Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C43H69NO12 |
Molecular Weight | 792.0075 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 14 / 14 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@]1(CC[C@@H](O)[C@@H](C1)OC)\C=C(/C)[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@]4(O)O[C@@]([H])([C@H](C[C@H]4C)OC)[C@H](C[C@@H](C)C\C(C)=C\[C@@H](CC)C(=O)C[C@H](O)[C@H]2C)OC
InChI
InChIKey=ZDQSOHOQTUFQEM-NURRSENYSA-N
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
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/21833838Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/10794694 | https://www.ncbi.nlm.nih.gov/pubmed/23957229 | https://www.ncbi.nlm.nih.gov/pubmed/10197049 | https://www.ncbi.nlm.nih.gov/pubmed/26794830 | https://www.ncbi.nlm.nih.gov/pubmed/24628911
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21833838
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/10794694 | https://www.ncbi.nlm.nih.gov/pubmed/23957229 | https://www.ncbi.nlm.nih.gov/pubmed/10197049 | https://www.ncbi.nlm.nih.gov/pubmed/26794830 | https://www.ncbi.nlm.nih.gov/pubmed/24628911
Immunomycin (Ascomycin, FR-900520, FK520) is a macrocyclic lactone produced by S. hygroscopicus. It is well known as an antifungal and antibiotic agent. Immunomycin is an analog of FK506 and also contains a 23-membered ring. Both FK506 and Immunomycin bind to FKBP12 at the same binding site for hindering calcineurin. Thus, Immunomycin possesses immunosuppressive activity similar to that of FK506. It appears that Immunomycin inhibits the production of Th1 (interferon- and IL-2) and Th2 (IL-4 and IL-10) cytokines. Additionally, Immunomycin preferentially inhibits the activation of mast cells, an important cellular component of the atopic response. Immunomycin 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. Immunomycin is a member of the polyketide group of compounds. The polyketide synthase (PKS) enzyme is used to produce polyketides. The preparation of polyketide compounds has low product yield with traditional chemical methodology using wild-type cells. Reeves et al. provide a novel method of preparing a polyketide using a host cell with a recombinant DNA vector. The recombinant DNA vector contains nucleic acids that can encode the Immunomycin PKS enzyme. Immunomycin synthesized using this technology yields PKS at higher levels than that achieved by PKS in nature.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4050 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10794694 |
8.0 µM [IC50] | ||
Target ID: CHEMBL1902 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9599228 |
2.1 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Rapamycin-FKBP12 blocks proliferation, induces differentiation, and inhibits cdc2 kinase activity in a myogenic cell line. | 1993 Dec 5 |
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Tau phosphorylation in brain slices: pharmacological evidence for convergent effects of protein phosphatases on tau and mitogen-activated protein kinase. | 1995 Apr |
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Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells. | 1995 Mar |
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Nephrotoxicity studies of the immunosuppressants tacrolimus (FK506) and ascomycin in rat models. | 1998 Feb 6 |
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Potent immunosuppressive C32-O-arylethyl ether derivatives of ascomycin with reduced toxicity. | 1999 Jul 19 |
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Anticonvulsant effect of the calcineurin inhibitor ascomycin on seizures induced by picrotoxin microperfusion in the rat hippocampus. | 2006 Jul |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9570331
Rats were dosed intraperitoneally once a day for 14 consecutive days with Ascomycin (1.5, 5, 15, 50 mg/kg/day).
Route of Administration:
Intraperitoneal
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24628911
The cytotoxic effect of FK520 on S. cerevisiae control cells (AD1–8u-) and on cells over-expressing Cdr1 protein (AD-CDR1), Pdr5 protein (AD-PDR5), and Mdr1 protein (AD-MDR1) was determined by growth inhibition assay. Yeast cells (104) were seeded into 96-well plates in the absence and the presence of varying concentrations of FK520 (1–200 mkg/mL) and were grown for 48 h at 30 °C. Absorbance was measured using a microplate spectrophotometer at 600 nm. The percentage of growth inhibition was calculated considering the growth of cells without the inhibitor as 100% as (mean absorbance in test wells)/(mean absorbance in control wells) x 100.
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DTXSID80894126
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104987-12-4
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106410
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135635-46-0
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5282071
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Ascomycin
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29582
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SUBSTANCE RECORD