BI-2536 0.0042μM R03 exp95 [The Human Chemical-Genetic Interaction Map Project]

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====== BI-2536 0.0042μM R03 exp95 ======
==== Mechanism of Action ====
Inhibits PLK1 kinase, causes G2/M arrest
  * **<color #00a2e8>Class / Subclass 1:</color>** Cell Cycle / Mitotic 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>** %%BI-2536%%
    * **<color #00a2e8>Synonyms:</color>** N/A
    * **<color #00a2e8>CAS #:</color>** 755038-02-9
    * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/11364421|11364421]]
    * **<color #00a2e8>IUPAC:</color>** %%4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide%%
    * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C28H39N7O3/c1-5-22-27(37)34(3)23-17-29-28(32-25(23)35(22)20-8-6-7-9-20)31-21-11-10-18(16-24(21)38-4)26(36)30-19-12-14-33(2)15-13-19/h10-11,16-17,19-20,22H,5-9,12-15H2,1-4H3,(H,30,36)(H,29,31,32)/t22-/m1/s1
    * **<color #00a2e8>INCHI Key:</color>** XQVVPGYIWAGRNI-JOCHJYFZSA-N
    * **<color #00a2e8>Molecular Weight:</color>** 521.7
    * **<color #00a2e8>Canonical SMILES:</color>** CCC1C(=O)N(C2=CN=C(N=C2N1C3CCCC3)NC4=C(C=C(C=C4)C(=O)NC5CCN(CC5)C)OC)C
    * **<color #00a2e8>Isomeric SMILES:</color>** CC[C@@H]1C(=O)N(C2=CN=C(N=C2N1C3CCCC3)NC4=C(C=C(C=C4)C(=O)NC5CCN(CC5)C)OC)C
    * **<color #00a2e8>Molecular Formula:</color>** C28H39N7O3
{{:chemogenomics:structures:chem-0022.svg?nolink}}
</panel>


<panel title='Compound Supplier' collapsed='true'>
    * **<color #00a2e8>Supplier Name:</color>** Med Chem Express
    * **<color #00a2e8>Catalog #:</color>** HY-50698
    * **<color #00a2e8>Lot #:</color>** N/A
</panel>


<panel title='Compound Characterization' collapsed='true'>
    * **<color #00a2e8>HRMS (ESI-TOF) m/z:</color>** (M+H)+ Calcd for C28H39N7O3 522.31871; found 522.32029
</panel>


<panel title='Dose Response Curve' collapsed='true'>
    * **<color #00a2e8>Platform ID:</color>** BI2536
    * **<color #00a2e8>Min:</color>** -5.0598; **<color #00a2e8>Max:</color>** 98.9203
{{:chemogenomics:dose_response:dr_74.png?nolink&500 |}}
\\ 
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|< 300px 100px 200px >|
^ IC   ^ Concentration (µM) ^
| IC10  |N/A    |
| IC20  |0.0014    |
| IC30  |0.0041    |
| IC40  |0.0097    |
| IC50  |0.0214    |
| IC60  |N/A    |
| IC70  |N/A    |
| IC80  |N/A    |
| IC90  |N/A    |
\\ 
</panel>
</accordion>
==== Screen Summary ====
    * **<color #00a2e8>Round</color>**: 03
    * **<color #00a2e8>Dose</color>**: 4.2nM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 4.4
    * **<color #00a2e8>Numbers of reads</color>**: 12660576


==== 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^
|36/37|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/BI-2536_0.0042uM_Round-3_exp95.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='BI-2536 0.0042μM R03 exp95'>
{{:chemogenomics:cranks_plots:exp95.png?nolink}}
</modal>


<modal id="modal_hits" size="sm" title="Top 30 S/R Genes">
^Gene^CRANKS Score^FDR^
|[[:human_genes:K:KIF18A|KIF18A]]|-4.36|<0.01|
|[[:human_genes:S:STMN1|STMN1]]|-4.07|<0.01|
|[[:human_genes:S:SKA1|SKA1]]|-4.01|<0.01|
|[[:human_genes:C:CENPB|CENPB]]|-3.41|<0.01|
|[[:human_genes:A:ACTR1A|ACTR1A]]|-3.36|<0.01|
|[[:human_genes:P:PDS5B|PDS5B]]|-3.26|<0.01|
|[[:human_genes:P:PRR14L|PRR14L]]|-3.17|<0.01|
|[[:human_genes:I:IVNS1ABP|IVNS1ABP]]|-3.13|<0.01|
|[[:human_genes:M:MLF1IP|MLF1IP]]|-2.92|<0.01|
|[[:human_genes:K:KIF15|KIF15]]|-2.90|<0.01|
|[[:human_genes:D:DCTN2|DCTN2]]|-2.81|0.01|
|[[:human_genes:V:VBP1|VBP1]]|-2.78|<0.01|
|[[:human_genes:E:EIF4E2|EIF4E2]]|-2.70|0.03|
|[[:human_genes:A:ACTR1B|ACTR1B]]|-2.69|0.01|
|[[:human_genes:G:GIGYF2|GIGYF2]]|-2.66|0.03|
|[[:human_genes:C:CENPL|CENPL]]|-2.66|0.02|
|[[:human_genes:P:PPP2R5C|PPP2R5C]]|-2.62|0.01|
|[[:human_genes:R:RBMX2|RBMX2]]|-2.59|0.02|
|[[:human_genes:C:CENPO|CENPO]]|-2.59|0.02|
|[[:human_genes:G:GAK|GAK]]|-2.54|0.02|
|[[:human_genes:K:KIAA1432|KIAA1432]]|-2.53|0.02|
|[[:human_genes:D:DPH2|DPH2]]|-2.51|0.02|
|[[:human_genes:L:LCMT1|LCMT1]]|-2.50|0.02|
|[[:human_genes:C:CENPN|CENPN]]|-2.50|0.02|
|[[:human_genes:D:DPH1|DPH1]]|-2.49|0.02|
|[[:human_genes:N:N6AMT1|N6AMT1]]|-2.48|0.11|
|[[:human_genes:C:CENPQ|CENPQ]]|-2.45|0.02|
|[[:human_genes:E:EEFSEC|EEFSEC]]|-2.41|0.05|
|[[:human_genes:C:CCNB1|CCNB1]]|-2.39|0.03|
|[[:human_genes:S:SNAPC5|SNAPC5]]|-2.38|0.05|
|[[:human_genes:I:IPMK|IPMK]]|2.40|0.05|
|[[:human_genes:Z:ZNF622|ZNF622]]|2.41|0.12|
|[[:human_genes:G:GP2|GP2]]|2.43|0.02|
|[[:human_genes:N:NUDT5|NUDT5]]|2.48|0.03|
|[[:human_genes:R:RIC8A|RIC8A]]|2.51|0.02|
|[[:human_genes:R:RPL27|RPL27]]|2.64|0.02|
|[[:human_genes:H:HEXIM1|HEXIM1]]|2.65|<0.01|
|[[:human_genes:I:IMPDH2|IMPDH2]]|2.66|0.02|
|[[:human_genes:E:EIF3A|EIF3A]]|2.67|<0.01|
|[[:human_genes:P:PATL1|PATL1]]|2.70|<0.01|
|[[:human_genes:F:FIP1L1|FIP1L1]]|2.71|0.03|
|[[:human_genes:R:RBM5|RBM5]]|2.72|<0.01|
|[[:human_genes:C:C1orf27|C1orf27]]|2.75|<0.01|
|[[:human_genes:U:UFL1|UFL1]]|2.76|<0.01|
|[[:human_genes:R:RPS27A|RPS27A]]|2.76|<0.01|
|[[:human_genes:P:PPRC1|PPRC1]]|2.77|<0.01|
|[[:human_genes:E:EIF3G|EIF3G]]|2.84|<0.01|
|[[:human_genes:E:EIF3J|EIF3J]]|2.92|0.06|
|[[:human_genes:K:KCMF1|KCMF1]]|3.00|<0.01|
|[[:human_genes:Y:YWHAE|YWHAE]]|3.02|<0.01|
|[[:human_genes:M:MBTPS2|MBTPS2]]|3.04|<0.01|
|[[:human_genes:U:UFSP2|UFSP2]]|3.10|<0.01|
|[[:human_genes:U:UBA6|UBA6]]|3.12|<0.01|
|[[:human_genes:U:UBA5|UBA5]]|3.14|<0.01|
|[[:human_genes:H:HSPA14|HSPA14]]|3.39|<0.01|
|[[:human_genes:T:TRIP13|TRIP13]]|3.65|<0.01|
|[[:human_genes:U:UBR4|UBR4]]|3.81|<0.01|
|[[:human_genes:X:XPR1|XPR1]]|4.30|<0.01|
|[[:human_genes:C:CCNF|CCNF]]|4.31|<0.01|
|[[:human_genes:B:BUB1B|BUB1B]]|4.40|<0.01|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp97|BI-6727 0.0125μM R03 exp97]]|0.248|<button type="primary" size="small" modal="1">View</button>|
|[[:results:exp125|GSK461364A 0.005μM R03 exp125]]|0.129|<button type="primary" size="small" modal="2">View</button>|
|[[:results:exp103|Taxol 0.004μM R03 exp103]]|0.057|<button type="primary" size="small" modal="3">View</button>|
|[[:results:exp228|Demecolcine 0.03μM R05 exp228]]|0.056|<button type="primary" size="small" modal="4">View</button>|
|[[:results:exp190|Vincristine 0.0005μM R04 exp190]]|0.053|<button type="primary" size="small" modal="5">View</button>|
|[[:results:exp162|BI-D1870 2μM R04 exp162]]|0.051|<button type="primary" size="small" modal="6">View</button>|
</modal>


<modal id="1" size="lg" title="BI-2536 0.0042μM R03 exp95  vs  BI-6727 0.0125μM R03 exp97">
{{:chemogenomics:comparison_plots:exp95_vs_exp97.png?nolink |}}
</modal>

<modal id="2" size="lg" title="BI-2536 0.0042μM R03 exp95  vs  GSK461364A 0.005μM R03 exp125">
{{:chemogenomics:comparison_plots:exp125_vs_exp95.png?nolink |}}
</modal>

<modal id="3" size="lg" title="BI-2536 0.0042μM R03 exp95  vs  Taxol 0.004μM R03 exp103">
{{:chemogenomics:comparison_plots:exp103_vs_exp95.png?nolink |}}
</modal>

<modal id="4" size="lg" title="BI-2536 0.0042μM R03 exp95  vs  Demecolcine 0.03μM R05 exp228">
{{:chemogenomics:comparison_plots:exp228_vs_exp95.png?nolink |}}
</modal>

<modal id="5" size="lg" title="BI-2536 0.0042μM R03 exp95  vs  Vincristine 0.0005μM R04 exp190">
{{:chemogenomics:comparison_plots:exp190_vs_exp95.png?nolink |}}
</modal>

<modal id="6" size="lg" title="BI-2536 0.0042μM R03 exp95  vs  BI-D1870 2μM R04 exp162">
{{:chemogenomics:comparison_plots:exp162_vs_exp95.png?nolink |}}
</modal>



<modal id="modal_go_sensitive" size="lg" title="Top 30 sensitive GO terms">
^GO Term^Fold Change^Genes^
|dynactin complex|253.76|ACTR1A,DCTN2,ACTR1B|
|protein histidyl modification to diphthamide|236.84|DPH2,DPH1|
|inner kinetochore|174.15|CENPU,CENPL,CENPO,CENPN,CENPQ|
|protein depolymerization|46.75|KIF18A,STMN1,GAK|
|condensed chromosome, centromeric region|33.83|KIF18A,SKA1,CENPB,CENPU,DCTN2,CENPL,CENPO,CENPN,CENPQ,CCNB1|
|kinetochore|32.49|KIF18A,SKA1,CENPU,DCTN2,CENPL,CENPO,CENPN,CENPQ,CCNB1|
|metaphase chromosome alignment|30.76|KIF18A,DCTN2,CENPQ,CCNB1|
|chromosome, centromeric region|30.11|KIF18A,SKA1,CENPB,PDS5B,CENPU,DCTN2,CENPL,PPP2R5C,CENPO,CENPN,CENPQ,CCNB1|
|establishment of chromosome localization|27.22|KIF18A,DCTN2,CENPQ,CCNB1|
|chromosome localization|24.93|KIF18A,DCTN2,CENPQ,CCNB1|
|condensed chromosome|21.77|KIF18A,SKA1,CENPB,CENPU,DCTN2,CENPL,CENPO,CENPN,CENPQ,CCNB1|
|microtubule associated complex|20.56|KIF18A,ACTR1A,KIF15,DCTN2,ACTR1B|
|chromosomal region|19.00|KIF18A,SKA1,CENPB,PDS5B,CENPU,DCTN2,CENPL,PPP2R5C,CENPO,CENPN,CENPQ,CCNB1|
|chromosome segregation|16.25|KIF18A,SKA1,CENPU,DCTN2,CENPL,CENPO,CENPN,CENPQ,CCNB1|
|cell cycle process|8.82|KIF18A,STMN1,SKA1,PDS5B,CENPU,DCTN2,GIGYF2,CENPL,CENPO,LCMT1,CENPN,CENPQ,CCNB1|
|mitotic cell cycle|7.88|KIF18A,STMN1,SKA1,KIF15,DCTN2,GIGYF2,LCMT1,CCNB1|
|microtubule organizing center|5.87|KIF18A,SKA1,ACTR1A,CENPU,KIF15,DCTN2,ACTR1B,CCNB1|
</modal>
<modal id="modal_go_resistant" size="lg" title="Top 30 resistant GO terms">
^GO Term^Fold Change^Genes^
|protein K69-linked ufmylation|276.32|UBA5,UFL1|
|protein polyufmylation|276.32|UBA5,UFL1|
|viral translational termination-reinitiation|276.32|EIF3G,EIF3A|
|protein ufmylation|221.05|UBA5,UFL1|
|eukaryotic translation initiation factor 3 complex|118.42|EIF3J,EIF3G,EIF3A|
|eukaryotic 48S preinitiation complex|110.53|EIF3J,EIF3G,EIF3A|
|eukaryotic 43S preinitiation complex|97.52|EIF3J,EIF3G,EIF3A|
|translation preinitiation complex|97.52|EIF3J,EIF3G,EIF3A|
|cytoplasmic translation|24.67|EIF3J,EIF3G,RPS27A,EIF3A,RPL27|
|negative regulation of cell cycle|9.67|BUB1B,CCNF,TRIP13,MBTPS2,UFL1,HEXIM1|
|ribonucleoprotein complex|6.40|EIF3J,EIF3G,RPS27A,RBM5,EIF3A,HEXIM1,RPL27,ZNF622|
</modal>