THZ531 0.11μM R07 exp409 [The Human Chemical-Genetic Interaction Map Project]

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====== THZ531 0.11μM R07 exp409 ======
==== 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>**: 110nM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 6.3
    * **<color #00a2e8>Numbers of reads</color>**: 21370562


==== 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^
|13/3|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/THZ531_0.11uM_Round-7_exp409.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="default" size="sm" modal="modal_go_resistant">View</button>|
<modal id='ScorePlot' size='lg' title='THZ531 0.11μM R07 exp409'>
{{:chemogenomics:cranks_plots:exp409.png?nolink}}
</modal>


<modal id="modal_hits" size="sm" title="Top 30 S/R Genes">
^Gene^CRANKS Score^FDR^
|[[:human_genes:A:ABCG2|ABCG2]]|-5.32|<0.01|
|[[:human_genes:F:FAM58A|FAM58A]]|-3.90|<0.01|
|[[:human_genes:T:TCF4|TCF4]]|-3.66|<0.01|
|[[:human_genes:P:PBRM1|PBRM1]]|-3.48|<0.01|
|[[:human_genes:Z:ZBTB1|ZBTB1]]|-3.14|<0.01|
|[[:human_genes:F:FKBP8|FKBP8]]|-2.98|<0.01|
|[[:human_genes:A:ARID3A|ARID3A]]|-2.84|0.03|
|[[:human_genes:F:FBXO11|FBXO11]]|-2.80|<0.01|
|[[:human_genes:T:TMEM30A|TMEM30A]]|-2.79|<0.01|
|[[:human_genes:C:CDK10|CDK10]]|-2.73|0.01|
|[[:human_genes:W:WSB1|WSB1]]|-2.65|0.03|
|[[:human_genes:I:INTS12|INTS12]]|-2.58|0.02|
|[[:human_genes:D:DKC1|DKC1]]|-2.56|0.32|
|[[:human_genes:E:ENO1|ENO1]]|-2.50|0.05|
|[[:human_genes:S:SLC5A3|SLC5A3]]|-2.44|0.04|
|[[:human_genes:P:PARK7|PARK7]]|-2.36|0.05|
|[[:human_genes:S:SLC39A10|SLC39A10]]|-2.35|0.05|
|[[:human_genes:P:PRDM15|PRDM15]]|-2.35|0.05|
|[[:human_genes:H:HPRT1|HPRT1]]|-2.34|0.10|
|[[:human_genes:M:MCTS1|MCTS1]]|-2.33|0.06|
|[[:human_genes:U:UPF3B|UPF3B]]|-2.29|0.07|
|[[:human_genes:B:BACH2|BACH2]]|-2.28|0.11|
|[[:human_genes:E:ELF2|ELF2]]|-2.23|0.09|
|[[:human_genes:V:VCPIP1|VCPIP1]]|-2.19|0.11|
|[[:human_genes:S:SP3|SP3]]|-2.16|0.16|
|[[:human_genes:Z:ZNF608|ZNF608]]|-2.16|0.11|
|[[:human_genes:S:SP2|SP2]]|-2.16|0.11|
|[[:human_genes:A:ATP8B2|ATP8B2]]|-2.15|0.23|
|[[:human_genes:N:NUCB2|NUCB2]]|-2.15|0.11|
|[[:human_genes:Z:ZNF714|ZNF714]]|-2.15|0.11|
|[[:human_genes:S:SETD1B|SETD1B]]|2.06|0.37|
|[[:human_genes:T:TCEB1|TCEB1]]|2.06|0.25|
|[[:human_genes:A:ANKRD55|ANKRD55]]|2.08|0.28|
|[[:human_genes:L:LRRC63|LRRC63]]|2.08|0.65|
|[[:human_genes:S:SLC47A1|SLC47A1]]|2.10|0.22|
|[[:human_genes:I:INO80E|INO80E]]|2.10|0.26|
|[[:human_genes:F:FNDC8|FNDC8]]|2.12|0.25|
|[[:human_genes:M:MTF1|MTF1]]|2.12|0.25|
|[[:human_genes:F:FAM204A|FAM204A]]|2.13|0.20|
|[[:human_genes:P:PSMB4|PSMB4]]|2.13|0.20|
|[[:human_genes:N:NKAIN2|NKAIN2]]|2.14|0.20|
|[[:human_genes:S:SNRNP70|SNRNP70]]|2.15|0.25|
|[[:human_genes:T:TFPT|TFPT]]|2.16|0.31|
|[[:human_genes:I:ING1|ING1]]|2.17|0.20|
|[[:human_genes:S:SEMG2|SEMG2]]|2.27|0.20|
|[[:human_genes:U:UBE4B|UBE4B]]|2.32|0.10|
|[[:human_genes:K:KPTN|KPTN]]|2.33|0.10|
|[[:human_genes:M:MBTD1|MBTD1]]|2.37|0.10|
|[[:human_genes:V:VCP|VCP]]|2.38|0.15|
|[[:human_genes:S:SMC2|SMC2]]|2.38|0.22|
|[[:human_genes:T:TRIM52|TRIM52]]|2.44|0.33|
|[[:human_genes:E:ELAVL3|ELAVL3]]|2.45|0.08|
|[[:human_genes:C:CD68|CD68]]|2.46|0.25|
|[[:human_genes:C:CREB1|CREB1]]|2.47|0.08|
|[[:human_genes:T:TSPYL1|TSPYL1]]|2.65|0.10|
|[[:human_genes:M:MGA|MGA]]|2.72|0.04|
|[[:human_genes:K:KIAA0947|KIAA0947]]|2.77|0.06|
|[[:human_genes:C:CDC5L|CDC5L]]|2.83|0.10|
|[[:human_genes:S:SOX4|SOX4]]|3.45|<0.01|
|[[:human_genes:B:BEND3|BEND3]]|3.47|<0.01|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp444|THZ531 0.225μM R08 exp444]]|0.115|<button type="primary" size="small" modal="1">View</button>|
|[[:results:exp410|THZ531 0.11 to 0.125μM on day4 R07 exp410]]|0.288|<button type="primary" size="small" modal="2">View</button>|
|[[:results:exp413|THZ531 0.11 to 0.175μM on day4 R07 exp413]]|0.271|<button type="primary" size="small" modal="3">View</button>|
|[[:results:exp412|THZ531 0.11 to 0.125 to 0.35μM on day4 then day6 R07 exp412]]|0.259|<button type="primary" size="small" modal="4">View</button>|
</modal>


<modal id="1" size="lg" title="THZ531 0.11μM R07 exp409  vs  THZ531 0.225μM R08 exp444">
{{:chemogenomics:comparison_plots:exp409_vs_exp444.png?nolink |}}
</modal>

<modal id="2" size="lg" title="THZ531 0.11 to 0.125μM on day4 R07 exp410  vs  THZ531 0.11μM R07 exp409">
{{:chemogenomics:comparison_plots:exp409_vs_exp410.png?nolink |}}
</modal>

<modal id="3" 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="4" size="lg" title="THZ531 0.11 to 0.125 to 0.35μM on day4 then day6 R07 exp412  vs  THZ531 0.11μM R07 exp409">
{{:chemogenomics:comparison_plots:exp409_vs_exp412.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">No GO term hits below threshold. (FDR <0.05)</modal>