THZ531 0.11 to 0.175μM on day4 R07 exp413 [The Human Chemical-Genetic Interaction Map Project]

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====== THZ531 0.11 to 0.175μM on day4 R07 exp413 ======
==== Mechanism of Action ====
Inhibits CDK12 and CDK13, forms covalent adduct, more selective analog of THZ1, blocks phosphorylation of the C-terminal domain of RNA polymerase II
  * **<color #00a2e8>Class / Subclass 1:</color>** Gene Regulation / Transcription Inhibitor
  * **<color #00a2e8>Class / Subclass 2:</color>** Signal Transduction / Kinase Inhibitor



==== Technical Notes ====
<accordion collapsed='true'>
<panel title='Compound References' collapsed='true'>
    * **<color #00a2e8>PubChem Name:</color>** %%(E)-N-[4-[(3R)-3-[[5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]piperidine-1-carbonyl]phenyl]-4-(dimethylamino)but-2-enamide%%
    * **<color #00a2e8>Synonyms:</color>** N/A
    * **<color #00a2e8>CAS #:</color>** 1702809-17-3
    * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/118025540|118025540]]
    * **<color #00a2e8>IUPAC:</color>** %%(E)-N-[4-[(3R)-3-[[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]piperidine-1-carbonyl]phenyl]-4-(dimethylamino)but-2-enamide%%
    * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C30H32ClN7O2/c1-37(2)15-6-10-27(39)34-21-13-11-20(12-14-21)29(40)38-16-5-7-22(19-38)35-30-33-18-25(31)28(36-30)24-17-32-26-9-4-3-8-23(24)26/h3-4,6,8-14,17-18,22,32H,5,7,15-16,19H2,1-2H3,(H,34,39)(H,33,35,36)/b10-6+/t22-/m1/s1
    * **<color #00a2e8>INCHI Key:</color>** RUBYHLPRZRMTJO-MOVYNIQHSA-N
    * **<color #00a2e8>Molecular Weight:</color>** 558.1
    * **<color #00a2e8>Canonical SMILES:</color>** CN(C)CC=CC(=O)NC1=CC=C(C=C1)C(=O)N2CCCC(C2)NC3=NC=C(C(=N3)C4=CNC5=CC=CC=C54)Cl
    * **<color #00a2e8>Isomeric SMILES:</color>** CN(C)C/C=C/C(=O)NC1=CC=C(C=C1)C(=O)N2CCC[C@H](C2)NC3=NC=C(C(=N3)C4=CNC5=CC=CC=C54)Cl
    * **<color #00a2e8>Molecular Formula:</color>** C30H32ClN7O2
{{:chemogenomics:structures:chem-0246.svg?nolink}}
</panel>


<panel title='Compound Supplier' collapsed='true'>
    * **<color #00a2e8>Supplier Name:</color>** Med Chem Express
    * **<color #00a2e8>Catalog #:</color>** HY-103618
    * **<color #00a2e8>Lot #:</color>** 28264
</panel>


<panel title='Compound Characterization' collapsed='true'>
    * **<color #00a2e8>HRMS (ESI-TOF) m/z:</color>** (M+H)+ Calcd for C30H32ClN7O2 558.23788; found 558.23943
</panel>


<panel title='Dose Response Curve' collapsed='true'>
    * **<color #00a2e8>Platform ID:</color>** THZ531
    * **<color #00a2e8>Min:</color>** -7.6335; **<color #00a2e8>Max:</color>** 95.3893
{{:chemogenomics:dose_response:dr_452.png?nolink&500 |}}
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|< 300px 100px 200px >|
^ IC   ^ Concentration (µM) ^
| IC10  |N/A    |
| IC20  |0.0546    |
| IC30  |0.0716    |
| IC40  |0.0910    |
| IC50  |0.1150    |
| IC60  |N/A    |
| IC70  |N/A    |
| IC80  |N/A    |
| IC90  |N/A    |
\\ 
</panel>
</accordion>
==== Screen Summary ====
    * **<color #00a2e8>Round</color>**: 07
    * **<color #00a2e8>Dose</color>**: 0.11-0.175µM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 5.8
    * **<color #00a2e8>Numbers of reads</color>**: 15770666


==== 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^
|15/19|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/THZ531_0.11-0.175day4uM_Round-7_exp413.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='THZ531 0.11 to 0.175μM on day4 R07 exp413'>
{{:chemogenomics:cranks_plots:exp413.png?nolink}}
</modal>


<modal id="modal_hits" size="sm" title="Top 30 S/R Genes">
^Gene^CRANKS Score^FDR^
|[[:human_genes:A:ABCG2|ABCG2]]|-4.88|<0.01|
|[[:human_genes:T:TCF4|TCF4]]|-4.12|<0.01|
|[[:human_genes:Z:ZBTB1|ZBTB1]]|-3.65|<0.01|
|[[:human_genes:Z:ZBTB11|ZBTB11]]|-3.30|<0.01|
|[[:human_genes:F:FAM58A|FAM58A]]|-3.24|<0.01|
|[[:human_genes:P:PBRM1|PBRM1]]|-3.18|<0.01|
|[[:human_genes:T:TMEM30A|TMEM30A]]|-3.02|<0.01|
|[[:human_genes:S:SLC5A3|SLC5A3]]|-2.97|<0.01|
|[[:human_genes:C:CDK10|CDK10]]|-2.92|<0.01|
|[[:human_genes:R:RUVBL1|RUVBL1]]|-2.85|0.17|
|[[:human_genes:B:BCOR|BCOR]]|-2.75|<0.01|
|[[:human_genes:A:ALG9|ALG9]]|-2.65|0.01|
|[[:human_genes:A:ATP8B2|ATP8B2]]|-2.58|0.06|
|[[:human_genes:F:FKBP8|FKBP8]]|-2.57|0.02|
|[[:human_genes:A:ARID3A|ARID3A]]|-2.55|0.07|
|[[:human_genes:P:PEX7|PEX7]]|-2.52|0.02|
|[[:human_genes:E:ELF2|ELF2]]|-2.51|0.02|
|[[:human_genes:C:CYP20A1|CYP20A1]]|-2.48|0.03|
|[[:human_genes:S:SUPT20HL1|SUPT20HL1]]|-2.44|0.06|
|[[:human_genes:F:FBXO11|FBXO11]]|-2.35|0.05|
|[[:human_genes:C:CBX5|CBX5]]|-2.35|0.05|
|[[:human_genes:R:RPRD1B|RPRD1B]]|-2.33|0.06|
|[[:human_genes:P:PPP2R2A|PPP2R2A]]|-2.32|0.06|
|[[:human_genes:C:CUL4A|CUL4A]]|-2.31|0.09|
|[[:human_genes:C:CCNK|CCNK]]|-2.29|0.06|
|[[:human_genes:W:WSB1|WSB1]]|-2.27|0.09|
|[[:human_genes:M:MOCS3|MOCS3]]|-2.26|0.09|
|[[:human_genes:R:RNASEH2A|RNASEH2A]]|-2.26|0.09|
|[[:human_genes:P:PRDM10|PRDM10]]|-2.25|0.07|
|[[:human_genes:W:WDR20|WDR20]]|-2.25|0.07|
|[[:human_genes:H:HDAC2|HDAC2]]|2.25|0.08|
|[[:human_genes:Z:ZNF83|ZNF83]]|2.25|0.08|
|[[:human_genes:U:UCHL5|UCHL5]]|2.33|0.05|
|[[:human_genes:R:RPL5|RPL5]]|2.33|0.14|
|[[:human_genes:T:TTC37|TTC37]]|2.33|0.14|
|[[:human_genes:B:BRMS1|BRMS1]]|2.36|0.14|
|[[:human_genes:L:LEMD3|LEMD3]]|2.37|0.08|
|[[:human_genes:E:EIF4A1|EIF4A1]]|2.38|0.08|
|[[:human_genes:S:SETD1B|SETD1B]]|2.38|0.13|
|[[:human_genes:C:CREB1|CREB1]]|2.42|0.03|
|[[:human_genes:N:NFRKB|NFRKB]]|2.44|0.03|
|[[:human_genes:N:NBEAL2|NBEAL2]]|2.46|0.03|
|[[:human_genes:K:KPTN|KPTN]]|2.49|0.03|
|[[:human_genes:P:PSMA7|PSMA7]]|2.52|0.14|
|[[:human_genes:C:C19orf53|C19orf53]]|2.64|0.03|
|[[:human_genes:R:RRP15|RRP15]]|2.68|<0.01|
|[[:human_genes:I:IPO5|IPO5]]|2.68|<0.01|
|[[:human_genes:D:DEGS1|DEGS1]]|2.70|<0.01|
|[[:human_genes:Z:ZFY|ZFY]]|2.75|<0.01|
|[[:human_genes:T:TMSB15B|TMSB15B]]|2.77|0.26|
|[[:human_genes:M:MBTD1|MBTD1]]|2.80|<0.01|
|[[:human_genes:T:TFPT|TFPT]]|2.83|0.03|
|[[:human_genes:B:BRD1|BRD1]]|2.83|<0.01|
|[[:human_genes:I:ING1|ING1]]|3.05|<0.01|
|[[:human_genes:F:FBXL20|FBXL20]]|3.07|<0.01|
|[[:human_genes:U:UBE4B|UBE4B]]|3.28|<0.01|
|[[:human_genes:M:MGA|MGA]]|3.44|<0.01|
|[[:human_genes:I:INO80E|INO80E]]|3.56|<0.01|
|[[:human_genes:S:SOX4|SOX4]]|4.76|<0.01|
|[[:human_genes:B:BEND3|BEND3]]|6.37|<0.01|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp409|THZ531 0.11μM R07 exp409]]|0.271|<button type="primary" size="small" modal="1">View</button>|
|[[:results:exp444|THZ531 0.225μM R08 exp444]]|0.186|<button type="primary" size="small" modal="2">View</button>|
|[[:results:exp412|THZ531 0.11 to 0.125 to 0.35μM on day4 then day6 R07 exp412]]|0.329|<button type="primary" size="small" modal="3">View</button>|
|[[:results:exp410|THZ531 0.11 to 0.125μM on day4 R07 exp410]]|0.309|<button type="primary" size="small" modal="4">View</button>|
|[[:results:exp102|Nifuroxazide 5μM R03 exp102]]|0.08|<button type="primary" size="small" modal="5">View</button>|
|[[:results:exp505|ML-792 0.2μM R08 exp505]]|0.076|<button type="primary" size="small" modal="6">View</button>|
|[[:results:exp21|MLN-4924 0.2μM R00 exp21]]|0.068|<button type="primary" size="small" modal="7">View</button>|
</modal>


<modal id="1" size="lg" title="THZ531 0.11 to 0.175μM on day4 R07 exp413  vs  THZ531 0.11μM R07 exp409">
{{:chemogenomics:comparison_plots:exp409_vs_exp413.png?nolink |}}
</modal>

<modal id="2" size="lg" title="THZ531 0.11 to 0.175μM on day4 R07 exp413  vs  THZ531 0.225μM R08 exp444">
{{:chemogenomics:comparison_plots:exp413_vs_exp444.png?nolink |}}
</modal>

<modal id="3" size="lg" title="THZ531 0.11 to 0.125 to 0.35μM on day4 then day6 R07 exp412  vs  THZ531 0.11 to 0.175μM on day4 R07 exp413">
{{:chemogenomics:comparison_plots:exp412_vs_exp413.png?nolink |}}
</modal>

<modal id="4" size="lg" title="THZ531 0.11 to 0.125μM on day4 R07 exp410  vs  THZ531 0.11 to 0.175μM on day4 R07 exp413">
{{:chemogenomics:comparison_plots:exp410_vs_exp413.png?nolink |}}
</modal>

<modal id="5" size="lg" title="Nifuroxazide 5μM R03 exp102  vs  THZ531 0.11 to 0.175μM on day4 R07 exp413">
{{:chemogenomics:comparison_plots:exp102_vs_exp413.png?nolink |}}
</modal>

<modal id="6" size="lg" title="ML-792 0.2μM R08 exp505  vs  THZ531 0.11 to 0.175μM on day4 R07 exp413">
{{:chemogenomics:comparison_plots:exp413_vs_exp505.png?nolink |}}
</modal>

<modal id="7" size="lg" title="MLN-4924 0.2μM R00 exp21  vs  THZ531 0.11 to 0.175μM on day4 R07 exp413">
{{:chemogenomics:comparison_plots:exp21_vs_exp413.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^
|Ino80 complex|170.04|INO80E,TFPT,NFRKB,UCHL5|
|positive regulation of telomere maintenance in response to DNA damage|170.04|INO80E,TFPT,NFRKB,UCHL5|
|regulation of telomere maintenance in response to DNA damage|130.03|INO80E,TFPT,NFRKB,UCHL5|
|regulation of DNA strand elongation|110.53|TFPT,NFRKB,UCHL5|
|INO80-type complex|92.11|INO80E,TFPT,NFRKB,UCHL5|
|Sin3 complex|78.95|ING1,BRMS1,HDAC2|
|Sin3-type complex|78.95|ING1,BRMS1,HDAC2|
|negative regulation of stem cell population maintenance|69.08|ING1,BRMS1,HDAC2|
|positive regulation of telomere maintenance|32.99|INO80E,TFPT,NFRKB,UCHL5|
|SWI/SNF superfamily-type complex|24.84|INO80E,TFPT,NFRKB,HDAC2|
|regulation of embryonic development|24.84|INO80E,TFPT,NFRKB,UCHL5|
|negative regulation of transforming growth factor beta receptor signaling pathway|24.56|ING1,LEMD3,BRMS1,HDAC2|
|telomere maintenance|24.29|INO80E,TFPT,NFRKB,UCHL5|
|positive regulation of DNA repair|22.65|INO80E,TFPT,MBTD1,NFRKB,UCHL5|
|ATPase complex|19.88|INO80E,TFPT,NFRKB,UCHL5,HDAC2|
|nuclear chromosome|17.66|INO80E,ING1,TFPT,NFRKB,BRMS1,UCHL5,HDAC2|
|chromatin remodeling|7.84|BEND3,INO80E,BRD1,TFPT,NFRKB,SETD1B,UCHL5,HDAC2|
|chromatin organization|7.04|BEND3,INO80E,BRD1,TFPT,MBTD1,NFRKB,SETD1B,UCHL5,HDAC2|
|protein-DNA complex organization|6.34|BEND3,INO80E,BRD1,TFPT,MBTD1,NFRKB,SETD1B,UCHL5,HDAC2|
</modal>