Ascomycin

Ascomycin
Clinical data
Other names	17-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	104987-12-4 ;
PubChem CID	5282071;
ChemSpider	4445297 ;
UNII	AUF4U5NSJK;
ChEBI	CHEBI:29582 ;
ChEMBL	ChEMBL8597 ;
CompTox Dashboard (EPA)	DTXSID80894126 ;
ECHA InfoCard	100.108.430
Chemical and physical data
Formula	C43H69NO12
Molar mass	792.020 g·mol−1
3D model (JSmol)	Interactive image;
	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 ; Key:ZDQSOHOQTUFQEM-NURRSENYSA-N ;
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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 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]

^ Andexer JN, Kendrew SG, Nur-e-Alam M, Lazos O, Foster TA, Zimmermann AS, et al. (March 2011). "Biosynthesis of the immunosuppressants FK506, FK520, and rapamycin involves a previously undescribed family of enzymes acting on chorismate". Proceedings of the National Academy of Sciences of the United States of America. 108 (12): 4776–4781. doi:10.1073/pnas.1015773108. PMC 3064383. PMID 21383123.
^ 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. S2CID 19730971.
^ Yu Z, Lv H, Wu Y, Wei T, Yang S, Ju D, Chen S (December 2019). "Enhancement of FK520 production in Streptomyces hygroscopicus by combining traditional mutagenesis with metabolic engineering". Applied Microbiology and Biotechnology. 103 (23–24): 9593–9606. doi:10.1007/s00253-019-10192-8. PMID 31713669. S2CID 207955563.

[1] Andexer JN, Kendrew SG, Nur-e-Alam M, Lazos O, Foster TA, Zimmermann AS, et al. (March 2011). "Biosynthesis of the immunosuppressants FK506, FK520, and rapamycin involves a previously undescribed family of enzymes acting on chorismate". Proceedings of the National Academy of Sciences of the United States of America. 108 (12): 4776–4781. doi:10.1073/pnas.1015773108. PMC 3064383. PMID 21383123.

[2] 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. S2CID 19730971.

[3] Yu Z, Lv H, Wu Y, Wei T, Yang S, Ju D, Chen S (December 2019). "Enhancement of FK520 production in Streptomyces hygroscopicus by combining traditional mutagenesis with metabolic engineering". Applied Microbiology and Biotechnology. 103 (23–24): 9593–9606. doi:10.1007/s00253-019-10192-8. PMID 31713669. S2CID 207955563.

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