====== Rapamycin 2μM R07 exp306 ======
==== 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**: 07
* **Dose**: 2µM
* **Days of incubation**: 8
* **Doublings**: 4.6
* **Numbers of reads**: 22492524
==== 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^
|9/28|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Rapamycin_2uM_Round-7_exp306.txt|Scores]]||||||
{{:chemogenomics:cranks_plots:exp306.png?nolink}}
^Gene^CRANKS Score^FDR^
|[[:human_genes:U:UXS1|UXS1]]|-3.13|<0.01|
|[[:human_genes:G:GNA13|GNA13]]|-2.91|0.01|
|[[:human_genes:R:RHOA|RHOA]]|-2.90|0.01|
|[[:human_genes:F:FBXO11|FBXO11]]|-2.77|0.01|
|[[:human_genes:C:CUL2|CUL2]]|-2.76|0.01|
|[[:human_genes:V:VPS25|VPS25]]|-2.71|0.22|
|[[:human_genes:A:ARHGEF1|ARHGEF1]]|-2.64|0.02|
|[[:human_genes:U:UBA5|UBA5]]|-2.64|0.02|
|[[:human_genes:E:EP300|EP300]]|-2.64|0.15|
|[[:human_genes:T:TAF5L|TAF5L]]|-2.60|0.05|
|[[:human_genes:T:TCF4|TCF4]]|-2.59|0.03|
|[[:human_genes:D:DYX1C1|DYX1C1]]|-2.49|0.04|
|[[:human_genes:F:FZR1|FZR1]]|-2.37|0.13|
|[[:human_genes:T:TRAK2|TRAK2]]|-2.37|0.13|
|[[:human_genes:A:ATP9A|ATP9A]]|-2.28|0.12|
|[[:human_genes:W:WHSC1L1|WHSC1L1]]|-2.27|0.12|
|[[:human_genes:Y:YRDC|YRDC]]|-2.22|0.30|
|[[:human_genes:Z:ZFX|ZFX]]|-2.22|0.13|
|[[:human_genes:G:GATAD2A|GATAD2A]]|-2.21|0.13|
|[[:human_genes:S:SEPHS2|SEPHS2]]|-2.20|0.13|
|[[:human_genes:T:TSPYL2|TSPYL2]]|-2.20|0.31|
|[[:human_genes:P:PRAMEF25|PRAMEF25]]|-2.17|0.64|
|[[:human_genes:C:CCDC101|CCDC101]]|-2.16|0.15|
|[[:human_genes:P:PRAMEF26|PRAMEF26]]|-2.15|0.64|
|[[:human_genes:H:HNRNPA0|HNRNPA0]]|-2.12|0.17|
|[[:human_genes:A:ATP2B1|ATP2B1]]|-2.12|0.26|
|[[:human_genes:U:UBN2|UBN2]]|-2.09|0.20|
|[[:human_genes:L:LIPN|LIPN]]|-2.08|0.20|
|[[:human_genes:P:POLR2J2|POLR2J2]]|-2.06|0.60|
|[[:human_genes:R:RASGRP1|RASGRP1]]|-2.05|0.22|
|[[:human_genes:N:NAA40|NAA40]]|2.32|0.14|
|[[:human_genes:G:GLYR1|GLYR1]]|2.33|0.04|
|[[:human_genes:C:CWC27|CWC27]]|2.33|0.04|
|[[:human_genes:C:CDH22|CDH22]]|2.41|0.03|
|[[:human_genes:A:ANP32A|ANP32A]]|2.43|0.03|
|[[:human_genes:G:GSK3A|GSK3A]]|2.46|0.02|
|[[:human_genes:A:ARID4B|ARID4B]]|2.47|0.04|
|[[:human_genes:T:TAF15|TAF15]]|2.49|0.07|
|[[:human_genes:T:TSC2|TSC2]]|2.52|0.02|
|[[:human_genes:C:CREB1|CREB1]]|2.60|0.01|
|[[:human_genes:S:SKIV2L|SKIV2L]]|2.66|0.04|
|[[:human_genes:P:PGM3|PGM3]]|2.69|0.02|
|[[:human_genes:N:NANS|NANS]]|2.73|<0.01|
|[[:human_genes:M:MMGT1|MMGT1]]|2.81|<0.01|
|[[:human_genes:G:GID8|GID8]]|2.88|<0.01|
|[[:human_genes:M:MEMO1|MEMO1]]|2.88|<0.01|
|[[:human_genes:M:MIR205HG|MIR205HG]]|2.89|0.33|
|[[:human_genes:B:BTK|BTK]]|2.98|<0.01|
|[[:human_genes:P:PPP3CA|PPP3CA]]|3.13|0.00|
|[[:human_genes:D:DAZAP1|DAZAP1]]|3.29|0.00|
|[[:human_genes:F:FAM122A|FAM122A]]|3.38|0.00|
|[[:human_genes:C:CDK8|CDK8]]|3.54|0.00|
|[[:human_genes:M:MAEA|MAEA]]|3.58|0.00|
|[[:human_genes:W:WDR26|WDR26]]|3.88|0.00|
|[[:human_genes:C:CNOT8|CNOT8]]|3.91|0.00|
|[[:human_genes:P:PPP3R1|PPP3R1]]|4.20|0.00|
|[[:human_genes:C:CNOT2|CNOT2]]|5.19|0.00|
|[[:human_genes:U:UBE2H|UBE2H]]|5.95|0.00|
|[[:human_genes:Y:YPEL5|YPEL5]]|6.34|0.00|
|[[:human_genes:F:FKBP1A|FKBP1A]]|7.62|0.00|
^Screen^Correlation^Plot^
|[[:results:exp82|Torin1 0.08μM R02 exp82]]|0.062||
|[[:results:exp418|Tunicamycin 0.04μM R07 exp418]]|0.051||
|[[:results:exp30|Rapamycin 10μM R00 exp30]]|0.142||
|[[:results:exp29|Rapamycin 1μM R00 exp29]]|0.14||
|[[:results:exp429|Rapamycin 0.001μM R08 exp429]]|0.124||
|[[:results:exp307|Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307]]|0.107||
|[[:results:exp308|Rapamycin 2μM plus FK-506 5μM R07 exp308]]|0.106||
|[[:results:exp365|I-BRD9 4μM R07 exp365]]|0.071||
|[[:results:exp352|Dexamethasone 0.006 to 0.015μM on day4 R07 exp352]]|0.061||
|[[:results:exp485|GSK626616 14μM R08 exp485]]|0.054||
|[[:results:exp504|MK2206 4μM R08 exp504]]|0.053||
|[[:results:exp488|Hippuristanol 0.12μM R08 exp488]]|0.052||
{{:chemogenomics:comparison_plots:exp306_vs_exp82.png?nolink |}}
{{:chemogenomics:comparison_plots:exp306_vs_exp418.png?nolink |}}
{{:chemogenomics:comparison_plots:exp30_vs_exp306.png?nolink |}}
{{:chemogenomics:comparison_plots:exp29_vs_exp306.png?nolink |}}
{{:chemogenomics:comparison_plots:exp306_vs_exp429.png?nolink |}}
{{:chemogenomics:comparison_plots:exp306_vs_exp307.png?nolink |}}
{{:chemogenomics:comparison_plots:exp306_vs_exp308.png?nolink |}}
{{:chemogenomics:comparison_plots:exp306_vs_exp365.png?nolink |}}
{{:chemogenomics:comparison_plots:exp306_vs_exp352.png?nolink |}}
{{:chemogenomics:comparison_plots:exp306_vs_exp485.png?nolink |}}
{{:chemogenomics:comparison_plots:exp306_vs_exp504.png?nolink |}}
{{:chemogenomics:comparison_plots:exp306_vs_exp488.png?nolink |}}
No GO term hits below threshold. (FDR <0.05)
^GO Term^Fold Change^Genes^
|cyclosporin A binding|103.62|PPP3R1,PPP3CA,CWC27|