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Ask your administrator if you think this is wrong. ====== 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 |}} \\ \\ \\ \\ |< 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> Last modified: 2026/01/15 21:36by 127.0.0.1