Yuanjie; Chen, Shaoxin (12 November 2019). "Enhancement of FK520 production in Streptomyces hygroscopicus by combining traditional mutagenesis with metabolic engineering". Applied genetics and molecular biotechnology. 103: 9593–9606. doi:10.1007/s00253-019-10192-8. Retrieved 15 June 2022.
  4. "Anti-agathic drugs". Technovelgy.com. Retrieved 15 June 2022.

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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