====== Rapamycin 1μM R00 exp29 ====== ==== Mechanism of Action ==== Allosteric mTORC1 inhibitor, forms ternary complex with FKBP12 and mTOR, attenuates protein synthesis and metabolism * **Class / Subclass 1:** Signal Transduction / Kinase Inhibitor * **Class / Subclass 2:** Proteostasis / mTOR inhibitor ==== Technical Notes ==== * **PubChem Name:** %%Sirolimus%% * **Synonyms:** Sirolimus; AY 22989 * **CAS #:** 53123-88-9 * **PubChem CID:** [[https://pubchem.ncbi.nlm.nih.gov/compound/5284616|5284616]] * **IUPAC:** %%(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone%% * **INCHI Name:** InChI=1S/C51H79NO13/c1-30-16-12-11-13-17-31(2)42(61-8)28-38-21-19-36(7)51(60,65-38)48(57)49(58)52-23-15-14-18-39(52)50(59)64-43(33(4)26-37-20-22-40(53)44(27-37)62-9)29-41(54)32(3)25-35(6)46(56)47(63-10)45(55)34(5)24-30/h11-13,16-17,25,30,32-34,36-40,42-44,46-47,53,56,60H,14-15,18-24,26-29H2,1-10H3/b13-11+,16-12+,31-17+,35-25+/t30-,32-,33-,34-,36-,37+,38+,39+,40-,42+,43+,44-,46-,47+,51-/m1/s1 * **INCHI Key:** QFJCIRLUMZQUOT-HPLJOQBZSA-N * **Molecular Weight:** 914.2 * **Canonical SMILES:** CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)O)C)C)O)OC)C)C)C)OC * **Isomeric SMILES:** C[C@@H]1CC[C@H]2C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CC[C@H]([C@@H](C4)OC)O)C)/C)O)OC)C)C)/C)OC * **Molecular Formula:** C51H79NO13 {{:chemogenomics:structures:chem-0016.svg?nolink}} * **Supplier Name:** LC Laboratories * **Catalog #:** R-5000 * **Lot #:** ASW-130 * **HRMS (ESI-TOF) m/z:** (M+Na)+ Calcd for C51H79NO13 936.54436; found 936.54366 * **Platform ID:** Rapamycin * **Min:** 29.4254; **Max:** 49.7567 {{:chemogenomics:dose_response:dr_273.png?nolink&500 |}} \\ \\ \\ \\ |< 300px 100px 200px >| ^ IC ^ Concentration (µM) ^ | IC10 |N/A | | IC20 |N/A | | IC30 |N/A | | IC40 |N/A | | IC50 |N/A | | IC60 |N/A | | IC70 |N/A | | IC80 |N/A | | IC90 |N/A | \\ ==== Screen Summary ==== * **Round**: 00 * **Dose**: 1µM * **Days of incubation**: 8 * **Doublings**: 5.2 * **Numbers of reads**: 10402895 ==== Screen Results ==== ^Sensitive/Resistant hits (FDR<0.05)^CRANKS^Score Plot^Top 30 Genes^Screen Similarity^Top 30 Sensitive GO terms^Top 30 Resistant GO terms^ |7/45|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Rapamycin_1uM_Round-0_exp29.txt|Scores]]|||||| {{:chemogenomics:cranks_plots:exp29.png?nolink}} ^Gene^CRANKS Score^FDR^ |[[:human_genes:U:UXS1|UXS1]]|-3.75|<0.01| |[[:human_genes:O:ORC3|ORC3]]|-3.44|<0.01| |[[:human_genes:A:ASB3|ASB3]]|-3.42|<0.01| |[[:human_genes:L:LMO2|LMO2]]|-3.00|<0.01| |[[:human_genes:L:LAMTOR4|LAMTOR4]]|-2.96|0.01| |[[:human_genes:S:SOX7|SOX7]]|-2.86|0.02| |[[:human_genes:D:DHX29|DHX29]]|-2.69|0.02| |[[:human_genes:M:MNS1|MNS1]]|-2.58|0.06| |[[:human_genes:R:RRAGA|RRAGA]]|-2.55|0.06| |[[:human_genes:C:COX7A2L|COX7A2L]]|-2.46|0.06| |[[:human_genes:G:GNA13|GNA13]]|-2.44|0.06| |[[:human_genes:M:MEF2C|MEF2C]]|-2.42|0.06| |[[:human_genes:X:XPOT|XPOT]]|-2.41|0.09| |[[:human_genes:E:ERG|ERG]]|-2.40|0.09| |[[:human_genes:G:GPR75-ASB3|GPR75-ASB3]]|-2.37|0.07| |[[:human_genes:T:TRIP12|TRIP12]]|-2.35|0.07| |[[:human_genes:X:XPO5|XPO5]]|-2.33|0.21| |[[:human_genes:D:DCAF15|DCAF15]]|-2.27|0.10| |[[:human_genes:P:PHF15|PHF15]]|-2.26|0.09| |[[:human_genes:C:CAMK2G|CAMK2G]]|-2.26|0.09| |[[:human_genes:F:FAF2|FAF2]]|-2.24|0.12| |[[:human_genes:I:ID3|ID3]]|-2.24|0.09| |[[:human_genes:D:DCAF5|DCAF5]]|-2.24|0.09| |[[:human_genes:S:SETD1B|SETD1B]]|-2.23|0.20| |[[:human_genes:E:EIF4E|EIF4E]]|-2.23|0.09| |[[:human_genes:A:ATF7IP|ATF7IP]]|-2.23|0.09| |[[:human_genes:Z:ZBTB7A|ZBTB7A]]|-2.22|0.09| |[[:human_genes:T:TRIM33|TRIM33]]|-2.20|0.09| |[[:human_genes:L:LAMTOR2|LAMTOR2]]|-2.19|0.09| |[[:human_genes:C:CALCB|CALCB]]|-2.19|0.15| |[[:human_genes:G:GID8|GID8]]|2.61|<0.01| |[[:human_genes:N:NME9|NME9]]|2.71|<0.01| |[[:human_genes:N:NCK1|NCK1]]|2.71|<0.01| |[[:human_genes:Z:ZFR|ZFR]]|2.72|0.09| |[[:human_genes:C:C19orf53|C19orf53]]|2.73|0.02| |[[:human_genes:R:RPS28|RPS28]]|2.73|0.16| |[[:human_genes:S:SLC25A1|SLC25A1]]|2.75|<0.01| |[[:human_genes:W:WEE1|WEE1]]|2.79|0.07| |[[:human_genes:S:SCAP|SCAP]]|2.81|<0.01| |[[:human_genes:B:BTK|BTK]]|2.84|<0.01| |[[:human_genes:C:CNOT7|CNOT7]]|2.96|<0.01| |[[:human_genes:P:PSMD11|PSMD11]]|3.01|<0.01| |[[:human_genes:A:ANP32E|ANP32E]]|3.02|<0.01| |[[:human_genes:G:GSK3B|GSK3B]]|3.04|<0.01| |[[:human_genes:M:MAEA|MAEA]]|3.07|<0.01| |[[:human_genes:W:WDR26|WDR26]]|3.08|<0.01| |[[:human_genes:P:PDS5B|PDS5B]]|3.16|<0.01| |[[:human_genes:P:PPP3CA|PPP3CA]]|3.20|<0.01| |[[:human_genes:O:OTUB1|OTUB1]]|3.34|<0.01| |[[:human_genes:C:CNOT2|CNOT2]]|3.46|<0.01| |[[:human_genes:K:KMT2E|KMT2E]]|3.59|<0.01| |[[:human_genes:C:CXorf56|CXorf56]]|3.68|<0.01| |[[:human_genes:F:FAM122A|FAM122A]]|3.85|<0.01| |[[:human_genes:M:MEMO1|MEMO1]]|3.88|<0.01| |[[:human_genes:C:CDK8|CDK8]]|4.00|<0.01| |[[:human_genes:P:PPP3R1|PPP3R1]]|4.37|<0.01| |[[:human_genes:U:UBE2H|UBE2H]]|4.64|<0.01| |[[:human_genes:C:CNOT8|CNOT8]]|5.66|<0.01| |[[:human_genes:Y:YPEL5|YPEL5]]|5.81|<0.01| |[[:human_genes:F:FKBP1A|FKBP1A]]|7.84|<0.01| ^Screen^Correlation^Plot^ |[[:results:exp306|Rapamycin 2μM R07 exp306]]|0.14|| |[[:results:exp308|Rapamycin 2μM plus FK-506 5μM R07 exp308]]|0.102|| |[[:results:exp307|Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307]]|0.079|| |[[:results:exp82|Torin1 0.08μM R02 exp82]]|0.055|| |[[:results:exp37|Wortmannin 0.5μM R00 exp37]]|0.051|| |[[:results:exp30|Rapamycin 10μM R00 exp30]]|0.185|| |[[:results:exp429|Rapamycin 0.001μM R08 exp429]]|0.164|| |[[:results:exp352|Dexamethasone 0.006 to 0.015μM on day4 R07 exp352]]|0.06|| |[[:results:exp351|Dexamethasone 0.006μM R07 exp351]]|0.059|| |[[:results:exp15|Cycloheximide 0.2μM R00 exp15]]|0.058|| |[[:results:exp70|INK128 0.2μM R02 exp70]]|0.057|| |[[:results:exp71|KU-0063794 3.8μM R02 exp71]]|0.054|| |[[:results:exp25|Oligomycin-A 2μM R00 exp25]]|0.054|| |[[:results:exp504|MK2206 4μM R08 exp504]]|0.052|| |[[:results:exp16|DABN 2μM R00 exp16]]|0.052|| |[[:results:exp13|Chloramphenicol 20μM R00 exp13]]|0.052|| {{:chemogenomics:comparison_plots:exp29_vs_exp306.png?nolink |}} {{:chemogenomics:comparison_plots:exp29_vs_exp308.png?nolink |}} {{:chemogenomics:comparison_plots:exp29_vs_exp307.png?nolink |}} {{:chemogenomics:comparison_plots:exp29_vs_exp82.png?nolink |}} {{:chemogenomics:comparison_plots:exp29_vs_exp37.png?nolink |}} {{:chemogenomics:comparison_plots:exp29_vs_exp30.png?nolink |}} {{:chemogenomics:comparison_plots:exp29_vs_exp429.png?nolink |}} {{:chemogenomics:comparison_plots:exp29_vs_exp352.png?nolink |}} {{:chemogenomics:comparison_plots:exp29_vs_exp351.png?nolink |}} {{:chemogenomics:comparison_plots:exp15_vs_exp29.png?nolink |}} {{:chemogenomics:comparison_plots:exp29_vs_exp70.png?nolink |}} {{:chemogenomics:comparison_plots:exp29_vs_exp71.png?nolink |}} {{:chemogenomics:comparison_plots:exp25_vs_exp29.png?nolink |}} {{:chemogenomics:comparison_plots:exp29_vs_exp504.png?nolink |}} {{:chemogenomics:comparison_plots:exp16_vs_exp29.png?nolink |}} {{:chemogenomics:comparison_plots:exp13_vs_exp29.png?nolink |}} ^GO Term^Fold Change^Genes^ |GTPase activator complex|177.65|LAMTOR4,RRAGA,LAMTOR2| |enzyme activator complex|118.44|LAMTOR4,RRAGA,LAMTOR2| ^GO Term^Fold Change^Genes^ |negative regulation of calcium ion import across plasma membrane|276.35|PPP3R1,PPP3CA| |GID complex|276.35|WDR26,MAEA| |CCR4-NOT core complex|221.08|CNOT2,CNOT7| |cellular response to interleukin-3|221.08|GSK3B,GSK3A| |negative regulation of glycogen biosynthetic process|221.08|GSK3B,GSK3A| |poly(A)-specific ribonuclease activity|138.18|CNOT8,CNOT2,CNOT7| |3-5-RNA exonuclease activity|47.37|CNOT8,CNOT2,CNOT7| |RNA exonuclease activity, producing 5-phosphomonoesters|43.63|CNOT8,CNOT2,CNOT7| |regulation of calcineurin-NFAT signaling cascade|43.63|PPP3R1,PPP3CA,GSK3B| |regulation of calcineurin-mediated signaling|42.52|PPP3R1,PPP3CA,GSK3B| |proteasome-mediated ubiquitin-dependent protein catabolic process|11.25|UBE2H,WDR26,MAEA,GSK3B,PSMD11,GID8,GSK3A| |proteasomal protein catabolic process|10.21|UBE2H,WDR26,MAEA,GSK3B,PSMD11,GID8,GSK3A| |proteolysis involved in protein catabolic process|7.60|UBE2H,WDR26,MAEA,GSK3B,PSMD11,CLPP,GID8,GSK3A| |ubiquitin-dependent protein catabolic process|7.59|UBE2H,WDR26,MAEA,GSK3B,PSMD11,GID8,GSK3A| |intracellular protein-containing complex|7.57|YPEL5,CNOT8,PPP3R1,CNOT2,PPP3CA,WDR26,MAEA,GSK3B,PSMD11,CNOT7,GID8,GSK3A| |modification-dependent protein catabolic process|7.44|UBE2H,WDR26,MAEA,GSK3B,PSMD11,GID8,GSK3A| |modification-dependent macromolecule catabolic process|7.29|UBE2H,WDR26,MAEA,GSK3B,PSMD11,GID8,GSK3A| |macromolecule catabolic process|7.20|CNOT8,UBE2H,CNOT2,WDR26,MAEA,GSK3B,PSMD11,CNOT7,BTK,CLPP,GID8,GSK3A| |protein catabolic process|7.17|UBE2H,WDR26,MAEA,GSK3B,PSMD11,BTK,CLPP,GID8,GSK3A|