====== Rapamycin 2μM plus FK-506 5μM R07 exp308 ======
==== Mechanism of Action ====
Allosteric mTORC1 inhibitor, forms ternary complex with FKBP12 and mTOR, attenuates protein synthesis and metabolism
  * **<color #00a2e8>Class / Subclass 1:</color>** Signal Transduction / Kinase Inhibitor
  * **<color #00a2e8>Class / Subclass 2:</color>** Proteostasis / mTOR inhibitor



==== Technical Notes ====

<accordion collapsed='true'>
=== Rapamycin ===
<panel title='Protein References' collapsed='true'>
    * **<color #00a2e8>PubChem Name:</color>** %%Sirolimus%%
    * **<color #00a2e8>Synonyms:</color>** Sirolimus; AY 22989
    * **<color #00a2e8>CAS #:</color>** 53123-88-9
    * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/5284616|5284616]]
    * **<color #00a2e8>IUPAC:</color>** %%(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%%
    * **<color #00a2e8>INCHI Name:</color>** 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
    * **<color #00a2e8>INCHI Key:</color>** QFJCIRLUMZQUOT-HPLJOQBZSA-N
    * **<color #00a2e8>Molecular Weight:</color>** 914.2
    * **<color #00a2e8>Canonical SMILES:</color>** 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
    * **<color #00a2e8>Isomeric SMILES:</color>** 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
    * **<color #00a2e8>Molecular Formula:</color>** C51H79NO13
{{:chemogenomics:structures:chem-0016.svg?nolink}}
</panel>


<panel title='Protein Supplier' collapsed='true'>
    * **<color #00a2e8>Supplier Name:</color>** LC Laboratories
    * **<color #00a2e8>Catalog #:</color>** R-5000
    * **<color #00a2e8>Lot #:</color>** ASW-130
</panel>


<panel title='Protein Characterization' collapsed='true'>
    * **<color #00a2e8>HRMS (ESI-TOF) m/z:</color>** (M+Na)+ Calcd for C51H79NO13 936.54436; found 936.54366
</panel>





=== FK-506 ===
<panel title='Protein References' collapsed='true'>
    * **<color #00a2e8>PubChem Name:</color>** %%Tacrolimus%%
    * **<color #00a2e8>Synonyms:</color>** FK506; Fujimycin; FR900506
    * **<color #00a2e8>CAS #:</color>** 104987-11-3
    * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/445643|445643]]
    * **<color #00a2e8>IUPAC:</color>** %%(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-1,14-dihydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone%%
    * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C44H69NO12/c1-10-13-31-19-25(2)18-26(3)20-37(54-8)40-38(55-9)22-28(5)44(52,57-40)41(49)42(50)45-17-12-11-14-32(45)43(51)56-39(29(6)34(47)24-35(31)48)27(4)21-30-15-16-33(46)36(23-30)53-7/h10,19,21,26,28-34,36-40,46-47,52H,1,11-18,20,22-24H2,2-9H3/b25-19+,27-21+/t26-,28+,29+,30-,31+,32-,33+,34-,36+,37-,38-,39+,40+,44+/m0/s1
    * **<color #00a2e8>INCHI Key:</color>** QJJXYPPXXYFBGM-LFZNUXCKSA-N
    * **<color #00a2e8>Molecular Weight:</color>** 804
    * **<color #00a2e8>Canonical SMILES:</color>** CC1CC(C2C(CC(C(O2)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C(CC(=O)C(C=C(C1)C)CC=C)O)C)C(=CC4CCC(C(C4)OC)O)C)O)C)OC)OC
    * **<color #00a2e8>Isomeric SMILES:</color>** C[C@@H]1C[C@@H]([C@@H]2[C@H](C[C@H]([C@@](O2)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@@H]([C@@H]([C@H](CC(=O)[C@@H](/C=C(/C1)\\C)CC=C)O)C)/C(=C/[C@@H]4CC[C@H]([C@@H](C4)OC)O)/C)O)C)OC)OC
    * **<color #00a2e8>Molecular Formula:</color>** C44H69NO12
{{:chemogenomics:structures:chem-0213.svg?nolink}}
</panel>


<panel title='Protein Supplier' collapsed='true'>
    * **<color #00a2e8>Supplier Name:</color>** Toronto Research Chemicals
    * **<color #00a2e8>Catalog #:</color>** F370000
    * **<color #00a2e8>Lot #:</color>** N/A
</panel>


<panel title='Protein Characterization' collapsed='true'>
    * **<color #00a2e8>HRMS (ESI-TOF) m/z:</color>** (M+Na)+ Calcd for C44H69NO12 826.4712; found 826.47365
</panel>




===Rapamycin+FK-506===
<panel title='Dose Response Curve' collapsed='true'>
    * **<color #00a2e8>Platform ID:</color>** FK-506_5uM_Rapamycin
    * **<color #00a2e8>Min:</color>** -29.7157; **<color #00a2e8>Max:</color>** 97.3162
{{:chemogenomics:dose_response:dr_484.png?nolink&500 |}}
\\ 
\\ 
\\ 
\\ 
|< 300px 100px 200px >|
^ IC   ^ Concentration (µM) ^
| IC10  |N/A    |
| IC20  |8.9811    |
| IC30  |10.1581    |
| IC40  |11.4624    |
| IC50  |12.9843    |
| IC60  |N/A    |
| IC70  |N/A    |
| IC80  |N/A    |
| IC90  |N/A    |
\\ 
\\ 
\\ 


The dose response curve for Rapamycin is also available at:
  * [[results:exp429|exp429]]
  * [[results:exp29|exp29]]
  * [[results:exp30|exp30]]
  * [[results:exp306|exp306]]
The dose response curve for FK-506 is also available at:
  * [[results:exp358|exp358]]
  * [[results:exp359|exp359]]
</panel>


</accordion>
==== Screen Summary ====
    * **<color #00a2e8>Round</color>**: 07
    * **<color #00a2e8>Dose</color>**: 2µM + 5µM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 5.6
    * **<color #00a2e8>Numbers of reads</color>**: 17119439


==== 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^
|1/5|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Rapamycin_2uM_FK-506_5uM_Round-7_exp308.txt|Scores]]</color>|<button type="primary" size="sm" modal="ScorePlot">View</button>|<button type="primary" size="sm" modal="modal_hits">View</button>|<button type="primary" size="sm" modal="modal_screen_similarity">View</button>|<button type="default" size="sm" modal="modal_go_sensitive">View</button>|<button type="primary" size="sm" modal="modal_go_resistant">View</button>|
<modal id='ScorePlot' size='lg' title='Rapamycin 2μM plus FK-506 5μM R07 exp308'>
{{:chemogenomics:cranks_plots:exp308.png?nolink}}
</modal>


<modal id="modal_hits" size="sm" title="Top 30 S/R Genes">
^Gene^CRANKS Score^FDR^
|[[:human_genes:U:UXS1|UXS1]]|-3.68|<0.01|
|[[:human_genes:E:ERCC2|ERCC2]]|-2.96|0.15|
|[[:human_genes:S:SCYL1|SCYL1]]|-2.55|0.14|
|[[:human_genes:S:SENP1|SENP1]]|-2.51|0.15|
|[[:human_genes:L:LAMTOR4|LAMTOR4]]|-2.49|0.15|
|[[:human_genes:H:HTR3E|HTR3E]]|-2.44|0.15|
|[[:human_genes:F:FLVCR1|FLVCR1]]|-2.37|0.15|
|[[:human_genes:N:NME6|NME6]]|-2.32|0.15|
|[[:human_genes:T:TADA1|TADA1]]|-2.27|0.16|
|[[:human_genes:T:TMEM230|TMEM230]]|-2.26|0.22|
|[[:human_genes:P:PCIF1|PCIF1]]|-2.25|0.17|
|[[:human_genes:R:RHOA|RHOA]]|-2.22|0.18|
|[[:human_genes:C:CEPT1|CEPT1]]|-2.14|0.22|
|[[:human_genes:D:DCLRE1B|DCLRE1B]]|-2.14|0.22|
|[[:human_genes:Z:ZNF688|ZNF688]]|-2.13|0.33|
|[[:human_genes:C:CBFB|CBFB]]|-2.12|0.22|
|[[:human_genes:Y:YWHAE|YWHAE]]|-2.12|0.22|
|[[:human_genes:B:BANF1|BANF1]]|-2.12|0.33|
|[[:human_genes:T:TBCD|TBCD]]|-2.08|0.33|
|[[:human_genes:E:ERG|ERG]]|-2.06|0.33|
|[[:human_genes:P:PIAS4|PIAS4]]|-2.06|0.33|
|[[:human_genes:S:SLC7A11|SLC7A11]]|-2.02|0.33|
|[[:human_genes:F:FLI1|FLI1]]|-2.02|0.33|
|[[:human_genes:S:SNF8|SNF8]]|-2.01|0.33|
|[[:human_genes:P:PRUNE|PRUNE]]|-2.01|0.33|
|[[:human_genes:P:PSPC1|PSPC1]]|-2.01|0.33|
|[[:human_genes:T:TCOF1|TCOF1]]|-2.00|0.33|
|[[:human_genes:U:UMPS|UMPS]]|-1.98|0.71|
|[[:human_genes:L:LAMTOR2|LAMTOR2]]|-1.98|0.33|
|[[:human_genes:P:PRRC2C|PRRC2C]]|-1.98|0.33|
|[[:human_genes:D:DEF6|DEF6]]|2.01|0.40|
|[[:human_genes:O:ORC6|ORC6]]|2.01|0.61|
|[[:human_genes:C:CLPP|CLPP]]|2.01|0.40|
|[[:human_genes:M:MKNK2|MKNK2]]|2.02|0.28|
|[[:human_genes:C:C6orf48|C6orf48]]|2.04|0.26|
|[[:human_genes:S:SOX12|SOX12]]|2.07|0.43|
|[[:human_genes:P:PSMC3|PSMC3]]|2.07|0.62|
|[[:human_genes:D:DAZAP1|DAZAP1]]|2.09|0.21|
|[[:human_genes:S:SMG1|SMG1]]|2.12|0.18|
|[[:human_genes:A:ATL3|ATL3]]|2.13|0.18|
|[[:human_genes:E:ECHS1|ECHS1]]|2.13|0.18|
|[[:human_genes:N:NANS|NANS]]|2.18|0.16|
|[[:human_genes:T:TMSB15B|TMSB15B]]|2.24|0.61|
|[[:human_genes:X:XPNPEP3|XPNPEP3]]|2.30|0.10|
|[[:human_genes:Z:ZNF627|ZNF627]]|2.39|0.08|
|[[:human_genes:R:RPL38|RPL38]]|2.42|0.18|
|[[:human_genes:C:CDK8|CDK8]]|2.42|0.10|
|[[:human_genes:N:NAA15|NAA15]]|2.44|0.10|
|[[:human_genes:U:UBE2H|UBE2H]]|2.46|0.05|
|[[:human_genes:C:CNOT1|CNOT1]]|2.47|0.10|
|[[:human_genes:C:CNOT8|CNOT8]]|2.47|0.05|
|[[:human_genes:Y:YPEL5|YPEL5]]|2.52|0.05|
|[[:human_genes:P:POLE2|POLE2]]|2.54|0.39|
|[[:human_genes:C:CNOT2|CNOT2]]|2.64|0.03|
|[[:human_genes:C:CXorf56|CXorf56]]|2.64|0.05|
|[[:human_genes:C:CCDC6|CCDC6]]|2.67|0.03|
|[[:human_genes:G:GSK3B|GSK3B]]|2.84|0.02|
|[[:human_genes:P:PPWD1|PPWD1]]|2.94|0.14|
|[[:human_genes:T:TSC2|TSC2]]|3.50|<0.01|
|[[:human_genes:F:FKBP1A|FKBP1A]]|6.20|<0.01|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp306|Rapamycin 2μM R07 exp306]]|0.106|<button type="primary" size="small" modal="1">View</button>|
|[[:results:exp29|Rapamycin 1μM R00 exp29]]|0.102|<button type="primary" size="small" modal="2">View</button>|
|[[:results:exp307|Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307]]|0.095|<button type="primary" size="small" modal="3">View</button>|
|[[:results:exp30|Rapamycin 10μM R00 exp30]]|0.089|<button type="primary" size="small" modal="4">View</button>|
|[[:results:exp429|Rapamycin 0.001μM R08 exp429]]|0.066|<button type="primary" size="small" modal="5">View</button>|
|[[:results:exp351|Dexamethasone 0.006μM R07 exp351]]|0.056|<button type="primary" size="small" modal="6">View</button>|
|[[:results:exp242|Radicicol 0.16μM R05 exp242]]|0.055|<button type="primary" size="small" modal="7">View</button>|
</modal>


<modal id="1" size="lg" title="Rapamycin 2μM plus FK-506 5μM R07 exp308  vs  Rapamycin 2μM R07 exp306">
{{:chemogenomics:comparison_plots:exp306_vs_exp308.png?nolink |}}
</modal>

<modal id="2" size="lg" title="Rapamycin 1μM R00 exp29  vs  Rapamycin 2μM plus FK-506 5μM R07 exp308">
{{:chemogenomics:comparison_plots:exp29_vs_exp308.png?nolink |}}
</modal>

<modal id="3" size="lg" title="Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307  vs  Rapamycin 2μM plus FK-506 5μM R07 exp308">
{{:chemogenomics:comparison_plots:exp307_vs_exp308.png?nolink |}}
</modal>

<modal id="4" size="lg" title="Rapamycin 10μM R00 exp30  vs  Rapamycin 2μM plus FK-506 5μM R07 exp308">
{{:chemogenomics:comparison_plots:exp30_vs_exp308.png?nolink |}}
</modal>

<modal id="5" size="lg" title="Rapamycin 0.001μM R08 exp429  vs  Rapamycin 2μM plus FK-506 5μM R07 exp308">
{{:chemogenomics:comparison_plots:exp308_vs_exp429.png?nolink |}}
</modal>

<modal id="6" size="lg" title="Dexamethasone 0.006μM R07 exp351  vs  Rapamycin 2μM plus FK-506 5μM R07 exp308">
{{:chemogenomics:comparison_plots:exp308_vs_exp351.png?nolink |}}
</modal>

<modal id="7" size="lg" title="Radicicol 0.16μM R05 exp242  vs  Rapamycin 2μM plus FK-506 5μM R07 exp308">
{{:chemogenomics:comparison_plots:exp242_vs_exp308.png?nolink |}}
</modal>



<modal id="modal_go_sensitive" size="lg" title="Top 30 sensitive GO terms">No GO term hits below threshold. (FDR <0.05)</modal>
<modal id="modal_go_resistant" size="lg" title="Top 30 resistant GO terms">
^GO Term^Fold Change^Genes^
|poly(A)-specific ribonuclease activity|138.16|CNOT2,CNOT8,CNOT1|
</modal>