====== MLN-4924 2μM R00 exp22 ======
==== Mechanism of Action ====
Inhibits NEDD8-activating enzyme (NAE), prevents activity of cullin-RING ligase (CRL) E3 enzymes
  * **<color #00a2e8>Class / Subclass 1:</color>** Proteostasis / NEDDylation Inhibitor




==== Technical Notes ====
<accordion collapsed='true'>
<panel title='Protein References' collapsed='true'>
    * **<color #00a2e8>PubChem Name:</color>** %%Pevonedistat%%
    * **<color #00a2e8>Synonyms:</color>** MLN4924
    * **<color #00a2e8>CAS #:</color>** 905579-51-3
    * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/16720766|16720766]]
    * **<color #00a2e8>IUPAC:</color>** %%[(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl sulfamate%%
    * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C21H25N5O4S/c22-31(28,29)30-11-14-9-15(10-19(14)27)26-8-7-17-20(23-12-24-21(17)26)25-18-6-5-13-3-1-2-4-16(13)18/h1-4,7-8,12,14-15,18-19,27H,5-6,9-11H2,(H2,22,28,29)(H,23,24,25)/t14-,15+,18-,19-/m0/s1
    * **<color #00a2e8>INCHI Key:</color>** MPUQHZXIXSTTDU-QXGSTGNESA-N
    * **<color #00a2e8>Molecular Weight:</color>** 443.5
    * **<color #00a2e8>Canonical SMILES:</color>** C1CC2=CC=CC=C2C1NC3=C4C=CN(C4=NC=N3)C5CC(C(C5)O)COS(=O)(=O)N
    * **<color #00a2e8>Isomeric SMILES:</color>** C1CC2=CC=CC=C2[C@H]1NC3=C4C=CN(C4=NC=N3)[C@@H]5C[C@H]([C@H](C5)O)COS(=O)(=O)N
    * **<color #00a2e8>Molecular Formula:</color>** C21H25N5O4S
{{:chemogenomics:structures:chem-0012.svg?nolink}}
</panel>


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


<panel title='Protein Characterization' collapsed='true'>
Characterization data not available.
</panel>


<panel title='Dose Response Curve' collapsed='true'>
    * **<color #00a2e8>Platform ID:</color>** MLN-4924
    * **<color #00a2e8>Min:</color>** 0.2392; **<color #00a2e8>Max:</color>** 97.5121
{{:chemogenomics:dose_response:dr_269.png?nolink&500 |}}
\\ 
\\ 
\\ 
\\ 
|< 300px 100px 200px >|
^ IC   ^ Concentration (µM) ^
| IC10  |N/A    |
| IC20  |0.0970    |
| IC30  |0.1416    |
| IC40  |0.1931    |
| IC50  |0.2566    |
| 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>**: 2µM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 0.6
    * **<color #00a2e8>Numbers of reads</color>**: 12173332


==== 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^
|1/34|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/MLN-4924_2uM_Round-0_exp22.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='MLN-4924 2μM R00 exp22'>
{{:chemogenomics:cranks_plots:exp22.png?nolink}}
</modal>


<modal id="modal_hits" size="sm" title="Top 30 S/R Genes">
^Gene^CRANKS Score^FDR^
|[[:human_genes:C:COPB2|COPB2]]|-3.16|0.08|
|[[:human_genes:S:SLFN11|SLFN11]]|-2.91|0.03|
|[[:human_genes:A:AURKB|AURKB]]|-2.83|0.15|
|[[:human_genes:I:INCENP|INCENP]]|-2.75|0.08|
|[[:human_genes:P:PSMA7|PSMA7]]|-2.64|0.33|
|[[:human_genes:P:PSMB2|PSMB2]]|-2.64|0.21|
|[[:human_genes:P:PRIM1|PRIM1]]|-2.56|0.44|
|[[:human_genes:C:COX7A2L|COX7A2L]]|-2.54|0.08|
|[[:human_genes:P:POLE|POLE]]|-2.53|0.36|
|[[:human_genes:S:SPG7|SPG7]]|-2.53|0.12|
|[[:human_genes:K:KRI1|KRI1]]|-2.51|0.36|
|[[:human_genes:C:CNOT3|CNOT3]]|-2.50|0.12|
|[[:human_genes:D:DDX3X|DDX3X]]|-2.49|0.08|
|[[:human_genes:V:VPS52|VPS52]]|-2.45|0.12|
|[[:human_genes:A:AATF|AATF]]|-2.44|0.21|
|[[:human_genes:C:CXXC1|CXXC1]]|-2.40|0.10|
|[[:human_genes:C:CNOT2|CNOT2]]|-2.40|0.10|
|[[:human_genes:A:ATP6V1B2|ATP6V1B2]]|-2.40|0.12|
|[[:human_genes:P:POLR2L|POLR2L]]|-2.34|0.44|
|[[:human_genes:P:PSMD2|PSMD2]]|-2.31|0.19|
|[[:human_genes:S:SART1|SART1]]|-2.30|0.44|
|[[:human_genes:H:HEXIM1|HEXIM1]]|-2.28|0.12|
|[[:human_genes:N:NME6|NME6]]|-2.27|0.12|
|[[:human_genes:W:WAPAL|WAPAL]]|-2.26|0.15|
|[[:human_genes:A:ADIPOR2|ADIPOR2]]|-2.25|0.12|
|[[:human_genes:P:POLR2I|POLR2I]]|-2.23|0.12|
|[[:human_genes:S:SYS1|SYS1]]|-2.22|0.12|
|[[:human_genes:E:EXOSC1|EXOSC1]]|-2.22|0.12|
|[[:human_genes:K:KRT6B|KRT6B]]|-2.22|0.12|
|[[:human_genes:P:POLR2D|POLR2D]]|-2.20|0.19|
|[[:human_genes:T:TXNDC17|TXNDC17]]|2.34|0.04|
|[[:human_genes:M:MTOR|MTOR]]|2.36|0.09|
|[[:human_genes:T:TBP|TBP]]|2.40|0.05|
|[[:human_genes:P:POLR3H|POLR3H]]|2.43|0.02|
|[[:human_genes:P:POLR3B|POLR3B]]|2.45|0.04|
|[[:human_genes:E:EZH2|EZH2]]|2.46|0.07|
|[[:human_genes:N:NXT1|NXT1]]|2.53|0.01|
|[[:human_genes:C:CMTR2|CMTR2]]|2.55|0.01|
|[[:human_genes:K:KCMF1|KCMF1]]|2.56|0.01|
|[[:human_genes:T:TTI2|TTI2]]|2.63|0.04|
|[[:human_genes:P:PYROXD1|PYROXD1]]|2.69|0.06|
|[[:human_genes:M:MEAF6|MEAF6]]|2.71|0.01|
|[[:human_genes:R:RPE|RPE]]|2.72|0.01|
|[[:human_genes:T:TTI1|TTI1]]|2.77|<0.01|
|[[:human_genes:G:GTF3C3|GTF3C3]]|2.85|<0.01|
|[[:human_genes:R:RPTOR|RPTOR]]|2.93|<0.01|
|[[:human_genes:G:GTF3A|GTF3A]]|3.02|<0.01|
|[[:human_genes:C:CD9|CD9]]|3.03|<0.01|
|[[:human_genes:T:TAZ|TAZ]]|3.04|<0.01|
|[[:human_genes:O:OTUD5|OTUD5]]|3.11|<0.01|
|[[:human_genes:E:ENY2|ENY2]]|3.11|<0.01|
|[[:human_genes:P:PAX5|PAX5]]|3.15|<0.01|
|[[:human_genes:P:PLAA|PLAA]]|3.17|<0.01|
|[[:human_genes:R:RTCB|RTCB]]|3.24|<0.01|
|[[:human_genes:A:APAF1|APAF1]]|3.33|<0.01|
|[[:human_genes:P:PTRH2|PTRH2]]|3.40|<0.01|
|[[:human_genes:C:CDKN1A|CDKN1A]]|3.42|<0.01|
|[[:human_genes:B:BAK1|BAK1]]|3.46|<0.01|
|[[:human_genes:G:GMPPB|GMPPB]]|3.67|<0.01|
|[[:human_genes:T:TP53|TP53]]|5.93|<0.01|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp28|Pimelic-diphenylamide-106 5μM R00 exp28]]|0.126|<button type="primary" size="small" modal="1">View</button>|
|[[:results:exp531|THZ1 0.06μM R08 exp531]]|0.096|<button type="primary" size="small" modal="2">View</button>|
|[[:results:exp34|Rotenone 20μM R00 exp34]]|0.087|<button type="primary" size="small" modal="3">View</button>|
|[[:results:exp443|SNS-032 15μM R08 exp443]]|0.065|<button type="primary" size="small" modal="4">View</button>|
|[[:results:exp515|PU-H71 1μM R08 exp515]]|0.063|<button type="primary" size="small" modal="5">View</button>|
|[[:results:exp503|Mitomycin-C 0.06μM R08 exp503]]|0.061|<button type="primary" size="small" modal="6">View</button>|
|[[:results:exp108|Vinblastine 0.2μM R03 exp108]]|0.054|<button type="primary" size="small" modal="7">View</button>|
|[[:results:exp106|UM131593 0.2μM R03 exp106]]|0.051|<button type="primary" size="small" modal="8">View</button>|
|[[:results:exp80|RO-3307 4.7μM R02 exp80]]|0.051|<button type="primary" size="small" modal="9">View</button>|
|[[:results:exp3|Actinomycin-D 0.001μM R00 exp3]]|0.119|<button type="primary" size="small" modal="10">View</button>|
|[[:results:exp2|5-Fluorouracil 20μM R00 exp2]]|0.111|<button type="primary" size="small" modal="11">View</button>|
|[[:results:exp19|Etoposide 1μM R00 exp19]]|0.109|<button type="primary" size="small" modal="12">View</button>|
|[[:results:exp126|GSK461364A 0.1μM R03 exp126]]|0.096|<button type="primary" size="small" modal="13">View</button>|
|[[:results:exp7|Bortezomib 0.05μM R00 exp7]]|0.092|<button type="primary" size="small" modal="14">View</button>|
|[[:results:exp17|DABN 20μM R00 exp17]]|0.083|<button type="primary" size="small" modal="15">View</button>|
|[[:results:exp456|Benzoate 20000μM R08 exp456]]|0.083|<button type="primary" size="small" modal="16">View</button>|
|[[:results:exp472|CI-1040 9.5μM R08 exp472]]|0.08|<button type="primary" size="small" modal="17">View</button>|
|[[:results:exp4|Actinomycin-D 0.01μM R00 exp4]]|0.074|<button type="primary" size="small" modal="18">View</button>|
|[[:results:exp478|Doxorubicin 0.02μM R08 exp478]]|0.074|<button type="primary" size="small" modal="19">View</button>|
|[[:results:exp199|Etoposide 0.3μM R05 exp199]]|0.07|<button type="primary" size="small" modal="20">View</button>|
|[[:results:exp459|Bleomycin 5μM R08 exp459]]|0.068|<button type="primary" size="small" modal="21">View</button>|
|[[:results:exp98|BI-6727 0.04μM R03 exp98]]|0.068|<button type="primary" size="small" modal="22">View</button>|
|[[:results:exp96|BI-2536 0.02μM R03 exp96]]|0.066|<button type="primary" size="small" modal="23">View</button>|
|[[:results:exp539|42°C R08 exp539]]|0.062|<button type="primary" size="small" modal="24">View</button>|
|[[:results:exp451|Atovaquone 15μM R08 exp451]]|0.056|<button type="primary" size="small" modal="25">View</button>|
|[[:results:exp448|Ammonium tetrathiomolybdate 10μM R08 exp448]]|0.054|<button type="primary" size="small" modal="26">View</button>|
</modal>


<modal id="1" size="lg" title="MLN-4924 2μM R00 exp22  vs  Pimelic-diphenylamide-106 5μM R00 exp28">
{{:chemogenomics:comparison_plots:exp22_vs_exp28.png?nolink |}}
</modal>

<modal id="2" size="lg" title="MLN-4924 2μM R00 exp22  vs  THZ1 0.06μM R08 exp531">
{{:chemogenomics:comparison_plots:exp22_vs_exp531.png?nolink |}}
</modal>

<modal id="3" size="lg" title="MLN-4924 2μM R00 exp22  vs  Rotenone 20μM R00 exp34">
{{:chemogenomics:comparison_plots:exp22_vs_exp34.png?nolink |}}
</modal>

<modal id="4" size="lg" title="MLN-4924 2μM R00 exp22  vs  SNS-032 15μM R08 exp443">
{{:chemogenomics:comparison_plots:exp22_vs_exp443.png?nolink |}}
</modal>

<modal id="5" size="lg" title="MLN-4924 2μM R00 exp22  vs  PU-H71 1μM R08 exp515">
{{:chemogenomics:comparison_plots:exp22_vs_exp515.png?nolink |}}
</modal>

<modal id="6" size="lg" title="MLN-4924 2μM R00 exp22  vs  Mitomycin-C 0.06μM R08 exp503">
{{:chemogenomics:comparison_plots:exp22_vs_exp503.png?nolink |}}
</modal>

<modal id="7" size="lg" title="MLN-4924 2μM R00 exp22  vs  Vinblastine 0.2μM R03 exp108">
{{:chemogenomics:comparison_plots:exp108_vs_exp22.png?nolink |}}
</modal>

<modal id="8" size="lg" title="MLN-4924 2μM R00 exp22  vs  UM131593 0.2μM R03 exp106">
{{:chemogenomics:comparison_plots:exp106_vs_exp22.png?nolink |}}
</modal>

<modal id="9" size="lg" title="MLN-4924 2μM R00 exp22  vs  RO-3307 4.7μM R02 exp80">
{{:chemogenomics:comparison_plots:exp22_vs_exp80.png?nolink |}}
</modal>

<modal id="10" size="lg" title="Actinomycin-D 0.001μM R00 exp3  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp22_vs_exp3.png?nolink |}}
</modal>

<modal id="11" size="lg" title="5-Fluorouracil 20μM R00 exp2  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp2_vs_exp22.png?nolink |}}
</modal>

<modal id="12" size="lg" title="Etoposide 1μM R00 exp19  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp19_vs_exp22.png?nolink |}}
</modal>

<modal id="13" size="lg" title="GSK461364A 0.1μM R03 exp126  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp126_vs_exp22.png?nolink |}}
</modal>

<modal id="14" size="lg" title="Bortezomib 0.05μM R00 exp7  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp22_vs_exp7.png?nolink |}}
</modal>

<modal id="15" size="lg" title="DABN 20μM R00 exp17  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp17_vs_exp22.png?nolink |}}
</modal>

<modal id="16" size="lg" title="Benzoate 20000μM R08 exp456  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp22_vs_exp456.png?nolink |}}
</modal>

<modal id="17" size="lg" title="CI-1040 9.5μM R08 exp472  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp22_vs_exp472.png?nolink |}}
</modal>

<modal id="18" 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="19" size="lg" title="Doxorubicin 0.02μM R08 exp478  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp22_vs_exp478.png?nolink |}}
</modal>

<modal id="20" size="lg" title="Etoposide 0.3μM R05 exp199  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp199_vs_exp22.png?nolink |}}
</modal>

<modal id="21" size="lg" title="Bleomycin 5μM R08 exp459  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp22_vs_exp459.png?nolink |}}
</modal>

<modal id="22" size="lg" title="BI-6727 0.04μM R03 exp98  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp22_vs_exp98.png?nolink |}}
</modal>

<modal id="23" size="lg" title="BI-2536 0.02μM R03 exp96  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp22_vs_exp96.png?nolink |}}
</modal>

<modal id="24" size="lg" title="42°C R08 exp539  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp22_vs_exp539.png?nolink |}}
</modal>

<modal id="25" size="lg" title="Atovaquone 15μM R08 exp451  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp22_vs_exp451.png?nolink |}}
</modal>

<modal id="26" size="lg" title="Ammonium tetrathiomolybdate 10μM R08 exp448  vs  MLN-4924 2μM R00 exp22">
{{:chemogenomics:comparison_plots:exp22_vs_exp448.png?nolink |}}
</modal>



<modal id="modal_go_sensitive" size="lg" title="Top 30 sensitive GO terms">
^GO Term^Fold Change^Genes^
|catalytic activity, acting on a nucleic acid|8.61|SLFN11,PRIM1,POLE,DDX3X,CNOT2,POLR2L,WAPL,POLR2I,EXOSC1|
</modal>
<modal id="modal_go_resistant" size="lg" title="Top 30 resistant GO terms">
^GO Term^Fold Change^Genes^
|RNA polymerase III type 2 promoter sequence-specific DNA binding|368.47|RPTOR,MTOR|
|RNA polymerase III general transcription initiation factor binding|368.47|RPTOR,MTOR|
|5S rDNA binding|368.47|RPTOR,MTOR|
|regulation of pentose-phosphate shunt|276.35|TP53,RPTOR,MTOR|
|positive regulation of DNA damage checkpoint|276.35|TTI1,TTI2|
|regulation of NADP metabolic process|236.87|TP53,RPTOR,MTOR|
|TOR complex|165.81|RPTOR,TTI1,MTOR|
|rRNA transcription|75.37|TP53,GTF3A,GTF3C3|
|transcription by RNA polymerase III|72.72|GTF3A,GTF3C3,POLR3B,POLR3H,TBP|
|general transcription initiation factor binding|41.71|TP53,RPTOR,TBP,MTOR|
|cellular response to starvation|16.26|TP53,CDKN1A,RPTOR,MTOR,PIK3R4|
|transferase complex, transferring phosphorus-containing groups|11.72|CDKN1A,ENY2,POLR3B,POLR3H,TBP,PIK3R4|
|cellular response to external stimulus|10.17|TP53,BAK1,CDKN1A,RPTOR,MTOR,PIK3R4|
|DNA-templated transcription|9.29|TP53,PAX5,ENY2,GTF3A,GTF3C3,POLR3B,POLR3H,TBP|
|RNA biosynthetic process|9.06|TP53,PAX5,ENY2,GTF3A,GTF3C3,POLR3B,POLR3H,TBP|
|heterocycle biosynthetic process|6.09|TP53,GMPPB,PAX5,ENY2,GTF3A,GTF3C3,POLR3B,POLR3H,TBP,MTOR|
|nucleobase-containing compound biosynthetic process|5.98|TP53,GMPPB,PAX5,ENY2,GTF3A,GTF3C3,POLR3B,POLR3H,TBP|
|intracellular protein-containing complex|5.68|RTCB,ENY2,RPTOR,TTI1,MEAF6,POLR3B,POLR3H,TBP,MTOR|
|aromatic compound biosynthetic process|5.44|TP53,GMPPB,PAX5,ENY2,GTF3A,GTF3C3,POLR3B,POLR3H,TBP|
</modal>