====== Actinomycin-D 0.01μM R00 exp4 ======
==== Mechanism of Action ====
Inhibits RNA polymerases, intercalates DNA, prevents chain elongation
  * **<color #00a2e8>Class / Subclass 1:</color>** Gene Regulation / Transcription Inhibitor




==== Technical Notes ====
<accordion collapsed='true'>
<panel title='Protein References' collapsed='true'>
    * **<color #00a2e8>PubChem Name:</color>** %%Dactinomycin%%
    * **<color #00a2e8>Synonyms:</color>** Dactinomycin; Actinomycin IV
    * **<color #00a2e8>CAS #:</color>** 50-76-0
    * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/457193|457193]]
    * **<color #00a2e8>IUPAC:</color>** %%2-amino-4,6-dimethyl-3-oxo-1-N,9-N-bis[(3R,6S,7R,10S,16S)-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-3,10-di(propan-2-yl)-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]phenoxazine-1,9-dicarboxamide%%
    * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C62H86N12O16/c1-27(2)42-59(84)73-23-17-19-36(73)57(82)69(13)25-38(75)71(15)48(29(5)6)61(86)88-33(11)44(55(80)65-42)67-53(78)35-22-21-31(9)51-46(35)64-47-40(41(63)50(77)32(10)52(47)90-51)54(79)68-45-34(12)89-62(87)49(30(7)8)72(16)39(76)26-70(14)58(83)37-20-18-24-74(37)60(85)43(28(3)4)66-56(45)81/h21-22,27-30,33-34,36-37,42-45,48-49H,17-20,23-26,63H2,1-16H3,(H,65,80)(H,66,81)(H,67,78)(H,68,79)/t33-,34-,36+,37+,42-,43-,44+,45+,48+,49+/m1/s1
    * **<color #00a2e8>INCHI Key:</color>** RJURFGZVJUQBHK-IIXSONLDSA-N
    * **<color #00a2e8>Molecular Weight:</color>** 1255.4
    * **<color #00a2e8>Canonical SMILES:</color>** CC1C(C(=O)NC(C(=O)N2CCCC2C(=O)N(CC(=O)N(C(C(=O)O1)C(C)C)C)C)C(C)C)NC(=O)C3=C4C(=C(C=C3)C)OC5=C(C(=O)C(=C(C5=N4)C(=O)NC6C(OC(=O)C(N(C(=O)CN(C(=O)C7CCCN7C(=O)C(NC6=O)C(C)C)C)C)C(C)C)C)N)C
    * **<color #00a2e8>Isomeric SMILES:</color>** C[C@@H]1[C@@H](C(=O)N[C@@H](C(=O)N2CCC[C@H]2C(=O)N(CC(=O)N([C@H](C(=O)O1)C(C)C)C)C)C(C)C)NC(=O)C3=C4C(=C(C=C3)C)OC5=C(C(=O)C(=C(C5=N4)C(=O)N[C@H]6[C@H](OC(=O)[C@@H](N(C(=O)CN(C(=O)[C@@H]7CCCN7C(=O)[C@H](NC6=O)C(C)C)C)C)C(C)C)C)N)C
    * **<color #00a2e8>Molecular Formula:</color>** C62H86N12O16
{{:chemogenomics:structures:chem-0002.svg?nolink}}
</panel>


<panel title='Protein Supplier' collapsed='true'>
    * **<color #00a2e8>Supplier Name:</color>** Sigma-Aldrich
    * **<color #00a2e8>Catalog #:</color>** A1410
    * **<color #00a2e8>Lot #:</color>** N/A
</panel>


<panel title='Protein Characterization' collapsed='true'>
    * **<color #00a2e8>HRMS (ESI-TOF) m/z:</color>** (M+H)+ Calcd for C62H86N12O16 1255.63575; found 1255.63738
</panel>


<panel title='Dose Response Curve' collapsed='true'>
    * **<color #00a2e8>Platform ID:</color>** Actinomycin_D
    * **<color #00a2e8>Min:</color>** -23.7457; **<color #00a2e8>Max:</color>** 97.9710
{{:chemogenomics:dose_response:dr_254.png?nolink&500 |}}
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|< 300px 100px 200px >|
^ IC   ^ Concentration (µM) ^
| IC10  |N/A    |
| IC20  |0.0002    |
| IC30  |0.0002    |
| IC40  |0.0002    |
| IC50  |0.0002    |
| IC60  |N/A    |
| IC70  |N/A    |
| IC80  |N/A    |
| IC90  |N/A    |
\\ 
</panel>
</accordion>
==== Screen Summary ====
    * **<color #00a2e8>Round</color>**: 00
    * **<color #00a2e8>Dose</color>**: 10nM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 0.3
    * **<color #00a2e8>Numbers of reads</color>**: 9758344


==== 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^
|1/17|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Actinomycin_D_0.01uM_Round-0_exp4.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="primary" 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='Actinomycin-D 0.01μM R00 exp4'>
{{:chemogenomics:cranks_plots:exp4.png?nolink}}
</modal>


<modal id="modal_hits" size="sm" title="Top 30 S/R Genes">
^Gene^CRANKS Score^FDR^
|[[:human_genes:P:PRAMEF25|PRAMEF25]]|-4.31|0.08|
|[[:human_genes:P:PRAMEF26|PRAMEF26]]|-4.26|0.08|
|[[:human_genes:G:GUSB|GUSB]]|-3.07|0.03|
|[[:human_genes:R:RPS11|RPS11]]|-2.95|0.23|
|[[:human_genes:R:RBCK1|RBCK1]]|-2.72|0.08|
|[[:human_genes:E:ESPL1|ESPL1]]|-2.70|0.23|
|[[:human_genes:G:GOLGA6L1|GOLGA6L1]]|-2.63|0.46|
|[[:human_genes:E:EGR2|EGR2]]|-2.55|0.30|
|[[:human_genes:A:ADIPOR2|ADIPOR2]]|-2.54|0.08|
|[[:human_genes:A:ATP6V1E1|ATP6V1E1]]|-2.46|0.17|
|[[:human_genes:S:SRGAP2C|SRGAP2C]]|-2.46|0.46|
|[[:human_genes:S:SMU1|SMU1]]|-2.41|0.46|
|[[:human_genes:I:INCENP|INCENP]]|-2.34|0.23|
|[[:human_genes:S:SF3A1|SF3A1]]|-2.33|0.64|
|[[:human_genes:A:ATP6V1B2|ATP6V1B2]]|-2.32|0.23|
|[[:human_genes:P:PCYT1A|PCYT1A]]|-2.31|0.17|
|[[:human_genes:A:ATP6V0B|ATP6V0B]]|-2.29|0.33|
|[[:human_genes:P:POLA1|POLA1]]|-2.27|0.67|
|[[:human_genes:S:STAG1|STAG1]]|-2.24|0.35|
|[[:human_genes:G:GAGE2A|GAGE2A]]|-2.23|0.60|
|[[:human_genes:P:PAG1|PAG1]]|-2.17|0.33|
|[[:human_genes:P:PSMD7|PSMD7]]|-2.16|0.56|
|[[:human_genes:M:MTX1|MTX1]]|-2.15|0.33|
|[[:human_genes:O:OSBPL6|OSBPL6]]|-2.13|0.28|
|[[:human_genes:A:ACTL7A|ACTL7A]]|-2.12|0.28|
|[[:human_genes:C:CKMT1B|CKMT1B]]|-2.12|0.33|
|[[:human_genes:H:HMHA1|HMHA1]]|-2.09|0.52|
|[[:human_genes:C:COPB2|COPB2]]|-2.08|0.52|
|[[:human_genes:N:NAV2|NAV2]]|-2.08|0.35|
|[[:human_genes:S:SMAGP|SMAGP]]|-2.07|0.32|
|[[:human_genes:R:RETSAT|RETSAT]]|2.16|0.12|
|[[:human_genes:P:PPP2R2A|PPP2R2A]]|2.19|0.15|
|[[:human_genes:S:SLAMF9|SLAMF9]]|2.21|0.10|
|[[:human_genes:S:SUMO2|SUMO2]]|2.23|0.20|
|[[:human_genes:U:UBLCP1|UBLCP1]]|2.25|0.08|
|[[:human_genes:C:C10orf118|C10orf118]]|2.25|0.14|
|[[:human_genes:K:KARS|KARS]]|2.27|0.13|
|[[:human_genes:K:KCMF1|KCMF1]]|2.28|0.08|
|[[:human_genes:T:TBP|TBP]]|2.32|0.11|
|[[:human_genes:Z:ZNF571|ZNF571]]|2.40|0.04|
|[[:human_genes:C:CSNK2B|CSNK2B]]|2.40|0.08|
|[[:human_genes:S:SRPRB|SRPRB]]|2.43|0.04|
|[[:human_genes:C:CCT7|CCT7]]|2.57|0.02|
|[[:human_genes:S:SRPR|SRPR]]|2.60|0.02|
|[[:human_genes:C:CBX3|CBX3]]|2.70|0.02|
|[[:human_genes:P:POLR3A|POLR3A]]|2.72|0.01|
|[[:human_genes:R:RPL11|RPL11]]|2.75|0.15|
|[[:human_genes:M:MARS|MARS]]|2.76|0.15|
|[[:human_genes:C:CCT6A|CCT6A]]|2.78|0.02|
|[[:human_genes:G:GTF3C2|GTF3C2]]|2.79|0.03|
|[[:human_genes:O:OTUD5|OTUD5]]|2.81|0.02|
|[[:human_genes:E:ENO1|ENO1]]|2.83|0.03|
|[[:human_genes:P:PANX1|PANX1]]|2.83|<0.01|
|[[:human_genes:S:SRP19|SRP19]]|2.88|0.01|
|[[:human_genes:U:USP27X|USP27X]]|2.97|0.33|
|[[:human_genes:S:SRP72|SRP72]]|3.10|<0.01|
|[[:human_genes:E:ENY2|ENY2]]|3.17|<0.01|
|[[:human_genes:S:SRP68|SRP68]]|3.33|<0.01|
|[[:human_genes:M:MAPK14|MAPK14]]|3.57|<0.01|
|[[:human_genes:S:SRP54|SRP54]]|3.89|<0.01|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp22|MLN-4924 2μM R00 exp22]]|0.074|<button type="primary" size="small" modal="1">View</button>|
|[[:results:exp7|Bortezomib 0.05μM R00 exp7]]|0.072|<button type="primary" size="small" modal="2">View</button>|
|[[:results:exp19|Etoposide 1μM R00 exp19]]|0.057|<button type="primary" size="small" modal="3">View</button>|
|[[:results:exp28|Pimelic-diphenylamide-106 5μM R00 exp28]]|0.057|<button type="primary" size="small" modal="4">View</button>|
|[[:results:exp17|DABN 20μM R00 exp17]]|0.056|<button type="primary" size="small" modal="5">View</button>|
</modal>


<modal id="1" size="lg" title="Actinomycin-D 0.01μM R00 exp4  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp22_vs_exp4.png?nolink |}}
</modal>

<modal id="2" size="lg" title="Actinomycin-D 0.01μM R00 exp4  vs  Bortezomib 0.05μM R00 exp7">
{{:chemogenomics:comparison_plots:exp4_vs_exp7.png?nolink |}}
</modal>

<modal id="3" size="lg" title="Actinomycin-D 0.01μM R00 exp4  vs  Etoposide 1μM R00 exp19">
{{:chemogenomics:comparison_plots:exp19_vs_exp4.png?nolink |}}
</modal>

<modal id="4" size="lg" title="Actinomycin-D 0.01μM R00 exp4  vs  Pimelic-diphenylamide-106 5μM R00 exp28">
{{:chemogenomics:comparison_plots:exp28_vs_exp4.png?nolink |}}
</modal>

<modal id="5" size="lg" title="Actinomycin-D 0.01μM R00 exp4  vs  DABN 20μM R00 exp17">
{{:chemogenomics:comparison_plots:exp17_vs_exp4.png?nolink |}}
</modal>



<modal id="modal_go_sensitive" size="lg" title="Top 30 sensitive GO terms">
^GO Term^Fold Change^Genes^
|ATPase-coupled ion transmembrane transporter activity|86.52|ATP6V1E1,ATP6V1B2,ATP6V0B|
|ATPase activity, coupled to transmembrane movement of ions, rotational mechanism|86.52|ATP6V1E1,ATP6V1B2,ATP6V0B|
|vacuolar proton-transporting V-type ATPase complex|82.91|ATP6V1E1,ATP6V1B2,ATP6V0B|
|proton-transporting V-type ATPase complex|73.70|ATP6V1E1,ATP6V1B2,ATP6V0B|
</modal>
<modal id="modal_go_resistant" size="lg" title="Top 30 resistant GO terms">
^GO Term^Fold Change^Genes^
|SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition|552.77|SRP54,SRP19,SRPRA|
|endoplasmic reticulum signal peptide binding|552.77|SRP54,SRP68|
|signal recognition particle|442.21|SRP54,SRP68,SRP72,SRP19|
|7S RNA binding|368.51|SRP54,SRP68,SRP72,SRP19|
|signal recognition particle, endoplasmic reticulum targeting|331.66|SRP54,SRP72,SRP19|
|signal recognition particle binding|276.38|SRP68,SRP72,SRPRA|
|SRP-dependent cotranslational protein targeting to membrane|207.29|SRP54,SRP68,SRP72,SRP19,SRPRA,SRPRB|
|cotranslational protein targeting to membrane|157.93|SRP54,SRP68,SRP72,SRP19,SRPRA,SRPRB|
|protein targeting to ER|92.13|SRP54,SRP68,SRP72,SRP19,SRPRA,SRPRB|
|establishment of protein localization to endoplasmic reticulum|69.10|SRP54,SRP68,SRP19,SRPRA,SRPRB|
|protein localization to endoplasmic reticulum|51.82|SRP54,SRP68,SRP72,SRP19,SRPRA,SRPRB|
|positive regulation of telomere maintenance via telomerase|50.25|CCT6A,CCT7,MAP3K4|
|positive regulation of telomere maintenance via telomere lengthening|46.06|CCT6A,CCT7,MAP3K4|
|protein targeting to membrane|37.27|SRP54,SRP68,SRP72,SRP19,SRPRA,SRPRB|
|ribonucleoprotein complex binding|17.72|SRP54,SRP68,SRP72,SRP19,SRPRA|
|protein targeting|15.48|SRP54,SRP68,SRP72,SRP19,RPL11,SRPRA,SRPRB|
|establishment of protein localization to membrane|12.80|SRP54,SRP68,SRP72,SRPRA,SRPRB|
|establishment of protein localization to organelle|9.96|SRP54,SRP68,SRP72,SRP19,SRPRA,SRPRB|
</modal>