====== Rapamycin 10μM R00 exp30 ======
==== 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 |}}
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^ 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 |
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==== Screen Summary ====
* **Round**: 00
* **Dose**: 10µM
* **Days of incubation**: 8
* **Doublings**: 3.5
* **Numbers of reads**: 10555392
==== 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^
|20/68|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Rapamycin_10uM_Round-0_exp30.txt|Scores]]||||||
{{:chemogenomics:cranks_plots:exp30.png?nolink}}
^Gene^CRANKS Score^FDR^
|[[:human_genes:A:ABCC1|ABCC1]]|-7.22|<0.01|
|[[:human_genes:T:TMEM30A|TMEM30A]]|-4.05|<0.01|
|[[:human_genes:U:UXS1|UXS1]]|-3.76|<0.01|
|[[:human_genes:S:SENP1|SENP1]]|-3.49|<0.01|
|[[:human_genes:G:GPR107|GPR107]]|-2.97|<0.01|
|[[:human_genes:Z:ZBTB10|ZBTB10]]|-2.82|0.02|
|[[:human_genes:M:MEF2A|MEF2A]]|-2.74|0.02|
|[[:human_genes:D:DSCAM|DSCAM]]|-2.74|0.01|
|[[:human_genes:T:TAF5L|TAF5L]]|-2.70|0.02|
|[[:human_genes:R:RHOA|RHOA]]|-2.67|0.02|
|[[:human_genes:S:SEC31A|SEC31A]]|-2.64|0.02|
|[[:human_genes:M:MEF2C|MEF2C]]|-2.63|0.02|
|[[:human_genes:D:DERL2|DERL2]]|-2.58|0.03|
|[[:human_genes:S:SPAG7|SPAG7]]|-2.57|0.02|
|[[:human_genes:T:TRIP12|TRIP12]]|-2.56|0.02|
|[[:human_genes:T:TCF4|TCF4]]|-2.56|0.02|
|[[:human_genes:L:LAMTOR4|LAMTOR4]]|-2.53|0.04|
|[[:human_genes:X:XPO5|XPO5]]|-2.46|0.13|
|[[:human_genes:I:ID3|ID3]]|-2.44|0.03|
|[[:human_genes:E:EIF5B|EIF5B]]|-2.44|0.13|
|[[:human_genes:C:CAMKV|CAMKV]]|-2.41|0.07|
|[[:human_genes:A:ATXN2L|ATXN2L]]|-2.39|0.07|
|[[:human_genes:A:ASB3|ASB3]]|-2.39|0.04|
|[[:human_genes:A:ATP8B2|ATP8B2]]|-2.37|0.11|
|[[:human_genes:S:SCYL1|SCYL1]]|-2.36|0.08|
|[[:human_genes:T:TIPRL|TIPRL]]|-2.34|0.05|
|[[:human_genes:E:ERG|ERG]]|-2.31|0.09|
|[[:human_genes:T:TK1|TK1]]|-2.31|0.06|
|[[:human_genes:A:ASUN|ASUN]]|-2.30|0.09|
|[[:human_genes:V:VPS51|VPS51]]|-2.27|0.10|
|[[:human_genes:N:NANS|NANS]]|2.77|<0.01|
|[[:human_genes:A:ARID4A|ARID4A]]|2.80|<0.01|
|[[:human_genes:C:CDC5L|CDC5L]]|2.88|<0.01|
|[[:human_genes:N:NDUFB8|NDUFB8]]|2.89|<0.01|
|[[:human_genes:N:NKTR|NKTR]]|2.89|0.02|
|[[:human_genes:Z:ZBTB18|ZBTB18]]|2.96|<0.01|
|[[:human_genes:K:KAT7|KAT7]]|2.96|<0.01|
|[[:human_genes:Z:ZFAND3|ZFAND3]]|3.01|<0.01|
|[[:human_genes:R:RBM26|RBM26]]|3.01|<0.01|
|[[:human_genes:M:MAEA|MAEA]]|3.02|<0.01|
|[[:human_genes:D:DAZAP1|DAZAP1]]|3.03|<0.01|
|[[:human_genes:S:SIRT6|SIRT6]]|3.08|<0.01|
|[[:human_genes:I:ITPR1|ITPR1]]|3.10|<0.01|
|[[:human_genes:P:PLCG2|PLCG2]]|3.13|<0.01|
|[[:human_genes:G:GID8|GID8]]|3.15|<0.01|
|[[:human_genes:C:CXorf56|CXorf56]]|3.48|<0.01|
|[[:human_genes:N:NFATC3|NFATC3]]|3.52|<0.01|
|[[:human_genes:C:CNOT2|CNOT2]]|3.68|<0.01|
|[[:human_genes:B:BTK|BTK]]|3.69|<0.01|
|[[:human_genes:C:CDK8|CDK8]]|3.81|<0.01|
|[[:human_genes:P:PPP3CA|PPP3CA]]|3.87|<0.01|
|[[:human_genes:F:FAM122A|FAM122A]]|4.29|<0.01|
|[[:human_genes:C:CNOT8|CNOT8]]|4.33|<0.01|
|[[:human_genes:A:ARID4B|ARID4B]]|4.36|<0.01|
|[[:human_genes:W:WDR26|WDR26]]|4.43|<0.01|
|[[:human_genes:M:MEMO1|MEMO1]]|4.68|<0.01|
|[[:human_genes:U:UBE2H|UBE2H]]|5.73|<0.01|
|[[:human_genes:P:PPP3R1|PPP3R1]]|5.80|<0.01|
|[[:human_genes:Y:YPEL5|YPEL5]]|6.73|<0.01|
|[[:human_genes:F:FKBP1A|FKBP1A]]|8.08|<0.01|
^Screen^Correlation^Plot^
|[[:results:exp29|Rapamycin 1μM R00 exp29]]|0.185||
|[[:results:exp306|Rapamycin 2μM R07 exp306]]|0.142||
|[[:results:exp307|Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307]]|0.1||
|[[:results:exp308|Rapamycin 2μM plus FK-506 5μM R07 exp308]]|0.089||
|[[:results:exp82|Torin1 0.08μM R02 exp82]]|0.056||
|[[:results:exp407|Thapsigargin 0.005μM R07 exp407]]|0.054||
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|0.054||
|[[:results:exp429|Rapamycin 0.001μM R08 exp429]]|0.148||
|[[:results:exp229|Dimethyloxaloylglycine 100μM R05 exp229]]|0.064||
|[[:results:exp488|Hippuristanol 0.12μM R08 exp488]]|0.063||
|[[:results:exp25|Oligomycin-A 2μM R00 exp25]]|0.062||
|[[:results:exp70|INK128 0.2μM R02 exp70]]|0.058||
|[[:results:exp504|MK2206 4μM R08 exp504]]|0.057||
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|0.057||
|[[:results:exp233|EPZ-5676 30μM R05 exp233]]|0.057||
|[[:results:exp498|Lead acetate 2000μM R08 exp498 no dilution day6]]|0.056||
|[[:results:exp234|Ethanol 0.01 R05 exp234]]|0.056||
|[[:results:exp216|Erlotinib 10μM R05 exp216]]|0.055||
|[[:results:exp485|GSK626616 14μM R08 exp485]]|0.054||
|[[:results:exp269|Bisphenol A 100μM R06 exp269]]|0.054||
|[[:results:exp317|Geldanamycin 0.015 to 0.05μM on day4 R07 exp317]]|0.054||
|[[:results:exp351|Dexamethasone 0.006μM R07 exp351]]|0.054||
|[[:results:exp489|Hippuristanol 0.12μM R08 exp489 no dilution day6]]|0.054||
|[[:results:exp449|Arsenic trioxide 60μM R08 exp449]]|0.051||
|[[:results:exp222|Betulinic acid 10 to 15μM on day4 R05 exp222]]|0.051||
{{:chemogenomics:comparison_plots:exp29_vs_exp30.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp306.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp307.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp308.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp82.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp407.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp535.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp429.png?nolink |}}
{{:chemogenomics:comparison_plots:exp229_vs_exp30.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp488.png?nolink |}}
{{:chemogenomics:comparison_plots:exp25_vs_exp30.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp70.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp504.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp497.png?nolink |}}
{{:chemogenomics:comparison_plots:exp233_vs_exp30.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp498.png?nolink |}}
{{:chemogenomics:comparison_plots:exp234_vs_exp30.png?nolink |}}
{{:chemogenomics:comparison_plots:exp216_vs_exp30.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp485.png?nolink |}}
{{:chemogenomics:comparison_plots:exp269_vs_exp30.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp317.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp351.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp489.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp449.png?nolink |}}
{{:chemogenomics:comparison_plots:exp222_vs_exp30.png?nolink |}}
No GO term hits below threshold. (FDR <0.05)
^GO Term^Fold Change^Genes^
|establishment of Sertoli cell barrier|368.47|ARID4B,ARID4A|
|GID complex|276.35|WDR26,MAEA|
|negative regulation of calcium ion import across plasma membrane|276.35|PPP3R1,PPP3CA|
|calcineurin complex|221.08|PPP3CA,ITPR1|
|calcium-dependent protein serine/threonine phosphatase activity|184.23|PPP3R1,PPP3CA|
|calcineurin-NFAT signaling cascade|118.44|PPP3R1,PPP3CA,NFATC3|
|cyclosporin A binding|103.63|PPP3R1,PPP3CA,NKTR|
|calcineurin-mediated signaling|97.54|PPP3R1,PPP3CA,NFATC3|
|positive regulation of calcium-mediated signaling|41.45|PPP3R1,PPP3CA,PLCG2|
|negative regulation of calcium ion transmembrane transport|41.45|FKBP1A,PPP3R1,PPP3CA|
|regulation of stem cell population maintenance|31.14|ARID4B,CNOT2,SIRT6,ARID4A|
|regulation of calcium-mediated signaling|27.64|PPP3R1,PPP3CA,PLCG2,ITPR1|
|calcium-mediated signaling|17.94|PPP3R1,PPP3CA,BTK,NFATC3,PLCG2|
|intracellular protein-containing complex|6.31|YPEL5,PPP3R1,WDR26,CNOT8,PPP3CA,CNOT2,GID8,ITPR1,MAEA,KAT7|