====== THZ531 0.225μM R08 exp444 ======
==== 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>**: 08
    * **<color #00a2e8>Dose</color>**: 225nM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 2.4
    * **<color #00a2e8>Numbers of reads</color>**: 14688483


==== 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^
|11/57|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/THZ531_0.225uM_Round-8_exp444.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 0.225μM R08 exp444'>
{{:chemogenomics:cranks_plots:exp444.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]]|-3.77|<0.01|
|[[:human_genes:C:CDK10|CDK10]]|-3.56|<0.01|
|[[:human_genes:Z:ZBTB1|ZBTB1]]|-3.30|<0.01|
|[[:human_genes:A:ATP8B2|ATP8B2]]|-3.11|0.01|
|[[:human_genes:D:DDX23|DDX23]]|-3.06|0.12|
|[[:human_genes:T:TMEM127|TMEM127]]|-2.90|<0.01|
|[[:human_genes:T:TMEM30A|TMEM30A]]|-2.82|<0.01|
|[[:human_genes:E:ENO1|ENO1]]|-2.82|0.07|
|[[:human_genes:I:ING5|ING5]]|-2.70|0.01|
|[[:human_genes:C:CNOT8|CNOT8]]|-2.70|0.01|
|[[:human_genes:M:MMGT1|MMGT1]]|-2.65|0.04|
|[[:human_genes:A:ALG9|ALG9]]|-2.65|0.02|
|[[:human_genes:C:CDK12|CDK12]]|-2.58|0.05|
|[[:human_genes:H:HDGFRP2|HDGFRP2]]|-2.46|0.07|
|[[:human_genes:Z:ZBTB11|ZBTB11]]|-2.44|0.07|
|[[:human_genes:R:RPRD1B|RPRD1B]]|-2.43|0.07|
|[[:human_genes:X:XPO5|XPO5]]|-2.43|0.10|
|[[:human_genes:M:METTL9|METTL9]]|-2.35|0.07|
|[[:human_genes:E:EMC2|EMC2]]|-2.34|0.07|
|[[:human_genes:A:AGPS|AGPS]]|-2.34|0.08|
|[[:human_genes:T:TSTD2|TSTD2]]|-2.32|0.07|
|[[:human_genes:S:SLC28A3|SLC28A3]]|-2.31|0.07|
|[[:human_genes:U:USF1|USF1]]|-2.26|0.07|
|[[:human_genes:S:SNX9|SNX9]]|-2.24|0.08|
|[[:human_genes:R:REC8|REC8]]|-2.23|0.12|
|[[:human_genes:M:MSL2|MSL2]]|-2.22|0.08|
|[[:human_genes:S:SLC5A3|SLC5A3]]|-2.22|0.08|
|[[:human_genes:P:PBRM1|PBRM1]]|-2.21|0.08|
|[[:human_genes:X:XPOT|XPOT]]|-2.21|0.12|
|[[:human_genes:U:UCHL5|UCHL5]]|2.88|<0.01|
|[[:human_genes:E:EIF4G1|EIF4G1]]|2.88|<0.01|
|[[:human_genes:B:BRD1|BRD1]]|2.89|<0.01|
|[[:human_genes:H:HEXIM1|HEXIM1]]|2.93|<0.01|
|[[:human_genes:B:BRMS1|BRMS1]]|2.96|<0.01|
|[[:human_genes:M:MIDN|MIDN]]|2.98|0.00|
|[[:human_genes:M:MBTD1|MBTD1]]|3.00|0.00|
|[[:human_genes:E:EIF3E|EIF3E]]|3.05|<0.01|
|[[:human_genes:E:EIF3G|EIF3G]]|3.08|<0.01|
|[[:human_genes:R:RCOR1|RCOR1]]|3.10|0.00|
|[[:human_genes:F:FAF2|FAF2]]|3.11|<0.01|
|[[:human_genes:D:DEGS1|DEGS1]]|3.14|0.00|
|[[:human_genes:M:MGA|MGA]]|3.31|0.00|
|[[:human_genes:A:ACSL4|ACSL4]]|3.32|0.00|
|[[:human_genes:N:NOB1|NOB1]]|3.40|0.00|
|[[:human_genes:T:TADA2A|TADA2A]]|3.47|0.00|
|[[:human_genes:M:MEMO1|MEMO1]]|3.54|0.00|
|[[:human_genes:S:SOX4|SOX4]]|3.55|0.00|
|[[:human_genes:C:C19orf53|C19orf53]]|3.56|0.00|
|[[:human_genes:F:FBXL20|FBXL20]]|3.67|0.00|
|[[:human_genes:U:UBE2Q1|UBE2Q1]]|3.68|0.00|
|[[:human_genes:Z:ZFY|ZFY]]|3.82|0.00|
|[[:human_genes:R:RPL5|RPL5]]|3.89|0.00|
|[[:human_genes:H:HEATR3|HEATR3]]|3.91|0.00|
|[[:human_genes:F:FAM60A|FAM60A]]|3.94|0.00|
|[[:human_genes:U:UBE4B|UBE4B]]|4.12|0.00|
|[[:human_genes:R:RPL11|RPL11]]|4.33|0.00|
|[[:human_genes:Z:ZBTB7A|ZBTB7A]]|4.68|0.00|
|[[:human_genes:E:EIF4A1|EIF4A1]]|4.95|0.00|
|[[:human_genes:B:BEND3|BEND3]]|8.10|0.00|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp412|THZ531 0.11 to 0.125 to 0.35μM on day4 then day6 R07 exp412]]|0.211|<button type="primary" size="small" modal="1">View</button>|
|[[:results:exp413|THZ531 0.11 to 0.175μM on day4 R07 exp413]]|0.186|<button type="primary" size="small" modal="2">View</button>|
|[[:results:exp410|THZ531 0.11 to 0.125μM on day4 R07 exp410]]|0.161|<button type="primary" size="small" modal="3">View</button>|
|[[:results:exp409|THZ531 0.11μM R07 exp409]]|0.115|<button type="primary" size="small" modal="4">View</button>|
|[[:results:exp505|ML-792 0.2μM R08 exp505]]|0.102|<button type="primary" size="small" modal="5">View</button>|
|[[:results:exp21|MLN-4924 0.2μM R00 exp21]]|0.099|<button type="primary" size="small" modal="6">View</button>|
|[[:results:exp102|Nifuroxazide 5μM R03 exp102]]|0.087|<button type="primary" size="small" modal="7">View</button>|
|[[:results:exp234|Ethanol 0.01 R05 exp234]]|0.06|<button type="primary" size="small" modal="8">View</button>|
|[[:results:exp3|Actinomycin-D 0.001μM R00 exp3]]|0.055|<button type="primary" size="small" modal="9">View</button>|
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|0.052|<button type="primary" size="small" modal="10">View</button>|
|[[:results:exp240|Pyridostatin 4μM R05 exp240]]|0.051|<button type="primary" size="small" modal="11">View</button>|
</modal>


<modal id="1" size="lg" title="THZ531 0.11 to 0.125 to 0.35μM on day4 then day6 R07 exp412  vs  THZ531 0.225μM R08 exp444">
{{:chemogenomics:comparison_plots:exp412_vs_exp444.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 0.125μM on day4 R07 exp410  vs  THZ531 0.225μM R08 exp444">
{{:chemogenomics:comparison_plots:exp410_vs_exp444.png?nolink |}}
</modal>

<modal id="4" 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="5" size="lg" title="ML-792 0.2μM R08 exp505  vs  THZ531 0.225μM R08 exp444">
{{:chemogenomics:comparison_plots:exp444_vs_exp505.png?nolink |}}
</modal>

<modal id="6" size="lg" title="MLN-4924 0.2μM R00 exp21  vs  THZ531 0.225μM R08 exp444">
{{:chemogenomics:comparison_plots:exp21_vs_exp444.png?nolink |}}
</modal>

<modal id="7" size="lg" title="Nifuroxazide 5μM R03 exp102  vs  THZ531 0.225μM R08 exp444">
{{:chemogenomics:comparison_plots:exp102_vs_exp444.png?nolink |}}
</modal>

<modal id="8" size="lg" title="Ethanol 0.01 R05 exp234  vs  THZ531 0.225μM R08 exp444">
{{:chemogenomics:comparison_plots:exp234_vs_exp444.png?nolink |}}
</modal>

<modal id="9" size="lg" title="Actinomycin-D 0.001μM R00 exp3  vs  THZ531 0.225μM R08 exp444">
{{:chemogenomics:comparison_plots:exp3_vs_exp444.png?nolink |}}
</modal>

<modal id="10" size="lg" title="Lead acetate 2000μM R08 exp497  vs  THZ531 0.225μM R08 exp444">
{{:chemogenomics:comparison_plots:exp444_vs_exp497.png?nolink |}}
</modal>

<modal id="11" size="lg" title="Pyridostatin 4μM R05 exp240  vs  THZ531 0.225μM R08 exp444">
{{:chemogenomics:comparison_plots:exp240_vs_exp444.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^
|negative regulation of protein neddylation|368.20|RPL11,RPL5|
|regulation of mRNA binding|220.92|EIF3E,EIF4G1|
|erythrocyte maturation|110.46|ZBTB7A,HEATR3,BRD1|
|Sin3 complex|78.90|SINHCAF,BRMS1,HDAC2|
|Sin3-type complex|78.90|SINHCAF,BRMS1,HDAC2|
|cytoplasmic translational initiation|76.18|EIF4A1,EIF3G,EIF3E,EIF4G1|
|negative regulation of stem cell population maintenance|69.04|SINHCAF,BRMS1,HDAC2|
|regulation of peptidyl-lysine acetylation|61.37|SOX4,TADA2A,HDAC2|
|translation initiation factor activity|46.02|EIF4A1,EIF3G,EIF3E,EIF4G1|
|translational initiation|34.52|EIF4A1,EIF3G,EIF3E,EIF4G1|
|cytoplasmic translation|29.85|EIF4A1,RPL11,RPL5,EIF3G,EIF3E,EIF4G1|
|translation factor activity, RNA binding|27.62|EIF4A1,EIF3G,EIF3E,EIF4G1|
|histone deacetylase complex|27.62|SINHCAF,RCOR1,BRMS1,HDAC2|
|negative regulation of transforming growth factor beta receptor signaling pathway|24.55|ZBTB7A,SINHCAF,BRMS1,HDAC2|
|erythrocyte differentiation|23.75|ZBTB7A,HEATR3,RCOR1,BRD1|
|erythrocyte homeostasis|21.66|ZBTB7A,HEATR3,RCOR1,BRD1|
|regulation of signal transduction by p53 class mediator|21.66|RPL11,RPL5,SOX4,HEXIM1|
|amide biosynthetic process|8.78|EIF4A1,RPL11,RPL5,ACSL4,DEGS1,EIF3G,EIF3E,EIF4G1|
|chromatin organization|6.27|BEND3,ZBTB7A,TADA2A,RCOR1,MBTD1,BRD1,UCHL5,HDAC2|
</modal>