====== Talazoparib 0.006μM R06 exp299 ======
==== Mechanism of Action ====
Inhibits PARP1 and PARP2, blocks ssDNA break repair, selectively toxic to BRCA1/2 negative cancers
  * **<color #00a2e8>Class / Subclass 1:</color>** DNA Damage, Repair and Replication / PARP Inhibitor




==== Technical Notes ====
<accordion collapsed='true'>
<panel title='Compound References' collapsed='true'>
    * **<color #00a2e8>PubChem Name:</color>** %%Talazoparib%%
    * **<color #00a2e8>Synonyms:</color>** BMN-673; LT-673
    * **<color #00a2e8>CAS #:</color>** 1207456-01-6
    * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/135565082|135565082]]
    * **<color #00a2e8>IUPAC:</color>** %%(11S,12R)-7-fluoro-11-(4-fluorophenyl)-12-(2-methyl-1,2,4-triazol-3-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one%%
    * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C19H14F2N6O/c1-27-18(22-8-23-27)15-16(9-2-4-10(20)5-3-9)24-13-7-11(21)6-12-14(13)17(15)25-26-19(12)28/h2-8,15-16,24H,1H3,(H,26,28)/t15-,16-/m1/s1
    * **<color #00a2e8>INCHI Key:</color>** HWGQMRYQVZSGDQ-HZPDHXFCSA-N
    * **<color #00a2e8>Molecular Weight:</color>** 380.4
    * **<color #00a2e8>Canonical SMILES:</color>** CN1C(=NC=N1)C2C(NC3=CC(=CC4=C3C2=NNC4=O)F)C5=CC=C(C=C5)F
    * **<color #00a2e8>Isomeric SMILES:</color>** CN1C(=NC=N1)[C@@H]2[C@H](NC3=CC(=CC4=C3C2=NNC4=O)F)C5=CC=C(C=C5)F
    * **<color #00a2e8>Molecular Formula:</color>** C19H14F2N6O
{{:chemogenomics:structures:chem-0186.svg?nolink}}
</panel>


<panel title='Compound Supplier' collapsed='true'>
    * **<color #00a2e8>Supplier Name:</color>** Med Chem Express
    * **<color #00a2e8>Catalog #:</color>** HY-16106
    * **<color #00a2e8>Lot #:</color>** 8329
</panel>


<panel title='Compound Characterization' collapsed='true'>
Characterization data not available.
</panel>


<panel title='Dose Response Curve' collapsed='true'>
    * **<color #00a2e8>Platform ID:</color>** Talazoparib
    * **<color #00a2e8>Min:</color>** 3.9365; **<color #00a2e8>Max:</color>** 86.6319
{{:chemogenomics:dose_response:dr_320.png?nolink&500 |}}
\\ 
\\ 
\\ 
\\ 
|< 300px 100px 200px >|
^ IC   ^ Concentration (µM) ^
| IC10  |N/A    |
| IC20  |N/A    |
| IC30  |0.0035    |
| IC40  |N/A    |
| IC50  |0.0099    |
| 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>**: 6nM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 6.7
    * **<color #00a2e8>Numbers of reads</color>**: 17426951


==== 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^
|5/16|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Talazoparib_0.006uM_Round-6_exp299.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='Talazoparib 0.006μM R06 exp299'>
{{:chemogenomics:cranks_plots:exp299.png?nolink}}
</modal>


<modal id="modal_hits" size="sm" title="Top 30 S/R Genes">
^Gene^CRANKS Score^FDR^
|[[:human_genes:M:MCM9|MCM9]]|-4.81|<0.01|
|[[:human_genes:S:SOD1|SOD1]]|-3.01|0.08|
|[[:human_genes:H:H2AFX|H2AFX]]|-3.00|0.02|
|[[:human_genes:P:PRAMEF25|PRAMEF25]]|-3.00|0.31|
|[[:human_genes:P:PRAMEF26|PRAMEF26]]|-2.94|0.34|
|[[:human_genes:Z:ZSCAN12|ZSCAN12]]|-2.92|0.10|
|[[:human_genes:M:MSI2|MSI2]]|-2.77|0.03|
|[[:human_genes:A:ATP6V0B|ATP6V0B]]|-2.70|0.16|
|[[:human_genes:P:PTEN|PTEN]]|-2.67|0.03|
|[[:human_genes:X:XRCC1|XRCC1]]|-2.64|0.03|
|[[:human_genes:R:RFC3|RFC3]]|-2.62|0.32|
|[[:human_genes:S:SPIDR|SPIDR]]|-2.54|0.05|
|[[:human_genes:C:CD28|CD28]]|-2.49|0.05|
|[[:human_genes:C:CNOT8|CNOT8]]|-2.47|0.05|
|[[:human_genes:R:RIF1|RIF1]]|-2.46|0.05|
|[[:human_genes:D:DNPH1|DNPH1]]|-2.42|0.06|
|[[:human_genes:S:SNF8|SNF8]]|-2.42|0.08|
|[[:human_genes:R:RNF168|RNF168]]|-2.39|0.07|
|[[:human_genes:T:TCF4|TCF4]]|-2.37|0.07|
|[[:human_genes:H:HELQ|HELQ]]|-2.35|0.07|
|[[:human_genes:S:SMARCAL1|SMARCAL1]]|-2.30|0.08|
|[[:human_genes:S:SWSAP1|SWSAP1]]|-2.29|0.08|
|[[:human_genes:M:MSL3|MSL3]]|-2.28|0.12|
|[[:human_genes:S:SFR1|SFR1]]|-2.28|0.08|
|[[:human_genes:E:EXTL1|EXTL1]]|-2.27|0.18|
|[[:human_genes:C:C16orf72|C16orf72]]|-2.27|0.12|
|[[:human_genes:B:BAG2|BAG2]]|-2.26|0.08|
|[[:human_genes:T:TSC2|TSC2]]|-2.25|0.08|
|[[:human_genes:D:DEPDC5|DEPDC5]]|-2.25|0.08|
|[[:human_genes:R:RNASEH2A|RNASEH2A]]|-2.20|0.22|
|[[:human_genes:A:AK2|AK2]]|2.18|0.11|
|[[:human_genes:S:SUMO2|SUMO2]]|2.20|0.26|
|[[:human_genes:M:MBTPS1|MBTPS1]]|2.22|0.25|
|[[:human_genes:I:IMP4|IMP4]]|2.22|0.58|
|[[:human_genes:P:PIK3CD|PIK3CD]]|2.24|0.08|
|[[:human_genes:P:PAF1|PAF1]]|2.28|0.12|
|[[:human_genes:T:THOC2|THOC2]]|2.30|0.41|
|[[:human_genes:E:EIF4A1|EIF4A1]]|2.30|0.20|
|[[:human_genes:P:PCBP2|PCBP2]]|2.31|0.06|
|[[:human_genes:Z:ZBTB22|ZBTB22]]|2.37|0.05|
|[[:human_genes:R:RPS11|RPS11]]|2.44|0.30|
|[[:human_genes:M:MDH1|MDH1]]|2.46|0.03|
|[[:human_genes:P:PFKP|PFKP]]|2.56|0.02|
|[[:human_genes:M:ME2|ME2]]|2.57|0.02|
|[[:human_genes:P:PGP|PGP]]|2.61|0.06|
|[[:human_genes:K:KHDRBS1|KHDRBS1]]|2.63|0.03|
|[[:human_genes:U:UBE2I|UBE2I]]|2.81|0.06|
|[[:human_genes:S:SAE1|SAE1]]|2.83|0.03|
|[[:human_genes:H:HEATR3|HEATR3]]|2.89|<0.01|
|[[:human_genes:S:SLTM|SLTM]]|2.90|<0.01|
|[[:human_genes:U:U2AF2|U2AF2]]|3.11|0.06|
|[[:human_genes:T:TP53|TP53]]|3.51|<0.01|
|[[:human_genes:S:SENP1|SENP1]]|3.79|<0.01|
|[[:human_genes:I:IRF2|IRF2]]|4.51|<0.01|
|[[:human_genes:U:UBA2|UBA2]]|4.83|<0.01|
|[[:human_genes:T:TOP3A|TOP3A]]|6.23|<0.01|
|[[:human_genes:B:BLM|BLM]]|7.65|<0.01|
|[[:human_genes:P:PML|PML]]|8.22|<0.01|
|[[:human_genes:R:RMI1|RMI1]]|8.25|<0.01|
|[[:human_genes:R:RMI2|RMI2]]|8.50|<0.01|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|0.057|<button type="primary" size="small" modal="1">View</button>|
|[[:results:exp512|Olaparib 4μM R08 exp512]]|0.088|<button type="primary" size="small" modal="2">View</button>|
|[[:results:exp354|Diepoxybutane 3μM R07 exp354]]|0.078|<button type="primary" size="small" modal="3">View</button>|
|[[:results:exp520|Rucaparib 6.5μM R08 exp520]]|0.077|<button type="primary" size="small" modal="4">View</button>|
|[[:results:exp360|Genistein 15μM R07 exp360]]|0.074|<button type="primary" size="small" modal="5">View</button>|
|[[:results:exp294|Nutlin-3A 1.6μM R06 exp294]]|0.067|<button type="primary" size="small" modal="6">View</button>|
|[[:results:exp78|Pterostilbene 16μM R02 exp78]]|0.059|<button type="primary" size="small" modal="7">View</button>|
|[[:results:exp216|Erlotinib 10μM R05 exp216]]|0.053|<button type="primary" size="small" modal="8">View</button>|
|[[:results:exp184|Ixabepilone 0.004 to 0.005μM on day4 R04 exp184]]|0.052|<button type="primary" size="small" modal="9">View</button>|
|[[:results:exp270|Campthothecin 0.001μM R06 exp270]]|0.052|<button type="primary" size="small" modal="10">View</button>|
</modal>


<modal id="1" size="lg" title="Talazoparib 0.006μM R06 exp299  vs  Trimetrexate 0.03μM R08 exp535">
{{:chemogenomics:comparison_plots:exp299_vs_exp535.png?nolink |}}
</modal>

<modal id="2" size="lg" title="Olaparib 4μM R08 exp512  vs  Talazoparib 0.006μM R06 exp299">
{{:chemogenomics:comparison_plots:exp299_vs_exp512.png?nolink |}}
</modal>

<modal id="3" size="lg" title="Diepoxybutane 3μM R07 exp354  vs  Talazoparib 0.006μM R06 exp299">
{{:chemogenomics:comparison_plots:exp299_vs_exp354.png?nolink |}}
</modal>

<modal id="4" size="lg" title="Rucaparib 6.5μM R08 exp520  vs  Talazoparib 0.006μM R06 exp299">
{{:chemogenomics:comparison_plots:exp299_vs_exp520.png?nolink |}}
</modal>

<modal id="5" size="lg" title="Genistein 15μM R07 exp360  vs  Talazoparib 0.006μM R06 exp299">
{{:chemogenomics:comparison_plots:exp299_vs_exp360.png?nolink |}}
</modal>

<modal id="6" 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="7" size="lg" title="Pterostilbene 16μM R02 exp78  vs  Talazoparib 0.006μM R06 exp299">
{{:chemogenomics:comparison_plots:exp299_vs_exp78.png?nolink |}}
</modal>

<modal id="8" size="lg" title="Erlotinib 10μM R05 exp216  vs  Talazoparib 0.006μM R06 exp299">
{{:chemogenomics:comparison_plots:exp216_vs_exp299.png?nolink |}}
</modal>

<modal id="9" size="lg" title="Ixabepilone 0.004 to 0.005μM on day4 R04 exp184  vs  Talazoparib 0.006μM R06 exp299">
{{:chemogenomics:comparison_plots:exp184_vs_exp299.png?nolink |}}
</modal>

<modal id="10" size="lg" title="Campthothecin 0.001μM R06 exp270  vs  Talazoparib 0.006μM R06 exp299">
{{:chemogenomics:comparison_plots:exp270_vs_exp299.png?nolink |}}
</modal>



<modal id="modal_go_sensitive" size="lg" title="Top 30 sensitive GO terms">
^GO Term^Fold Change^Genes^
|single-stranded DNA helicase activity|86.92|MCM9,RFC3,HELQ|
|double-strand break repair via nonhomologous end joining|60.70|XRCC1,RNF168,HELQ,SMARCAL1|
|recombinational repair|37.49|MCM9,H2AX,XRCC1,SPIDR,HELQ,SWSAP1,SFR1|
|site of DNA damage|35.41|H2AX,XRCC1,RIF1,RNF168,HELQ,SMARCAL1|
|double-strand break repair via homologous recombination|32.97|MCM9,H2AX,XRCC1,SPIDR,HELQ,SFR1|
|site of double-strand break|31.48|H2AX,RIF1,RNF168,SMARCAL1|
|positive regulation of DNA repair|31.35|H2AX,XRCC1,SPIDR,RIF1,RNF168,HELQ|
|double-strand break repair|28.54|MCM9,H2AX,XRCC1,SPIDR,RNF168,HELQ,SMARCAL1,SWSAP1,SFR1|
|DNA recombination|22.66|MCM9,H2AX,XRCC1,SPIDR,RNF168,HELQ,SWSAP1,SFR1|
|ATP-dependent activity, acting on DNA|22.17|MCM9,RFC3,HELQ,SMARCAL1|
|regulation of DNA recombination|20.08|SPIDR,CD28,RIF1,HELQ|
|regulation of DNA repair|18.93|H2AX,XRCC1,SPIDR,RIF1,RNF168,HELQ|
|positive regulation of DNA metabolic process|17.77|H2AX,XRCC1,RFC3,SPIDR,CD28,RIF1,RNF168,HELQ|
|DNA repair|14.89|MCM9,H2AX,XRCC1,RFC3,SPIDR,RIF1,RNF168,HELQ,SMARCAL1,SWSAP1,SFR1|
|catalytic activity, acting on DNA|13.45|MCM9,XRCC1,RFC3,HELQ,SMARCAL1|
|regulation of DNA metabolic process|10.06|H2AX,XRCC1,RFC3,SPIDR,CD28,RIF1,RNF168,HELQ|
|DNA damage response|9.81|MCM9,H2AX,XRCC1,RFC3,SPIDR,RIF1,RNF168,HELQ,SMARCAL1,SWSAP1,SFR1|
|DNA metabolic process|9.79|MCM9,H2AX,XRCC1,RFC3,SPIDR,RIF1,RNF168,HELQ,SMARCAL1,SWSAP1,SFR1|
|chromosome organization|8.65|MCM9,XRCC1,RFC3,RIF1,HELQ,SMARCAL1|
</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|552.40|RMI2,RMI1,BLM|
|resolution of recombination intermediates|331.44|RMI2,RMI1,BLM|
|small protein activating enzyme binding|276.20|UBA2,SAE1|
|regulation of protein sumoylation|75.33|UBA2,SAE1,UBE2I|
|protein sumoylation|64.99|PML,UBA2,SENP1,SAE1,UBE2I,SUMO2|
|PML body|31.57|PML,BLM,TOP3A,TP53,UBE2I,SUMO2|
|mitotic DNA damage checkpoint signaling|27.97|PML,BLM,TP53,MBTPS1|
|mitotic DNA integrity checkpoint signaling|26.62|PML,BLM,TP53,MBTPS1|
|peptidyl-lysine modification|20.21|PML,UBA2,SENP1,SAE1,UBE2I,SUMO2|
|double-strand break repair|13.74|RMI2,RMI1,BLM,TOP3A,TP53|
|nuclear body|7.50|RMI2,RMI1,PML,BLM,TOP3A,TP53,U2AF2,SLTM,UBE2I,THOC2,SUMO2|
</modal>