sirolimus
CHEBI:9168 EXACT SEEDED antibacterialcytotoxicenzyme inhibitor
A macrolide lactam isolated from Streptomyces hygroscopicus consisting of a 29-membered ring containing 4 trans double bonds, three of which are conjugated. It is an antibiotic, immunosupressive and antineoplastic agent.
Structure
| Standard InChIKey | QFJCIRLUMZQUOT-HPLJOQBZSA-N |
|---|---|
| SMILES | [H][C@@]12CC[C@@H](C)[C@@](O)(O1)C(=O)C(=O)N1CCCC[C@@]1([H])C(=O)O[C@@]([H])(CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C2)OC)[C@H](C)C[C@@H]1CC[C@@H](O)[C@@H](C1)OC |
| Stereochemistry | fully defined |
| Cross-references | npatlas:NPA0414, pubchem:5284616 |
Filing pathway
Polyketides — computed by NPClassifier npclassifier.gnps2.org@2026-09-07, which is why it is pinned rather than recomputed. The gene cluster's asserted class is nrps, pks, from MIBiG.
Producer organisms 1
A claim that this taxon makes the compound. The basis says what the evidence addressed — a knockout and a database assertion are not the same claim.
| Taxon | Basis | Cluster | Evidence |
|---|---|---|---|
| Streptomyces rapamycinicus NRRL 5491 NCBITaxon:1343740 |
SOURCE_ASSERTION | mibig:BGC0001040 | PMID:7644502 |
Occurrences 25
Somebody found the compound in this organism and cited it. That is not a claim that the organism makes it, and nothing here promotes one to the other.
| Taxon | Source | Reference |
|---|---|---|
| Purpureocillium NCBITaxon:1052105 |
LOTUS | DOI:10.1021/ACS.JNATPROD.0C00404 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1007/BF01573954 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1007/S00253-011-3348-6 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1007/S00449-013-1051-Y |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1016/0378-1119(95)00799-7 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1016/B978-0-12-404634-4.00017-6 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1016/J.JBIOSC.2013.03.011 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1016/S0006-291X(03)01231-2 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1016/S0378-1119(97)00450-2 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1038/SJ.JIM.2900434 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1074/JBC.RA118.005314 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1099/13500872-142-10-2815 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1099/13500872-145-8-1989 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1099/MIC.0.28194-0 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1111/J.1432-1033.1997.00526.X |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.1128/GENOMEA.00616-14 |
| Streptomyces rapamycinicus NCBITaxon:1226757 |
LOTUS | DOI:10.4014/JMB.1403.03024 |
| Streptomyces hygroscopicus NCBITaxon:1912 |
LOTUS | DOI:10.1007/BF01573954 |
| Streptomyces hygroscopicus NCBITaxon:1912 |
LOTUS | DOI:10.1007/S00253-011-3348-6 |
| Streptomyces hygroscopicus NCBITaxon:1912 |
LOTUS | DOI:10.1007/S00449-013-1051-Y |
| Streptomyces hygroscopicus NCBITaxon:1912 |
LOTUS | DOI:10.1016/0378-1119(95)00799-7 |
| Streptomyces hygroscopicus NCBITaxon:1912 |
LOTUS | DOI:10.1016/B978-0-12-404634-4.00017-6 |
| Streptomyces hygroscopicus NCBITaxon:1912 |
LOTUS | DOI:10.1016/J.JBIOSC.2013.03.011 |
| Streptomyces hygroscopicus NCBITaxon:1912 |
LOTUS | DOI:10.1016/S0006-291X(03)01231-2 |
| Streptomyces hygroscopicus NCBITaxon:1912 |
LOTUS | DOI:10.1016/S0378-1119(97)00450-2 |
Biosynthetic gene clusters 1
| Accession | Host | Locus evidence | Genome |
|---|---|---|---|
| mibig:BGC0001040 | Streptomyces rapamycinicus NRRL 5491 NCBITaxon:1343740 |
CLUSTER_UNSTATED | genbank:X86780.1 |
A locus claim and a taxon claim are different questions. Heterologous expression settles the first and leaves the second where the isolation report left it.
Causal graph — bioactivity 4 nodes, 4 edges
Sirolimus binds human FKBP12 and the FKBP12-sirolimus complex binds the human mTOR FKBP12-rapamycin-binding domain.
| Subject | Predicate | Object | Evidence |
|---|---|---|---|
| sirolimus | binds | human FKBP12 | DOI:10.1016/1074-5521(95)90264-3 |
| sirolimus | forms | human FKBP12-sirolimus complex | DOI:10.1016/1074-5521(95)90264-3 |
| human FKBP12 | forms | human FKBP12-sirolimus complex | DOI:10.1126/science.273.5272.239 |
| human FKBP12-sirolimus complex | binds | human mTOR FRB domain | DOI:10.1126/science.273.5272.239 |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Bioactivities 25
| Assay | Result | Reference |
|---|---|---|
| A quantitative high throughput screen for small molecules that induce DNA re-replication in MCF 10a normal breast cells. | 33.4983 uM | pubchem.aid:624296 |
| A quantitative high throughput screen for small molecules that induce DNA re-replication in SW480 colon adenocarcinoma cells. | 33.4983 uM | pubchem.aid:624297 |
| Experimentally measured binding affinity data (Kd) for protein-ligand complexes derived from PDB | KD 0.0002 uM | pubchem.aid:977611 |
| Experimentally measured binding affinity data (Ki) for protein-ligand complexes derived from PDB | KI 0.0009 uM | pubchem.aid:977610 |
| FKBP12 Assay from Article 10.1016/1074-5521(95)90264-3: "Structure-activity studies of rapamycin analogs: evidence that the C-7 methoxy group is part of the effector domain and positioned at the FKBP12-FRAP interface." | KI 0.001 uM | PMID:9383449 |
| Inhibitors of USP1/UAF1: Pilot qHTS | 35.4813 uM | pubchem.aid:504865 |
| Primary qHTS for delayed death inhibitors of the malarial parasite plastid, 48 hour incubation | 1.5101 uM | pubchem.aid:504832 |
| Primary qHTS for delayed death inhibitors of the malarial parasite plastid, 96 hour incubation | 1.5101 uM | pubchem.aid:504834 |
| S16 Schwann cell viability assay (CellTiter-Glo assay) | 0.0256 uM | pubchem.aid:624031 |
| SPR Assay to Determine Binding Affinity to FKBP12 from US Patent US11603377: "MTORC1 modulators and uses thereof" | KD 0.0003 uM | pubchem.aid:1919337 |
| SPR Assay to Determine Binding Affinity to FKBP51 from US Patent US11603377: "MTORC1 modulators and uses thereof" | KD 0.01 uM | pubchem.aid:1919338 |
| VP16 counterscreen qHTS for inhibitors of ROR gamma transcriptional activity | 31.6228 uM | pubchem.aid:2546 |
| qHTS for Inhibitors of TGF-b | 12.5893 uM | pubchem.aid:588855 |
| qHTS for Inhibitors of TGF-b: Cytotox Counterscreen | 35.4813 uM | pubchem.aid:588856 |
| qHTS for Inhibitors of human tyrosyl-DNA phosphodiesterase 1 (TDP1): qHTS in cells in absence of CPT | 8.9125 uM | pubchem.aid:686978 |
| qHTS for Inhibitors of human tyrosyl-DNA phosphodiesterase 1 (TDP1): qHTS in cells in presence of CPT | 4.4668 uM | pubchem.aid:686979 |
| qHTS for Stage-Specific Inhibitors of Vaccinia Orthopoxvirus: Venus Reporter Primary qHTS | 10 uM | pubchem.aid:720580 |
| qHTS for Stage-Specific Inhibitors of Vaccinia Orthopoxvirus: mCherry Reporter Primary qHTS | 8.9125 uM | pubchem.aid:720579 |
| qHTS for inhibitors of ROR gamma transcriptional activity | 35.4813 uM | pubchem.aid:2551 |
| qHTS of alpha-syn Inhibitors | 3.9811 uM | pubchem.aid:652106 |
| DSSTox (FDAMDD) FDA Maximum (Recommended) Daily Dose Database | ACTIVE | pubchem.aid:1195 |
| Experimentally measured binding affinity data derived from PDB | ACTIVE | pubchem.aid:1811 |
| Experimentally measured binding affinity data derived from PDB | ACTIVE | pubchem.aid:1811 |
| Expression of GFP-tagged protein in TOR C1 bypass strains and wild type Saccharomyces cerevisiae | ACTIVE | pubchem.aid:504479 |
| Expression of GFP-tagged protein in TOR C1 bypass strains and wild type Saccharomyces cerevisiae | ACTIVE | pubchem.aid:504479 |
Elsewhere in the fleet
- AntibioticMech — CHEBI:9168 (same structure, same inchikey)
Open questions 1
name-disagreement — ChEBI calls this structure 'sirolimus' and MIBiG calls it 'rapamycin'. They share a Standard InChIKey, so if the names denote different compounds then one upstream record has the wrong structure. Check which.
Provenance
| Source concept | Source | Version |
|---|---|---|
| BGC0001040 | MIBIG | 5 |
| CHEBI:9168 | CHEBI | 3-star |
This page is generated from data/natural_products/polyketides/sirolimus.yaml, which is generated from the committed inventories. Neither is edited by hand.