Nutlin-3A 1.6μM R06 exp294 [The Human Chemical-Genetic Interaction Map Project]

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====== Nutlin-3A 1.6μM R06 exp294 ======
==== Mechanism of Action ====
Inhibits p53-MDM2 interaction
  * **<color #00a2e8>Class / Subclass 1:</color>** Proteostasis / E3 ubiquitin ligase inhibitor
  * **<color #00a2e8>Class / Subclass 2:</color>** Signal Transduction / Apoptosis Activator



==== Technical Notes ====
<accordion collapsed='true'>
<panel title='Compound References' collapsed='true'>
    * **<color #00a2e8>PubChem Name:</color>** %%Nutlin-3A%%
    * **<color #00a2e8>Synonyms:</color>** Nutlin-3a chiral
    * **<color #00a2e8>CAS #:</color>** 675576-98-4
    * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/11433190|11433190]]
    * **<color #00a2e8>IUPAC:</color>** %%4-[(4S,5R)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one%%
    * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C30H30Cl2N4O4/c1-18(2)40-25-16-23(39-3)12-13-24(25)29-34-27(19-4-8-21(31)9-5-19)28(20-6-10-22(32)11-7-20)36(29)30(38)35-15-14-33-26(37)17-35/h4-13,16,18,27-28H,14-15,17H2,1-3H3,(H,33,37)/t27-,28+/m0/s1
    * **<color #00a2e8>INCHI Key:</color>** BDUHCSBCVGXTJM-WUFINQPMSA-N
    * **<color #00a2e8>Molecular Weight:</color>** 581.5
    * **<color #00a2e8>Canonical SMILES:</color>** CC(C)OC1=C(C=CC(=C1)OC)C2=NC(C(N2C(=O)N3CCNC(=O)C3)C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl
    * **<color #00a2e8>Isomeric SMILES:</color>** CC(C)OC1=C(C=CC(=C1)OC)C2=N[C@H]([C@H](N2C(=O)N3CCNC(=O)C3)C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl
    * **<color #00a2e8>Molecular Formula:</color>** C30H30Cl2N4O4
{{:chemogenomics:structures:chem-0182.svg?nolink}}
</panel>


<panel title='Compound Supplier' collapsed='true'>
    * **<color #00a2e8>Supplier Name:</color>** Sigma-Aldrich
    * **<color #00a2e8>Catalog #:</color>** SML0580
    * **<color #00a2e8>Lot #:</color>** N/A
</panel>


<panel title='Compound Characterization' collapsed='true'>
    * **<color #00a2e8>HRMS (ESI-TOF) m/z:</color>** (M+H)+ Calcd for C30H30Cl2N4O4 581.17169; found 581.17346
</panel>


<panel title='Dose Response Curve' collapsed='true'>
    * **<color #00a2e8>Platform ID:</color>** Nutlin-3A
    * **<color #00a2e8>Min:</color>** 0.0299; **<color #00a2e8>Max:</color>** 98.5570
{{:chemogenomics:dose_response:dr_329.png?nolink&500 |}}
\\ 
\\ 
\\ 
\\ 
|< 300px 100px 200px >|
^ IC   ^ Concentration (µM) ^
| IC10  |N/A    |
| IC20  |0.7608    |
| IC30  |1.0457    |
| IC40  |1.3571    |
| IC50  |1.7238    |
| IC60  |N/A    |
| IC70  |N/A    |
| IC80  |N/A    |
| IC90  |N/A    |
\\ 
</panel>
</accordion>
==== Screen Summary ====
    * **<color #00a2e8>Round</color>**: 06
    * **<color #00a2e8>Dose</color>**: 1.6µM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 2.3
    * **<color #00a2e8>Numbers of reads</color>**: 29565806


==== 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^
|15/64|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Nutlin-3A_1.6uM_Round-6_exp294.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='Nutlin-3A 1.6μM R06 exp294'>
{{:chemogenomics:cranks_plots:exp294.png?nolink}}
</modal>


<modal id="modal_hits" size="sm" title="Top 30 S/R Genes">
^Gene^CRANKS Score^FDR^
|[[:human_genes:P:PSME3|PSME3]]|-3.34|<0.01|
|[[:human_genes:Q:QRICH1|QRICH1]]|-3.16|0.01|
|[[:human_genes:S:SMARCAL1|SMARCAL1]]|-2.91|<0.01|
|[[:human_genes:T:TCF4|TCF4]]|-2.90|<0.01|
|[[:human_genes:P:POLQ|POLQ]]|-2.89|<0.01|
|[[:human_genes:P:PPM1D|PPM1D]]|-2.88|0.01|
|[[:human_genes:P:PPIL1|PPIL1]]|-2.79|0.02|
|[[:human_genes:A:ATRX|ATRX]]|-2.77|0.01|
|[[:human_genes:M:MDM4|MDM4]]|-2.75|0.02|
|[[:human_genes:D:DCLRE1B|DCLRE1B]]|-2.75|0.02|
|[[:human_genes:O:OTUB1|OTUB1]]|-2.75|0.02|
|[[:human_genes:S:SEPHS1|SEPHS1]]|-2.72|0.01|
|[[:human_genes:N:NPRL2|NPRL2]]|-2.61|0.03|
|[[:human_genes:S:SOX4|SOX4]]|-2.53|0.08|
|[[:human_genes:L:LEF1|LEF1]]|-2.52|0.03|
|[[:human_genes:G:GALNT7|GALNT7]]|-2.46|0.06|
|[[:human_genes:H:HELQ|HELQ]]|-2.42|0.04|
|[[:human_genes:E:EIF5B|EIF5B]]|-2.38|0.52|
|[[:human_genes:M:MSI2|MSI2]]|-2.36|0.05|
|[[:human_genes:P:PVRL2|PVRL2]]|-2.36|0.05|
|[[:human_genes:M:MRGBP|MRGBP]]|-2.31|0.16|
|[[:human_genes:G:GEN1|GEN1]]|-2.30|0.07|
|[[:human_genes:K:KIAA1524|KIAA1524]]|-2.29|0.07|
|[[:human_genes:P:PPP2R5D|PPP2R5D]]|-2.28|0.07|
|[[:human_genes:R:RPS17L|RPS17L]]|-2.26|0.29|
|[[:human_genes:S:SMC2|SMC2]]|-2.25|0.29|
|[[:human_genes:S:SREK1|SREK1]]|-2.25|0.08|
|[[:human_genes:Y:YY1|YY1]]|-2.25|0.29|
|[[:human_genes:P:PLCH1|PLCH1]]|-2.24|0.08|
|[[:human_genes:A:ADRM1|ADRM1]]|-2.23|0.13|
|[[:human_genes:D:DUSP6|DUSP6]]|2.91|0.00|
|[[:human_genes:P:PML|PML]]|2.96|0.00|
|[[:human_genes:A:ASUN|ASUN]]|2.97|<0.01|
|[[:human_genes:B:BAK1|BAK1]]|3.12|0.00|
|[[:human_genes:I:INTS10|INTS10]]|3.12|0.00|
|[[:human_genes:Z:ZBTB7A|ZBTB7A]]|3.31|0.00|
|[[:human_genes:C:CKS2|CKS2]]|3.37|0.00|
|[[:human_genes:S:SRRD|SRRD]]|3.42|0.00|
|[[:human_genes:H:H2AFZ|H2AFZ]]|3.46|0.00|
|[[:human_genes:C:CCDC6|CCDC6]]|3.51|0.00|
|[[:human_genes:S:SLFN11|SLFN11]]|3.65|0.00|
|[[:human_genes:P:PRKRIR|PRKRIR]]|3.65|0.00|
|[[:human_genes:S:STRA13|STRA13]]|3.69|0.00|
|[[:human_genes:C:C19orf43|C19orf43]]|3.78|0.00|
|[[:human_genes:H:HSPA4|HSPA4]]|3.81|0.00|
|[[:human_genes:P:PGP|PGP]]|3.81|0.00|
|[[:human_genes:T:TOP3A|TOP3A]]|3.85|0.00|
|[[:human_genes:H:HSF1|HSF1]]|3.87|0.00|
|[[:human_genes:M:MUM1|MUM1]]|3.98|0.00|
|[[:human_genes:C:C19orf40|C19orf40]]|4.02|0.00|
|[[:human_genes:A:APITD1-CORT|APITD1-CORT]]|4.16|0.00|
|[[:human_genes:T:TRIP12|TRIP12]]|4.44|0.00|
|[[:human_genes:F:FBXO11|FBXO11]]|4.72|0.00|
|[[:human_genes:A:APITD1|APITD1]]|4.79|0.00|
|[[:human_genes:F:FANCM|FANCM]]|5.25|0.00|
|[[:human_genes:C:CHEK2|CHEK2]]|6.17|0.00|
|[[:human_genes:B:BLM|BLM]]|7.00|0.00|
|[[:human_genes:R:RMI1|RMI1]]|7.95|0.00|
|[[:human_genes:T:TP53|TP53]]|8.35|0.00|
|[[:human_genes:R:RMI2|RMI2]]|8.50|0.00|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp512|Olaparib 4μM R08 exp512]]|0.078|<button type="primary" size="small" modal="1">View</button>|
|[[:results:exp520|Rucaparib 6.5μM R08 exp520]]|0.071|<button type="primary" size="small" modal="2">View</button>|
|[[:results:exp517|Quercetin 20μM R08 exp517]]|0.07|<button type="primary" size="small" modal="3">View</button>|
|[[:results:exp78|Pterostilbene 16μM R02 exp78]]|0.067|<button type="primary" size="small" modal="4">View</button>|
|[[:results:exp299|Talazoparib 0.006μM R06 exp299]]|0.067|<button type="primary" size="small" modal="5">View</button>|
|[[:results:exp525|Sulforaphane 9μM R08 exp525]]|0.061|<button type="primary" size="small" modal="6">View</button>|
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|0.053|<button type="primary" size="small" modal="7">View</button>|
|[[:results:exp354|Diepoxybutane 3μM R07 exp354]]|0.125|<button type="primary" size="small" modal="8">View</button>|
|[[:results:exp116|AICAR 240μM R03 exp116]]|0.084|<button type="primary" size="small" modal="9">View</button>|
|[[:results:exp211|AICAR 240μM R05 exp211]]|0.074|<button type="primary" size="small" modal="10">View</button>|
|[[:results:exp440|Aphidicolin 0.4μM R08 exp440]]|0.07|<button type="primary" size="small" modal="11">View</button>|
|[[:results:exp360|Genistein 15μM R07 exp360]]|0.069|<button type="primary" size="small" modal="12">View</button>|
|[[:results:exp503|Mitomycin-C 0.06μM R08 exp503]]|0.063|<button type="primary" size="small" modal="13">View</button>|
|[[:results:exp485|GSK626616 14μM R08 exp485]]|0.061|<button type="primary" size="small" modal="14">View</button>|
|[[:results:exp468|CB-5083 0.4μM R08 exp468]]|0.058|<button type="primary" size="small" modal="15">View</button>|
|[[:results:exp67|BVD-523 15μM R02 exp67]]|0.057|<button type="primary" size="small" modal="16">View</button>|
|[[:results:exp456|Benzoate 20000μM R08 exp456]]|0.056|<button type="primary" size="small" modal="17">View</button>|
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|0.056|<button type="primary" size="small" modal="18">View</button>|
|[[:results:exp488|Hippuristanol 0.12μM R08 exp488]]|0.055|<button type="primary" size="small" modal="19">View</button>|
|[[:results:exp498|Lead acetate 2000μM R08 exp498 no dilution day6]]|0.055|<button type="primary" size="small" modal="20">View</button>|
|[[:results:exp134|MS023 2μM R03 exp134]]|0.054|<button type="primary" size="small" modal="21">View</button>|
|[[:results:exp217|Mdivi-1 15μM R05 exp217]]|0.054|<button type="primary" size="small" modal="22">View</button>|
|[[:results:exp451|Atovaquone 15μM R08 exp451]]|0.054|<button type="primary" size="small" modal="23">View</button>|
|[[:results:exp292|Menadione 5μM R06 exp292]]|0.053|<button type="primary" size="small" modal="24">View</button>|
|[[:results:exp343|Centrinone 0.5μM R07 exp343]]|0.052|<button type="primary" size="small" modal="25">View</button>|
|[[:results:exp312|2-Methoxyestradiol 0.55 to 1μM on day4 R07 exp312]]|0.051|<button type="primary" size="small" modal="26">View</button>|
|[[:results:exp264|Arsenate 40μM R06 exp264]]|0.051|<button type="primary" size="small" modal="27">View</button>|
</modal>


<modal id="1" size="lg" title="Nutlin-3A 1.6μM R06 exp294  vs  Olaparib 4μM R08 exp512">
{{:chemogenomics:comparison_plots:exp294_vs_exp512.png?nolink |}}
</modal>

<modal id="2" size="lg" title="Nutlin-3A 1.6μM R06 exp294  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp294_vs_exp520.png?nolink |}}
</modal>

<modal id="3" size="lg" title="Nutlin-3A 1.6μM R06 exp294  vs  Quercetin 20μM R08 exp517">
{{:chemogenomics:comparison_plots:exp294_vs_exp517.png?nolink |}}
</modal>

<modal id="4" size="lg" title="Nutlin-3A 1.6μM R06 exp294  vs  Pterostilbene 16μM R02 exp78">
{{:chemogenomics:comparison_plots:exp294_vs_exp78.png?nolink |}}
</modal>

<modal id="5" size="lg" title="Nutlin-3A 1.6μM R06 exp294  vs  Talazoparib 0.006μM R06 exp299">
{{:chemogenomics:comparison_plots:exp294_vs_exp299.png?nolink |}}
</modal>

<modal id="6" size="lg" title="Nutlin-3A 1.6μM R06 exp294  vs  Sulforaphane 9μM R08 exp525">
{{:chemogenomics:comparison_plots:exp294_vs_exp525.png?nolink |}}
</modal>

<modal id="7" size="lg" title="Nutlin-3A 1.6μM R06 exp294  vs  Trimetrexate 0.03μM R08 exp535">
{{:chemogenomics:comparison_plots:exp294_vs_exp535.png?nolink |}}
</modal>

<modal id="8" size="lg" title="Diepoxybutane 3μM R07 exp354  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp354.png?nolink |}}
</modal>

<modal id="9" size="lg" title="AICAR 240μM R03 exp116  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp116_vs_exp294.png?nolink |}}
</modal>

<modal id="10" size="lg" title="AICAR 240μM R05 exp211  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp211_vs_exp294.png?nolink |}}
</modal>

<modal id="11" size="lg" title="Aphidicolin 0.4μM R08 exp440  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp440.png?nolink |}}
</modal>

<modal id="12" size="lg" title="Genistein 15μM R07 exp360  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp360.png?nolink |}}
</modal>

<modal id="13" size="lg" title="Mitomycin-C 0.06μM R08 exp503  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp503.png?nolink |}}
</modal>

<modal id="14" size="lg" title="GSK626616 14μM R08 exp485  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp485.png?nolink |}}
</modal>

<modal id="15" size="lg" title="CB-5083 0.4μM R08 exp468  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp468.png?nolink |}}
</modal>

<modal id="16" size="lg" title="BVD-523 15μM R02 exp67  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp67.png?nolink |}}
</modal>

<modal id="17" size="lg" title="Benzoate 20000μM R08 exp456  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp456.png?nolink |}}
</modal>

<modal id="18" size="lg" title="Lead acetate 2000μM R08 exp497  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp497.png?nolink |}}
</modal>

<modal id="19" size="lg" title="Hippuristanol 0.12μM R08 exp488  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp488.png?nolink |}}
</modal>

<modal id="20" size="lg" title="Lead acetate 2000μM R08 exp498 no dilution day6  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp498.png?nolink |}}
</modal>

<modal id="21" size="lg" title="MS023 2μM R03 exp134  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp134_vs_exp294.png?nolink |}}
</modal>

<modal id="22" size="lg" title="Mdivi-1 15μM R05 exp217  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp217_vs_exp294.png?nolink |}}
</modal>

<modal id="23" size="lg" title="Atovaquone 15μM R08 exp451  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp451.png?nolink |}}
</modal>

<modal id="24" size="lg" title="Menadione 5μM R06 exp292  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp292_vs_exp294.png?nolink |}}
</modal>

<modal id="25" size="lg" title="Centrinone 0.5μM R07 exp343  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp343.png?nolink |}}
</modal>

<modal id="26" size="lg" title="2-Methoxyestradiol 0.55 to 1μM on day4 R07 exp312  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp294_vs_exp312.png?nolink |}}
</modal>

<modal id="27" size="lg" title="Arsenate 40μM R06 exp264  vs  Nutlin-3A 1.6μM R06 exp294">
{{:chemogenomics:comparison_plots:exp264_vs_exp294.png?nolink |}}
</modal>



<modal id="modal_go_sensitive" size="lg" title="Top 30 sensitive GO terms">
^GO Term^Fold Change^Genes^
|double-strand break repair via alternative nonhomologous end joining|381.03|POLQ,HELQ|
|double-strand break repair via nonhomologous end joining|54.43|SMARCAL1,POLQ,DCLRE1B,HELQ|
|telomere organization|22.64|SMARCAL1,ATRX,DCLRE1B,YY1|
|double-strand break repair|17.06|SMARCAL1,POLQ,DCLRE1B,HELQ,GEN1,YY1|
|catalytic activity, acting on DNA|14.47|SMARCAL1,POLQ,ATRX,DCLRE1B,HELQ,GEN1|
|regulation of DNA repair|14.15|POLQ,OTUB1,HELQ,MRGBP,YY1|
|DNA repair|9.71|SMARCAL1,POLQ,ATRX,DCLRE1B,OTUB1,HELQ,GEN1,YY1|
|chromosome organization|9.05|SMARCAL1,POLQ,ATRX,DCLRE1B,HELQ,SMC2,YY1|
|DNA damage response|7.99|SMARCAL1,POLQ,PPM1D,ATRX,MDM4,DCLRE1B,OTUB1,HELQ,GEN1,YY1|
|DNA metabolic process|7.98|SMARCAL1,POLQ,PPM1D,ATRX,DCLRE1B,OTUB1,LEF1,HELQ,GEN1,YY1|
</modal>
<modal id="modal_go_resistant" size="lg" title="Top 30 resistant GO terms">
^GO Term^Fold Change^Genes^
|RecQ family helicase-topoisomerase III complex|552.50|RMI2,RMI1,BLM|
|resolution of recombination intermediates|331.50|RMI2,RMI1,BLM|
|Fanconi anaemia nuclear complex|184.17|FANCM,CENPS,CENPX|
|resolution of meiotic recombination intermediates|147.33|RMI1,FANCM,CENPS,CENPX|
|response to gamma radiation|57.55|TP53,CHEK2,HSF1,BAK1,PML|
|DNA-templated DNA replication maintenance of fidelity|52.12|BLM,FANCM,CENPS,CENPX,SLFN11|
|replication fork processing|48.04|BLM,FANCM,CENPS,CENPX|
|recombinational repair|32.50|RMI2,RMI1,BLM,FANCM,TOP3A,SWSAP1,NSMCE4A|
|PML body|31.57|TP53,BLM,CHEK2,HSF1,TOP3A,PML|
|double-strand break repair via homologous recombination|28.58|RMI2,RMI1,BLM,FANCM,TOP3A,NSMCE4A|
|double-strand break repair|27.49|RMI2,TP53,RMI1,BLM,CHEK2,FANCM,TOP3A,ZBTB7A,SWSAP1,NSMCE4A|
|response to ionizing radiation|24.92|TP53,BLM,CHEK2,HSF1,BAK1,PML|
|DNA recombination|22.10|RMI2,RMI1,BLM,FANCM,CENPS,TOP3A,CENPX,SWSAP1,NSMCE4A|
|DNA replication|19.94|RMI2,RMI1,BLM,FANCM,CENPS,CENPX,SLFN11|
|DNA repair|17.60|RMI2,TP53,RMI1,BLM,CHEK2,FANCM,CENPS,TRIP12,PWWP3A,HSF1,TOP3A,CENPX,ZBTB7A,SWSAP1,NSMCE4A|
|DNA damage response|13.91|RMI2,TP53,RMI1,BLM,CHEK2,FANCM,CENPS,TRIP12,PWWP3A,HSF1,TOP3A,CENPX,SLFN11,ZBTB7A,BAK1,PML,SWSAP1,NSMCE4A|
|DNA metabolic process|12.35|RMI2,TP53,RMI1,BLM,CHEK2,FANCM,CENPS,TRIP12,PWWP3A,HSF1,TOP3A,CENPX,SLFN11,ZBTB7A,SWSAP1,NSMCE4A|
|nuclear body|7.50|RMI2,TP53,RMI1,BLM,CHEK2,TRIP12,HSF1,TOP3A,INTS13,PML,NSMCE4A|
|cell cycle process|6.95|TP53,RMI1,BLM,CHEK2,FANCM,CENPS,TOP3A,CENPX,CKS2,INTS13,PML|
</modal>