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CHEBI ONTOLOGY - ANNOTATIONS

The Chemical Entities of Biological Interest (ChEBI) ontology is downloaded weekly from EMBL-EBI at http://www.ebi.ac.uk/chebi/. The data is made available under the Creative Commons License (CC BY 3.0, http://creativecommons.org/licenses/by/3.0/). For more information see: Degtyarenko et al. (2008) ChEBI: a database and ontology for chemical entities of biological interest. Nucleic Acids Res. 36, D344–D350.
Term:everolimus
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Accession:CHEBI:68478 term browser browse the term
Definition:A macrocyclic lactone that is rapamycin in which the hydroxy group attached to the cyclohexyl moiety has been converted into the corresponding 2-hydroxyethyl ether. It is an immunosuppressant and antineoplastic agent.
Synonyms:exact_synonym: (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-3-{(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl}-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone
 related_synonym: (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,35R)-1,18-dihydroxy-12-{(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl}-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0(4,9)]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone;   40-O-(2-hydroxyethyl)-rapamycin;   42-O-(2-Hydroxyethyl)rapamycin;   Afinitor;   Afinitor Disperz;   Certican;   Formula=C53H83NO14;   InChI=1S/C53H83NO14/c1-32-16-12-11-13-17-33(2)44(63-8)30-40-21-19-38(7)53(62,68-40)50(59)51(60)54-23-15-14-18-41(54)52(61)67-45(35(4)28-39-20-22-43(66-25-24-55)46(29-39)64-9)31-42(56)34(3)27-37(6)48(58)49(65-10)47(57)36(5)26-32/h11-13,16-17,27,32,34-36,38-41,43-46,48-49,55,58,62H,14-15,18-26,28-31H2,1-10H3/b13-11+,16-12+,33-17+,37-27+/t32-,34-,35-,36-,38-,39+,40+,41+,43-,44+,45+,46-,48-,49+,53-/m1/s1;   InChIKey=HKVAMNSJSFKALM-GKUWKFKPSA-N;   RAD 001;   RAD001;   SDZ-RAD;   SMILES=[H][C@]1(CC[C@@H](OCCO)[C@@H](C1)OC)C[C@@H](C)[C@]1([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](C[C@]2([H])CC[C@@H](C)[C@@](O)(O2)C(=O)C(=O)N2CCCC[C@@]2([H])C(=O)O1)OC;   Votubia;   Xience V;   Zortress;   everolimusum
 alt_id: MESH:D000068338
 xref: CAS:159351-69-6;   Chemspider:21106307;   DrugBank:DB01590;   Drug_Central:1118;   HMDB:HMDB0015529;   KEGG:D02714;   LINCS:LSM-43172
 xref_mesh: MESH:C107135
 xref: PMID:22363408;   PMID:22404500;   PMID:22461124;   PMID:22683823;   PMID:22967800;   PMID:22969095;   PMID:22983698;   PMID:22986894;   PMID:31478889;   PMID:33640871;   PMID:33986025;   PMID:33998365;   PMID:34018490;   PMID:34225066;   PMID:34242751;   PMID:34253597;   PMID:34299359;   PMID:34467233;   PMID:34491881;   PMID:34527569;   Patent:CN102138903;   Patent:RU2008143550;   Patent:WO2012066502;   Wikipedia:Everolimus


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everolimus term browser
Symbol Object Name Qualifiers Evidence Notes Source PubMed Reference(s) RGD Reference(s) Position
G Abcb11 ATP binding cassette subfamily B member 11 decreases activity ISO Everolimus results in decreased activity of ABCB11 protein CTD PMID:23956101 NCBI chr 3:54,016,854...54,112,797
Ensembl chr 3:54,017,127...54,112,730 		JBrowse link
G Abcb1a ATP binding cassette subfamily B member 1A affects stability
multiple interactions
affects response to substance		 ISO ABCB1A protein affects the stability of Everolimus
bis(4-nitrophenyl)phosphate inhibits the reaction [ABCB1A protein affects the stability of Everolimus]; Everolimus inhibits the reaction [ABCB1A protein affects the metabolism of irinotecan]
ABCB1 polymorphism affects the susceptibility to Everolimus		 CTD PMID:24727322 PMID:27169792 NCBI chr 4:25,357,467...25,529,941
Ensembl chr 4:25,158,362...25,442,709 		JBrowse link
G Abcb1b ATP-binding cassette, sub-family B member 1B affects stability
multiple interactions		 ISO ABCB1B protein affects the stability of Everolimus
bis(4-nitrophenyl)phosphate inhibits the reaction [ABCB1B protein affects the stability of Everolimus]; Everolimus inhibits the reaction [ABCB1B protein affects the metabolism of irinotecan]		 CTD PMID:24727322 NCBI chr 4:25,242,761...25,325,194
Ensembl chr 4:25,242,798...25,325,199 		JBrowse link
G Abcg2 ATP binding cassette subfamily G member 2 affects stability
multiple interactions		 ISO ABCG2 protein affects the stability of Everolimus
bis(4-nitrophenyl)phosphate inhibits the reaction [ABCG2 protein affects the stability of Everolimus]; Everolimus inhibits the reaction [ABCG2 protein affects the metabolism of irinotecan]		 CTD PMID:24727322 NCBI chr 4:87,676,241...87,802,757
Ensembl chr 4:87,745,319...87,802,409 		JBrowse link
G Akt1 AKT serine/threonine kinase 1 increases phosphorylation
decreases phosphorylation
multiple interactions		 ISO
EXP		 Everolimus results in increased phosphorylation of AKT1 protein
Everolimus results in decreased phosphorylation of AKT1 protein
Everolimus inhibits the reaction [Doxorubicin results in decreased phosphorylation of AKT1 protein]; MK 2206 inhibits the reaction [Everolimus inhibits the reaction [Doxorubicin results in decreased phosphorylation of AKT1 protein]]		 CTD PMID:16033851 PMID:22885370 PMID:23300809 PMID:28711525 PMID:37739323 NCBI chr 6:131,713,716...131,735,319
Ensembl chr 6:131,713,720...131,733,921 		JBrowse link
G Akt2 AKT serine/threonine kinase 2 increases phosphorylation
multiple interactions		 ISO
EXP		 Everolimus results in increased phosphorylation of AKT2 protein
Everolimus inhibits the reaction [Doxorubicin results in decreased phosphorylation of AKT2 protein]; MK 2206 inhibits the reaction [Everolimus inhibits the reaction [Doxorubicin results in decreased phosphorylation of AKT2 protein]]		 CTD PMID:37739323 NCBI chr 1:82,877,228...82,933,828
Ensembl chr 1:82,883,547...82,933,817 		JBrowse link
G Akt3 AKT serine/threonine kinase 3 multiple interactions
increases phosphorylation		 EXP
ISO		 Everolimus inhibits the reaction [Doxorubicin results in decreased phosphorylation of AKT3 protein]; MK 2206 inhibits the reaction [Everolimus inhibits the reaction [Doxorubicin results in decreased phosphorylation of AKT3 protein]]
Everolimus results in increased phosphorylation of AKT3 protein		 CTD PMID:37739323 NCBI chr13:88,943,708...89,225,831
Ensembl chr13:88,946,091...89,225,708 		JBrowse link
G Bax BCL2 associated X, apoptosis regulator multiple interactions EXP Everolimus inhibits the reaction [Doxorubicin results in increased expression of BAX protein] CTD PMID:37739323 NCBI chr 1:95,940,001...95,945,407
Ensembl chr 1:95,938,808...95,945,368 		JBrowse link
G Bcl2 BCL2, apoptosis regulator multiple interactions EXP Everolimus inhibits the reaction [Doxorubicin results in decreased expression of BCL2 protein] CTD PMID:37739323 NCBI chr13:22,689,783...22,853,920
Ensembl chr13:22,684,989...22,853,743
Ensembl chr13:22,684,989...22,853,743 		JBrowse link
G Birc5 baculoviral IAP repeat-containing 5 decreases expression
multiple interactions		 ISO Everolimus results in decreased expression of BIRC5 protein
Everolimus promotes the reaction [platycodin D results in decreased expression of BIRC5 protein]; navitoclax promotes the reaction [Everolimus results in decreased expression of BIRC5 protein]; platycodin D promotes the reaction [Everolimus results in decreased expression of BIRC5 protein]		 CTD PMID:21601561 PMID:28711525 PMID:28947240 NCBI chr10:103,072,530...103,081,382
Ensembl chr10:103,073,408...103,081,380 		JBrowse link
G Brd4 bromodomain containing 4 multiple interactions ISO [MYC protein results in decreased susceptibility to Everolimus] promotes the reaction [BRD4 protein binds to MYC gene] CTD PMID:25537515 NCBI chr 7:11,216,446...11,296,029
Ensembl chr 7:11,216,446...11,295,539 		JBrowse link
G Casp3 caspase 3 increases cleavage ISO Everolimus results in increased cleavage of CASP3 protein CTD PMID:15940265 NCBI chr16:45,662,910...45,681,171
Ensembl chr16:45,662,910...45,684,648 		JBrowse link
G Ccna2 cyclin A2 decreases expression ISO Everolimus results in decreased expression of CCNA2 protein CTD PMID:16856892 NCBI chr 2:119,427,239...119,433,645
Ensembl chr 2:119,426,089...119,433,577 		JBrowse link
G Ccnd1 cyclin D1 decreases expression
multiple interactions		 ISO Everolimus results in decreased expression of CCND1 protein
[letrozole co-treated with Everolimus] results in decreased expression of CCND1 protein		 CTD PMID:16033851 NCBI chr 1:200,089,002...200,098,524
Ensembl chr 1:200,089,002...200,098,602 		JBrowse link
G Ccnd2 cyclin D2 multiple interactions
decreases expression		 ISO [letrozole co-treated with Everolimus] results in decreased expression of CCND2 protein
Everolimus results in decreased expression of CCND2 protein		 CTD PMID:16033851 NCBI chr 4:159,966,883...159,989,261
Ensembl chr 4:159,962,363...159,989,495 		JBrowse link
G Ccnd3 cyclin D3 decreases expression ISO Everolimus results in decreased expression of CCND3 protein CTD PMID:16856892 NCBI chr 9:13,394,161...13,400,341
Ensembl chr 9:13,394,169...13,489,371 		JBrowse link
G Cdh1 cadherin 1 increases expression ISO Everolimus results in increased expression of CDH1 protein CTD PMID:28258630 NCBI chr19:34,492,371...34,561,775
Ensembl chr19:34,492,371...34,561,775 		JBrowse link
G Ces1d carboxylesterase 1D decreases activity ISO Everolimus results in decreased activity of CES1 protein CTD PMID:24727322 NCBI chr19:13,873,490...13,912,035
Ensembl chr19:13,796,623...13,912,035 		JBrowse link
G Ces2h carboxylesterase 2H decreases activity ISO Everolimus results in decreased activity of CES2 protein CTD PMID:24727322 NCBI chr19:32,974,242...32,988,842
Ensembl chr19:32,974,242...32,988,830 		JBrowse link
G Cycs cytochrome c, somatic multiple interactions EXP Everolimus inhibits the reaction [Doxorubicin results in increased expression of CYCS protein] CTD PMID:37739323 NCBI chr 4:79,651,894...79,653,994
Ensembl chr 4:79,651,378...79,654,054
Ensembl chr18:79,651,378...79,654,054 		JBrowse link
G Egfr epidermal growth factor receptor increases expression
multiple interactions		 ISO Everolimus results in increased expression of EGFR mRNA; Everolimus results in increased expression of EGFR protein
platycodin D inhibits the reaction [Everolimus results in increased expression of EGFR protein]		 CTD PMID:28711525 NCBI chr14:91,176,979...91,349,722
Ensembl chr14:91,177,067...91,344,382 		JBrowse link
G Eif4e eukaryotic translation initiation factor 4E increases phosphorylation
multiple interactions		 ISO Everolimus results in increased phosphorylation of EIF4E protein
Everolimus inhibits the reaction [Estradiol results in decreased phosphorylation of EIF4E protein]		 CTD PMID:16033851 NCBI chr 2:227,066,519...227,099,261
Ensembl chr 2:227,066,673...227,098,683 		JBrowse link
G Eif4ebp1 eukaryotic translation initiation factor 4E binding protein 1 multiple interactions
decreases phosphorylation		 ISO [letrozole co-treated with Everolimus] results in increased phosphorylation of and results in decreased activity of EIF4EBP1 protein; Everolimus inhibits the reaction [Estradiol results in increased phosphorylation of and results in decreased activity of EIF4EBP1 protein]; Everolimus promotes the reaction [platycodin D results in decreased phosphorylation of EIF4EBP1 protein]; Everolimus results in increased phosphorylation of and results in decreased activity of EIF4EBP1 protein; platycodin D promotes the reaction [Everolimus results in decreased phosphorylation of EIF4EBP1 protein] CTD PMID:16033851 PMID:16856892 PMID:16951235 PMID:21372221 PMID:28711525 NCBI chr16:64,792,595...64,805,984
Ensembl chr16:64,790,226...64,805,984 		JBrowse link
G Eif4g1 eukaryotic translation initiation factor 4 gamma 1 multiple interactions ISO Everolimus inhibits the reaction [Estradiol results in increased phosphorylation of EIF4G1 protein] CTD PMID:16033851 NCBI chr11:80,221,919...80,241,958
Ensembl chr11:80,221,919...80,241,941 		JBrowse link
G F3 coagulation factor III, tissue factor multiple interactions ISO Everolimus promotes the reaction [TNF protein results in increased expression of F3 protein] CTD PMID:19567381 NCBI chr 2:209,827,061...209,838,666
Ensembl chr 2:209,826,959...209,838,668 		JBrowse link
G Igf1r insulin-like growth factor 1 receptor multiple interactions
increases expression		 ISO platycodin D inhibits the reaction [Everolimus results in increased expression of IGF1R protein]
Everolimus results in increased expression of IGF1R mRNA; Everolimus results in increased expression of IGF1R protein		 CTD PMID:28711525 NCBI chr 1:121,549,831...121,838,548
Ensembl chr 1:121,550,743...121,831,777 		JBrowse link
G Itgam integrin subunit alpha M multiple interactions ISO Everolimus promotes the reaction [Tretinoin results in increased expression of ITGAM protein] CTD PMID:29743969 NCBI chr 1:182,659,047...182,709,501
Ensembl chr 1:182,659,000...182,709,503 		JBrowse link
G Map1lc3a microtubule-associated protein 1 light chain 3 alpha increases lipidation EXP Everolimus results in increased lipidation of MAP1LC3A protein CTD PMID:37739323 NCBI chr 3:143,783,024...143,784,670
Ensembl chr 3:143,783,024...143,784,670 		JBrowse link
G Map1lc3b microtubule-associated protein 1 light chain 3 beta multiple interactions ISO Everolimus promotes the reaction [N-((1R,2S)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl)octanamide results in increased expression of and results in increased lipidation of MAP1LC3B protein] CTD PMID:32397857 NCBI chr19:49,665,795...49,673,655
Ensembl chr19:49,665,791...49,677,690 		JBrowse link
G Mmp9 matrix metallopeptidase 9 multiple interactions ISO Everolimus inhibits the reaction [4-cresol results in increased expression of MMP9 protein] CTD PMID:30910523 NCBI chr 3:153,684,158...153,692,118
Ensembl chr 3:153,683,858...153,692,120 		JBrowse link
G Mtor mechanistic target of rapamycin kinase multiple interactions
decreases activity
decreases phosphorylation		 ISO
EXP		 [Everolimus co-treated with Y 27632] inhibits the reaction [4-cresol results in increased phosphorylation of MTOR protein]; [Letrozole co-treated with Everolimus] inhibits the reaction [Androstenedione affects the activity of MTOR protein]; Everolimus inhibits the reaction [4-cresol results in increased phosphorylation of MTOR protein]; Everolimus inhibits the reaction [Androstenedione affects the activity of MTOR protein]; Everolimus inhibits the reaction [Estradiol affects the activity of MTOR protein]; Everolimus inhibits the reaction [MTOR results in decreased susceptibility to Trabectedin]
Everolimus results in decreased activity of MTOR; Everolimus results in decreased activity of MTOR protein
Everolimus inhibits the reaction [rhodioloside inhibits the reaction [[cobaltous chloride co-treated with NGF protein] results in decreased phosphorylation of MTOR protein]]
Everolimus results in decreased phosphorylation of MTOR protein		 CTD PMID:16033851 PMID:20890178 PMID:21622721 PMID:24989011 PMID:30910523 More... NCBI chr 5:158,884,856...158,994,311
Ensembl chr 5:158,884,804...158,994,311 		JBrowse link
G Myc MYC proto-oncogene, bHLH transcription factor multiple interactions
increases expression
decreases response to substance		 ISO [MYC protein results in decreased susceptibility to Everolimus] promotes the reaction [BRD4 protein binds to MYC gene]
Everolimus results in increased expression of MYC protein		 CTD PMID:25537515 NCBI chr 7:93,593,705...93,598,633
Ensembl chr 7:93,593,705...93,598,630 		JBrowse link
G Ngf nerve growth factor multiple interactions EXP Everolimus inhibits the reaction [rhodioloside inhibits the reaction [[cobaltous chloride co-treated with NGF protein] results in decreased phosphorylation of MTOR protein]]; Everolimus inhibits the reaction [rhodioloside inhibits the reaction [[cobaltous chloride co-treated with NGF protein] results in decreased phosphorylation of RPS6KB1 protein]] CTD PMID:24989011 NCBI chr 2:189,901,058...189,954,452
Ensembl chr 2:189,901,058...189,954,452 		JBrowse link
G Nos3 nitric oxide synthase 3 multiple interactions
decreases expression		 ISO Aspirin inhibits the reaction [Everolimus results in decreased expression of NOS3 protein]; cilostazol inhibits the reaction [Everolimus results in decreased expression of NOS3 protein] CTD PMID:19520256 NCBI chr 4:10,793,834...10,814,170
Ensembl chr 4:10,793,834...10,814,166 		JBrowse link
G Nr1i3 nuclear receptor subfamily 1, group I, member 3 decreases activity ISO Everolimus results in decreased activity of NR1I3 protein CTD PMID:30203046 NCBI chr13:83,632,940...83,638,193
Ensembl chr13:83,632,899...83,637,906 		JBrowse link
G Parp1 poly (ADP-ribose) polymerase 1 multiple interactions ISO [navitoclax co-treated with Everolimus] results in increased cleavage of PARP1 protein CTD PMID:28947240 NCBI chr13:92,307,593...92,339,406
Ensembl chr13:92,307,586...92,339,404 		JBrowse link
G Ptgs2 prostaglandin-endoperoxide synthase 2 increases expression EXP Everolimus results in increased expression of PTGS2 mRNA; Everolimus results in increased expression of PTGS2 protein CTD PMID:15937522 NCBI chr13:62,163,936...62,172,193
Ensembl chr13:62,163,932...62,172,188 		JBrowse link
G Ptk2 protein tyrosine kinase 2 decreases expression ISO Everolimus results in decreased expression of PTK2 protein modified form CTD PMID:28258630 NCBI chr 7:105,126,725...105,331,848
Ensembl chr 7:105,126,728...105,331,783 		JBrowse link
G Rb1 RB transcriptional corepressor 1 multiple interactions
decreases phosphorylation		 ISO [letrozole co-treated with Everolimus] results in decreased phosphorylation of and affects the activity of RB1 protein; Everolimus results in decreased phosphorylation of and affects the activity of RB1 protein
Everolimus results in decreased phosphorylation of RB1 protein		 CTD PMID:16033851 PMID:16856892 NCBI chr15:48,371,295...48,502,473
Ensembl chr15:48,371,296...48,502,302 		JBrowse link
G Rhoa ras homolog family member A decreases expression
multiple interactions		 ISO Everolimus results in decreased expression of RHOA protein
[Everolimus co-treated with Y 27632] inhibits the reaction [4-cresol results in increased expression of RHOA protein]		 CTD PMID:28258630 PMID:30910523 NCBI chr 8:108,991,926...109,025,746
Ensembl chr 8:108,991,954...109,025,746 		JBrowse link
G Rps6 ribosomal protein S6 multiple interactions
decreases phosphorylation		 ISO [letrozole co-treated with Everolimus] results in decreased phosphorylation of RPS6 protein; Everolimus inhibits the reaction [Estradiol results in increased phosphorylation of RPS6 protein]
Everolimus results in decreased phosphorylation of RPS6 protein		 CTD PMID:16033851 PMID:21372221 PMID:22885370 PMID:23151917 PMID:23300809 More... NCBI chr 5:101,371,716...101,374,576
Ensembl chr 5:101,371,136...101,374,602
Ensembl chr 5:101,371,136...101,374,602 		JBrowse link
G Rps6kb1 ribosomal protein S6 kinase B1 multiple interactions EXP
ISO		 Everolimus inhibits the reaction [rhodioloside inhibits the reaction [[cobaltous chloride co-treated with NGF protein] results in decreased phosphorylation of RPS6KB1 protein]]
Everolimus inhibits the reaction [Estradiol results in increased phosphorylation of RPS6KB1 protein]; Everolimus inhibits the reaction [TNF protein results in increased phosphorylation of RPS6KB1 protein]		 CTD PMID:16033851 PMID:19567381 PMID:24989011 NCBI chr10:71,323,777...71,367,908
Ensembl chr10:71,323,777...71,367,908 		JBrowse link
G Sirt1 sirtuin 1 multiple interactions
decreases expression		 ISO Aspirin inhibits the reaction [Everolimus results in decreased expression of SIRT1 protein]; cilostazol inhibits the reaction [Everolimus results in decreased expression of SIRT1 protein] CTD PMID:19520256 NCBI chr20:25,307,225...25,329,273
Ensembl chr20:25,306,917...25,329,260 		JBrowse link
G Src SRC proto-oncogene, non-receptor tyrosine kinase decreases expression ISO Everolimus results in decreased expression of SRC protein modified form CTD PMID:28258630 NCBI chr 3:146,091,969...146,139,492
Ensembl chr 3:146,091,841...146,139,476 		JBrowse link
G Tnf tumor necrosis factor multiple interactions ISO Everolimus inhibits the reaction [TNF protein results in increased phosphorylation of RPS6KB1 protein]; Everolimus promotes the reaction [TNF protein results in increased expression of F3 protein] CTD PMID:19567381 NCBI chr20:3,622,011...3,624,629
Ensembl chr20:3,622,011...3,624,629 		JBrowse link
G Vim vimentin decreases expression ISO Everolimus results in decreased expression of VIM protein CTD PMID:28258630 NCBI chr17:76,668,701...76,677,186
Ensembl chr17:76,668,647...76,677,187 		JBrowse link
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Term Annotations click to browse term
  CHEBI ontology 19911
    role 19854
      biological role 19852
        immunomodulator 15081
          immunosuppressive agent 13924
            everolimus 46
Path 2
Term Annotations click to browse term
  CHEBI ontology 19911
    subatomic particle 19909
      composite particle 19909
        hadron 19880
          baryon 19880
            nucleon 19909
              atomic nucleus 19880
                atom 19909
                  main group element atom 19849
                    p-block element atom 19849
                      carbon group element atom 19766
                        carbon atom 19785
                          organic molecular entity 19785
                            heteroorganic entity 19541
                              organochalcogen compound 19301
                                organooxygen compound 19193
                                  carbon oxoacid 18681
                                    carboxylic acid 18678
                                      carboacyl group 17728
                                        univalent carboacyl group 17728
                                          carbamoyl group 17548
                                            carboxamide 17580
                                              lactam 8393
                                                macrolide lactam 827
                                                  sirolimus 529
                                                    everolimus 46
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