====== Rucaparib 6.5μM R08 exp520 ======
==== Mechanism of Action ====
PARP1/2/3 inhibitor (Clovis), PARP1 mediates single-strand break repair, which can lead to replication-induced double strand breaks to form if not repaired; specifically target cancer with BRCA1, BRCA2 or PALB2 mutations; FDA granted an accelerated approval for use in cases of pretreated advanced ovarian cancer
  * **<color #00a2e8>Class / Subclass 1:</color>** DNA Damage, Repair and Replication / DNA Repair Inhibitor




==== Technical Notes ====
<accordion collapsed='true'>
<panel title='Compound References' collapsed='true'>
    * **<color #00a2e8>PubChem Name:</color>** %%Rucaparib phosphate%%
    * **<color #00a2e8>Synonyms:</color>** AG-014699 phosphate; PF-01367338 phosphate
    * **<color #00a2e8>CAS #:</color>** 459868-92-9
    * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/9931953|9931953]]
    * **<color #00a2e8>IUPAC:</color>** %%6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one;phosphoric acid%%
    * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C19H18FN3O.H3O4P/c1-21-10-11-2-4-12(5-3-11)18-14-6-7-22-19(24)15-8-13(20)9-16(23-18)17(14)15;1-5(2,3)4/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24);(H3,1,2,3,4)
    * **<color #00a2e8>INCHI Key:</color>** FCCGJTKEKXUBFZ-UHFFFAOYSA-N
    * **<color #00a2e8>Molecular Weight:</color>** 421.4
    * **<color #00a2e8>Canonical SMILES:</color>** CNCC1=CC=C(C=C1)C2=C3CCNC(=O)C4=C3C(=CC(=C4)F)N2.OP(=O)(O)O
    * **<color #00a2e8>Isomeric SMILES:</color>** N/A
    * **<color #00a2e8>Molecular Formula:</color>** C19H21FN3O5P
{{:chemogenomics:structures:chem-0325.svg?nolink}}
</panel>


<panel title='Compound Supplier' collapsed='true'>
    * **<color #00a2e8>Supplier Name:</color>** Med Chem Express
    * **<color #00a2e8>Catalog #:</color>** HY-10617
    * **<color #00a2e8>Lot #:</color>** 29562
</panel>


<panel title='Compound Characterization' collapsed='true'>
    * **<color #00a2e8>HRMS (ESI-TOF) m/z:</color>** (M+H)+ Calcd for C19H18FN3O 324.15067; found 324.15184
</panel>


<panel title='Dose Response Curve' collapsed='true'>
    * **<color #00a2e8>Platform ID:</color>** Rucaparib
    * **<color #00a2e8>Min:</color>** 4.0175; **<color #00a2e8>Max:</color>** 99.5587
{{:chemogenomics:dose_response:dr_578.png?nolink&500 |}}
\\ 
\\ 
\\ 
\\ 
|< 300px 100px 200px >|
^ IC   ^ Concentration (µM) ^
| IC10  |3.6040    |
| IC20  |5.1380    |
| IC30  |6.5040    |
| IC40  |7.8900    |
| IC50  |9.4220    |
| IC60  |11.2500    |
| IC70  |13.6500    |
| IC80  |17.2800    |
| IC90  |24.6300    |
\\ 
</panel>
</accordion>
==== Screen Summary ====
    * **<color #00a2e8>Round</color>**: 08
    * **<color #00a2e8>Dose</color>**: 6.5µM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 3.6
    * **<color #00a2e8>Numbers of reads</color>**: 16082760


==== 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^
|36/13|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Rucaparib_6.5uM_Round-8_exp520.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='Rucaparib 6.5μM R08 exp520'>
{{:chemogenomics:cranks_plots:exp520.png?nolink}}
</modal>


<modal id="modal_hits" size="sm" title="Top 30 S/R Genes">
^Gene^CRANKS Score^FDR^
|[[:human_genes:D:DNPH1|DNPH1]]|-4.79|0.00|
|[[:human_genes:S:SPIDR|SPIDR]]|-3.96|0.00|
|[[:human_genes:P:PRDX1|PRDX1]]|-3.74|0.00|
|[[:human_genes:S:SWSAP1|SWSAP1]]|-3.62|0.00|
|[[:human_genes:R:RAD54L|RAD54L]]|-3.57|0.00|
|[[:human_genes:M:MCM9|MCM9]]|-3.54|0.00|
|[[:human_genes:C:C19orf40|C19orf40]]|-3.40|<0.01|
|[[:human_genes:A:APITD1|APITD1]]|-3.39|0.00|
|[[:human_genes:R:RNF168|RNF168]]|-3.30|0.00|
|[[:human_genes:O:OTUB1|OTUB1]]|-3.27|0.00|
|[[:human_genes:A:APITD1-CORT|APITD1-CORT]]|-3.26|0.00|
|[[:human_genes:M:MUS81|MUS81]]|-3.23|<0.01|
|[[:human_genes:P:POLB|POLB]]|-3.21|0.00|
|[[:human_genes:Z:ZSWIM7|ZSWIM7]]|-3.17|0.00|
|[[:human_genes:C:C4orf27|C4orf27]]|-3.11|0.00|
|[[:human_genes:C:CHD1L|CHD1L]]|-3.07|0.00|
|[[:human_genes:V:VPS25|VPS25]]|-2.92|0.13|
|[[:human_genes:U:UBE2N|UBE2N]]|-2.79|<0.01|
|[[:human_genes:S:SWI5|SWI5]]|-2.75|<0.01|
|[[:human_genes:P:PNKP|PNKP]]|-2.74|0.10|
|[[:human_genes:H:H2AFX|H2AFX]]|-2.73|0.01|
|[[:human_genes:M:MCM8|MCM8]]|-2.72|0.01|
|[[:human_genes:Z:ZP3|ZP3]]|-2.70|<0.01|
|[[:human_genes:U:UBE2A|UBE2A]]|-2.69|<0.01|
|[[:human_genes:K:KPNA4|KPNA4]]|-2.65|<0.01|
|[[:human_genes:E:ESCO2|ESCO2]]|-2.62|<0.01|
|[[:human_genes:I:ITPA|ITPA]]|-2.62|<0.01|
|[[:human_genes:S:SIVA1|SIVA1]]|-2.62|<0.01|
|[[:human_genes:C:CSK|CSK]]|-2.48|0.01|
|[[:human_genes:P:PSMA5|PSMA5]]|-2.47|0.12|
|[[:human_genes:E:EBF1|EBF1]]|2.10|0.30|
|[[:human_genes:O:ODC1|ODC1]]|2.11|0.15|
|[[:human_genes:S:SRM|SRM]]|2.12|0.15|
|[[:human_genes:P:PIK3R1|PIK3R1]]|2.14|0.14|
|[[:human_genes:A:ASUN|ASUN]]|2.21|0.11|
|[[:human_genes:N:NUP155|NUP155]]|2.22|0.15|
|[[:human_genes:D:DDX39B|DDX39B]]|2.23|0.15|
|[[:human_genes:S:SLC25A32|SLC25A32]]|2.26|0.15|
|[[:human_genes:P:PCIF1|PCIF1]]|2.35|0.06|
|[[:human_genes:R:RCAN3|RCAN3]]|2.37|0.10|
|[[:human_genes:I:ITPKB|ITPKB]]|2.39|0.09|
|[[:human_genes:G:GTF3A|GTF3A]]|2.41|0.24|
|[[:human_genes:A:AKT2|AKT2]]|2.42|0.09|
|[[:human_genes:C:CD19|CD19]]|2.42|0.09|
|[[:human_genes:D:DPH1|DPH1]]|2.43|0.04|
|[[:human_genes:A:APAF1|APAF1]]|2.45|0.04|
|[[:human_genes:S:SHMT2|SHMT2]]|2.49|0.11|
|[[:human_genes:R:RHOH|RHOH]]|2.55|0.05|
|[[:human_genes:H:HSPA5|HSPA5]]|2.64|0.33|
|[[:human_genes:P:PHC1|PHC1]]|2.65|0.02|
|[[:human_genes:S:SLFN11|SLFN11]]|2.65|0.02|
|[[:human_genes:E:EIF4G1|EIF4G1]]|2.69|0.03|
|[[:human_genes:Z:ZNF330|ZNF330]]|2.71|0.03|
|[[:human_genes:P:PARP2|PARP2]]|2.74|0.03|
|[[:human_genes:M:MLST8|MLST8]]|2.91|<0.01|
|[[:human_genes:M:MAPKAP1|MAPKAP1]]|2.98|<0.01|
|[[:human_genes:R:RICTOR|RICTOR]]|3.39|<0.01|
|[[:human_genes:A:ADPRHL2|ADPRHL2]]|3.57|<0.01|
|[[:human_genes:T:TP53|TP53]]|4.88|<0.01|
|[[:human_genes:P:PARP1|PARP1]]|7.51|<0.01|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp526|Sulforaphane 9μM R08 exp526 no dilution day6]]|0.088|<button type="primary" size="small" modal="1">View</button>|
|[[:results:exp525|Sulforaphane 9μM R08 exp525]]|0.088|<button type="primary" size="small" modal="2">View</button>|
|[[:results:exp299|Talazoparib 0.006μM R06 exp299]]|0.077|<button type="primary" size="small" modal="3">View</button>|
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|0.057|<button type="primary" size="small" modal="4">View</button>|
|[[:results:exp512|Olaparib 4μM R08 exp512]]|0.204|<button type="primary" size="small" modal="5">View</button>|
|[[:results:exp270|Campthothecin 0.001μM R06 exp270]]|0.081|<button type="primary" size="small" modal="6">View</button>|
|[[:results:exp354|Diepoxybutane 3μM R07 exp354]]|0.076|<button type="primary" size="small" modal="7">View</button>|
|[[:results:exp116|AICAR 240μM R03 exp116]]|0.073|<button type="primary" size="small" modal="8">View</button>|
|[[:results:exp294|Nutlin-3A 1.6μM R06 exp294]]|0.071|<button type="primary" size="small" modal="9">View</button>|
|[[:results:exp440|Aphidicolin 0.4μM R08 exp440]]|0.069|<button type="primary" size="small" modal="10">View</button>|
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|0.065|<button type="primary" size="small" modal="11">View</button>|
|[[:results:exp134|MS023 2μM R03 exp134]]|0.055|<button type="primary" size="small" modal="12">View</button>|
|[[:results:exp517|Quercetin 20μM R08 exp517]]|0.055|<button type="primary" size="small" modal="13">View</button>|
|[[:results:exp78|Pterostilbene 16μM R02 exp78]]|0.054|<button type="primary" size="small" modal="14">View</button>|
|[[:results:exp360|Genistein 15μM R07 exp360]]|0.053|<button type="primary" size="small" modal="15">View</button>|
|[[:results:exp147|Resveratrol 16μM R03 exp147]]|0.052|<button type="primary" size="small" modal="16">View</button>|
|[[:results:exp505|ML-792 0.2μM R08 exp505]]|0.052|<button type="primary" size="small" modal="17">View</button>|
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|0.051|<button type="primary" size="small" modal="18">View</button>|
|[[:results:exp498|Lead acetate 2000μM R08 exp498 no dilution day6]]|0.051|<button type="primary" size="small" modal="19">View</button>|
|[[:results:exp453|B02 10μM R08 exp453]]|0.051|<button type="primary" size="small" modal="20">View</button>|
</modal>


<modal id="1" size="lg" title="Rucaparib 6.5μM R08 exp520  vs  Sulforaphane 9μM R08 exp526 no dilution day6">
{{:chemogenomics:comparison_plots:exp520_vs_exp526.png?nolink |}}
</modal>

<modal id="2" size="lg" title="Rucaparib 6.5μM R08 exp520  vs  Sulforaphane 9μM R08 exp525">
{{:chemogenomics:comparison_plots:exp520_vs_exp525.png?nolink |}}
</modal>

<modal id="3" 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="4" size="lg" title="Rucaparib 6.5μM R08 exp520  vs  Trimetrexate 0.03μM R08 exp535">
{{:chemogenomics:comparison_plots:exp520_vs_exp535.png?nolink |}}
</modal>

<modal id="5" size="lg" title="Olaparib 4μM R08 exp512  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp512_vs_exp520.png?nolink |}}
</modal>

<modal id="6" size="lg" title="Campthothecin 0.001μM R06 exp270  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp270_vs_exp520.png?nolink |}}
</modal>

<modal id="7" size="lg" title="Diepoxybutane 3μM R07 exp354  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp354_vs_exp520.png?nolink |}}
</modal>

<modal id="8" size="lg" title="AICAR 240μM R03 exp116  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp116_vs_exp520.png?nolink |}}
</modal>

<modal id="9" size="lg" title="Nutlin-3A 1.6μM R06 exp294  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp294_vs_exp520.png?nolink |}}
</modal>

<modal id="10" size="lg" title="Aphidicolin 0.4μM R08 exp440  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp440_vs_exp520.png?nolink |}}
</modal>

<modal id="11" size="lg" title="Etoposide 0.1μM R05 exp198  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp198_vs_exp520.png?nolink |}}
</modal>

<modal id="12" size="lg" title="MS023 2μM R03 exp134  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp134_vs_exp520.png?nolink |}}
</modal>

<modal id="13" size="lg" title="Quercetin 20μM R08 exp517  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp517_vs_exp520.png?nolink |}}
</modal>

<modal id="14" size="lg" title="Pterostilbene 16μM R02 exp78  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp520_vs_exp78.png?nolink |}}
</modal>

<modal id="15" size="lg" title="Genistein 15μM R07 exp360  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp360_vs_exp520.png?nolink |}}
</modal>

<modal id="16" size="lg" title="Resveratrol 16μM R03 exp147  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp147_vs_exp520.png?nolink |}}
</modal>

<modal id="17" size="lg" title="ML-792 0.2μM R08 exp505  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp505_vs_exp520.png?nolink |}}
</modal>

<modal id="18" size="lg" title="Lead acetate 2000μM R08 exp497  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp497_vs_exp520.png?nolink |}}
</modal>

<modal id="19" size="lg" title="Lead acetate 2000μM R08 exp498 no dilution day6  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp498_vs_exp520.png?nolink |}}
</modal>

<modal id="20" size="lg" title="B02 10μM R08 exp453  vs  Rucaparib 6.5μM R08 exp520">
{{:chemogenomics:comparison_plots:exp453_vs_exp520.png?nolink |}}
</modal>



<modal id="modal_go_sensitive" size="lg" title="Top 30 sensitive GO terms">
^GO Term^Fold Change^Genes^
|MutSbeta complex binding|637.27|MCM9,MCM8|
|interstrand cross-link repair|74.97|MCM9,CENPS,RNF168,MCM8|
|recombinational repair|53.55|SPIDR,SWSAP1,RAD54L,MCM9,MUS81,ZSWIM7,UBE2N,SWI5,H2AX,MCM8|
|double-strand break repair via homologous recombination|49.44|SPIDR,RAD54L,MCM9,MUS81,ZSWIM7,UBE2N,SWI5,H2AX,MCM8|
|DNA-templated DNA replication maintenance of fidelity|48.10|MCM9,CENPS,MUS81,MCM8|
|double-strand break repair|44.39|SPIDR,SWSAP1,RAD54L,MCM9,RNF168,MUS81,POLB,ZSWIM7,UBE2N,SWI5,PNKP,H2AX,MCM8,ESCO2|
|site of double-strand break|39.34|RNF168,CHD1L,PNKP,H2AX,ESCO2|
|DNA recombination|37.15|SPIDR,SWSAP1,RAD54L,MCM9,CENPS,RNF168,MUS81,POLB,ZSWIM7,UBE2N,SWI5,H2AX,MCM8|
|site of DNA damage|29.50|RNF168,CHD1L,PNKP,H2AX,ESCO2|
|DNA-templated DNA replication|29.41|MCM9,CENPS,MUS81,POLB,PNKP,MCM8|
|response to ionizing radiation|28.97|SPIDR,RAD54L,RNF168,POLB,SWI5,H2AX|
|positive regulation of DNA repair|26.33|SPIDR,RNF168,UBE2N,PNKP,H2AX|
|DNA repair|24.46|SPIDR,SWSAP1,RAD54L,MCM9,CENPS,RNF168,OTUB1,MUS81,POLB,ZSWIM7,CHD1L,UBE2N,SWI5,PNKP,H2AX,MCM8,UBE2A,ESCO2|
|DNA replication|19.81|MCM9,CENPS,MUS81,POLB,PNKP,MCM8|
|regulation of DNA repair|19.02|SPIDR,RNF168,OTUB1,UBE2N,PNKP,H2AX|
|catalytic activity, acting on DNA|16.27|RAD54L,MCM9,MUS81,POLB,CHD1L,MCM8|
|DNA damage response|16.11|SPIDR,SWSAP1,RAD54L,MCM9,CENPS,RNF168,OTUB1,MUS81,POLB,ZSWIM7,CHD1L,UBE2N,SWI5,PNKP,H2AX,MCM8,UBE2A,ESCO2|
|DNA metabolic process|16.07|SPIDR,SWSAP1,RAD54L,MCM9,CENPS,RNF168,OTUB1,MUS81,POLB,ZSWIM7,CHD1L,UBE2N,SWI5,PNKP,H2AX,MCM8,UBE2A,ESCO2|
|response to radiation|12.46|SPIDR,RAD54L,RNF168,POLB,SWI5,PNKP,H2AX,UBE2A|
</modal>
<modal id="modal_go_resistant" size="lg" title="Top 30 resistant GO terms">
^GO Term^Fold Change^Genes^
|NAD DNA ADP-ribosyltransferase activity|552.30|PARP1,PARP2|
|NAD+-protein-glutamate ADP-ribosyltransferase activity|368.20|PARP1,PARP2|
|NAD+- protein-aspartate ADP-ribosyltransferase activity|276.15|PARP1,PARP2|
|TORC2 complex|207.11|RICTOR,MAPKAP1,MLST8|
|TOR signaling|47.34|RICTOR,MAPKAP1,MLST8|
|site of DNA damage|25.57|PARP1,TP53,ADPRS,PARP2,SLFN11|
|neuron apoptotic process|21.87|TP53,PARP2,APAF1,AKT2|
|cellular response to light stimulus|20.27|PARP1,TP53,AKT2,PIK3R1|
|positive regulation of cell growth|17.82|RICTOR,MAPKAP1,MLST8,PARP2,EIF4G1|
|cellular response to nutrient levels|14.22|TP53,RICTOR,MAPKAP1,MLST8,EIF4G1,HSPA5|
|cellular response to extracellular stimulus|12.65|TP53,RICTOR,MAPKAP1,MLST8,EIF4G1,HSPA5|
|cellular response to external stimulus|10.13|TP53,RICTOR,MAPKAP1,MLST8,EIF4G1,HSPA5|
|response to nutrient levels|9.34|TP53,RICTOR,MAPKAP1,MLST8,PARP2,EIF4G1,HSPA5,APAF1|
|response to extracellular stimulus|8.80|TP53,RICTOR,MAPKAP1,MLST8,PARP2,EIF4G1,HSPA5,APAF1|
|positive regulation of phosphorylation|6.91|TP53,RICTOR,MAPKAP1,MLST8,EIF4G1,CD19,AKT2,PDPK1|
|positive regulation of phosphate metabolic process|6.28|TP53,RICTOR,MAPKAP1,MLST8,EIF4G1,CD19,AKT2,PDPK1|
|positive regulation of phosphorus metabolic process|6.27|TP53,RICTOR,MAPKAP1,MLST8,EIF4G1,CD19,AKT2,PDPK1|
|negative regulation of programmed cell death|6.18|TP53,ADPRS,RICTOR,MAPKAP1,MLST8,HSPA5,AKT2,ITPKB,PIK3R1,PDPK1|
|negative regulation of apoptotic process|5.73|TP53,RICTOR,MAPKAP1,MLST8,HSPA5,AKT2,ITPKB,PIK3R1,PDPK1|
</modal>