GSK591 2.6μM R03 exp128 [The Human Chemical-Genetic Interaction Map Project]

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====== GSK591 2.6μM R03 exp128 ======
==== Mechanism of Action ====
Inhibits protein arginine methyltransferase PRMT5, inactive control is SGC2096
  * **<color #00a2e8>Class / Subclass 1:</color>** Gene Regulation / Epigenetic Inhibitor




==== Technical Notes ====
<accordion collapsed='true'>
<panel title='Compound References' collapsed='true'>
    * **<color #00a2e8>PubChem Name:</color>** %%2-(Cyclobutylamino)-N-[(2S)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]pyridine-4-carboxamide%%
    * **<color #00a2e8>Synonyms:</color>** EPZ015866; GSK3203591
    * **<color #00a2e8>CAS #:</color>** 1616391-87-7
    * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/117072552|117072552]]
    * **<color #00a2e8>IUPAC:</color>** %%2-(cyclobutylamino)-N-[(2S)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]pyridine-4-carboxamide%%
    * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C22H28N4O2/c27-20(15-26-11-9-16-4-1-2-5-18(16)14-26)13-24-22(28)17-8-10-23-21(12-17)25-19-6-3-7-19/h1-2,4-5,8,10,12,19-20,27H,3,6-7,9,11,13-15H2,(H,23,25)(H,24,28)/t20-/m0/s1
    * **<color #00a2e8>INCHI Key:</color>** TWKYXZSXXXKKJU-FQEVSTJZSA-N
    * **<color #00a2e8>Molecular Weight:</color>** 380.5
    * **<color #00a2e8>Canonical SMILES:</color>** C1CC(C1)NC2=NC=CC(=C2)C(=O)NCC(CN3CCC4=CC=CC=C4C3)O
    * **<color #00a2e8>Isomeric SMILES:</color>** C1CC(C1)NC2=NC=CC(=C2)C(=O)NC[C@@H](CN3CCC4=CC=CC=C4C3)O
    * **<color #00a2e8>Molecular Formula:</color>** C22H28N4O2
{{:chemogenomics:structures:chem-0080.svg?nolink}}
</panel>


<panel title='Compound Supplier' collapsed='true'>
    * **<color #00a2e8>Supplier Name:</color>** Structural Genomics Consortium
    * **<color #00a2e8>Catalog #:</color>** N/A
    * **<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 C22H28N4O2 381.2285; found 381.22927
</panel>


<panel title='Dose Response Curve' collapsed='true'>
    * **<color #00a2e8>Platform ID:</color>** GSK591
    * **<color #00a2e8>Min:</color>** 5.5317; **<color #00a2e8>Max:</color>** 37.8129
{{:chemogenomics:dose_response:dr_85.png?nolink&500 |}}
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|< 300px 100px 200px >|
^ IC   ^ Concentration (µM) ^
| IC10  |N/A    |
| IC20  |0.1740    |
| IC30  |3.3135    |
| IC40  |N/A    |
| IC50  |N/A    |
| 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>**: 2.6µM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 4.8
    * **<color #00a2e8>Numbers of reads</color>**: 13320156


==== 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^
|4/2|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/GSK591_2.6uM_Round-3_exp128.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="default" size="sm" modal="modal_go_resistant">View</button>|
<modal id='ScorePlot' size='lg' title='GSK591 2.6μM R03 exp128'>
{{:chemogenomics:cranks_plots:exp128.png?nolink}}
</modal>


<modal id="modal_hits" size="sm" title="Top 30 S/R Genes">
^Gene^CRANKS Score^FDR^
|[[:human_genes:K:KDSR|KDSR]]|-3.84|<0.01|
|[[:human_genes:Z:ZC3H14|ZC3H14]]|-2.86|0.04|
|[[:human_genes:P:PRPF4B|PRPF4B]]|-2.69|0.05|
|[[:human_genes:A:ARL1|ARL1]]|-2.69|0.04|
|[[:human_genes:S:SNRPB2|SNRPB2]]|-2.66|0.04|
|[[:human_genes:C:CSDE1|CSDE1]]|-2.59|0.08|
|[[:human_genes:Y:YPEL5|YPEL5]]|-2.55|0.05|
|[[:human_genes:P:PNKP|PNKP]]|-2.49|0.23|
|[[:human_genes:D:DSN1|DSN1]]|-2.48|0.10|
|[[:human_genes:R:RABGGTB|RABGGTB]]|-2.43|0.11|
|[[:human_genes:G:GTF2F2|GTF2F2]]|-2.40|0.12|
|[[:human_genes:H:HNRNPF|HNRNPF]]|-2.37|0.10|
|[[:human_genes:S:SNF8|SNF8]]|-2.34|0.16|
|[[:human_genes:B:BRD1|BRD1]]|-2.33|0.10|
|[[:human_genes:H:HEXIM1|HEXIM1]]|-2.31|0.11|
|[[:human_genes:V:VPS25|VPS25]]|-2.28|0.49|
|[[:human_genes:T:TSC2|TSC2]]|-2.26|0.20|
|[[:human_genes:M:MVD|MVD]]|-2.26|0.20|
|[[:human_genes:H:HIAT1|HIAT1]]|-2.24|0.30|
|[[:human_genes:P:PRKAG1|PRKAG1]]|-2.23|0.20|
|[[:human_genes:N:NSRP1|NSRP1]]|-2.22|0.20|
|[[:human_genes:A:ANKRD17|ANKRD17]]|-2.21|0.20|
|[[:human_genes:I:INO80|INO80]]|-2.20|0.30|
|[[:human_genes:M:MAPK14|MAPK14]]|-2.19|0.16|
|[[:human_genes:H:HDAC3|HDAC3]]|-2.10|0.49|
|[[:human_genes:G:GET4|GET4]]|-2.10|0.20|
|[[:human_genes:A:API5|API5]]|-2.09|0.20|
|[[:human_genes:K:KIF18A|KIF18A]]|-2.07|0.30|
|[[:human_genes:O:OR5R1|OR5R1]]|-2.05|0.30|
|[[:human_genes:A:ABCB1|ABCB1]]|-2.05|0.30|
|[[:human_genes:T:TCHP|TCHP]]|1.99|0.48|
|[[:human_genes:B:B4GALT6|B4GALT6]]|2.00|0.42|
|[[:human_genes:C:C10orf131|C10orf131]]|2.01|0.42|
|[[:human_genes:H:HARS2|HARS2]]|2.01|0.48|
|[[:human_genes:P:POLR3B|POLR3B]]|2.03|0.46|
|[[:human_genes:P:PCDHGB4|PCDHGB4]]|2.03|0.48|
|[[:human_genes:C:CEACAM3|CEACAM3]]|2.03|0.46|
|[[:human_genes:M:MRPL55|MRPL55]]|2.04|0.38|
|[[:human_genes:R:RBM25|RBM25]]|2.05|0.48|
|[[:human_genes:Z:ZNF622|ZNF622]]|2.06|0.51|
|[[:human_genes:P:PAF1|PAF1]]|2.06|0.51|
|[[:human_genes:M:MED13L|MED13L]]|2.09|0.42|
|[[:human_genes:T:TRMT44|TRMT44]]|2.10|0.31|
|[[:human_genes:R:RCOR1|RCOR1]]|2.10|0.31|
|[[:human_genes:A:AFF1|AFF1]]|2.11|0.49|
|[[:human_genes:S:SYVN1|SYVN1]]|2.12|0.48|
|[[:human_genes:P:PCYT2|PCYT2]]|2.16|0.26|
|[[:human_genes:R:RCC2|RCC2]]|2.17|0.26|
|[[:human_genes:R:REXO2|REXO2]]|2.17|0.38|
|[[:human_genes:P:PARP3|PARP3]]|2.18|0.26|
|[[:human_genes:A:ATP5B|ATP5B]]|2.25|0.26|
|[[:human_genes:S:SRM|SRM]]|2.26|0.26|
|[[:human_genes:P:POLR2J2|POLR2J2]]|2.26|0.61|
|[[:human_genes:C:COX10|COX10]]|2.30|0.26|
|[[:human_genes:C:CTPS1|CTPS1]]|2.35|0.48|
|[[:human_genes:T:TRAPPC12|TRAPPC12]]|2.45|0.12|
|[[:human_genes:U:USP39|USP39]]|2.45|0.26|
|[[:human_genes:C:CRIP2|CRIP2]]|2.53|0.11|
|[[:human_genes:P:PRPF40A|PRPF40A]]|2.83|0.05|
|[[:human_genes:T:TP53|TP53]]|2.91|0.05|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp290|LLY-283 2.6μM R06 exp290]]|0.089|<button type="primary" size="small" modal="1">View</button>|
|[[:results:exp312|2-Methoxyestradiol 0.55 to 1μM on day4 R07 exp312]]|0.054|<button type="primary" size="small" modal="2">View</button>|
</modal>


<modal id="1" size="lg" title="GSK591 2.6μM R03 exp128  vs  LLY-283 2.6μM R06 exp290">
{{:chemogenomics:comparison_plots:exp128_vs_exp290.png?nolink |}}
</modal>

<modal id="2" size="lg" title="2-Methoxyestradiol 0.55 to 1μM on day4 R07 exp312  vs  GSK591 2.6μM R03 exp128">
{{:chemogenomics:comparison_plots:exp128_vs_exp312.png?nolink |}}
</modal>



<modal id="modal_go_sensitive" size="lg" title="Top 30 sensitive GO terms">
^GO Term^Fold Change^Genes^
|ESCRT II complex|592.11|SNF8,VPS25|
|nuclear speck|10.18|ZC3H14,PRPF4B,SNRPB2,BRD1,NSRP1,MAPK14,API5|
|nuclear body|6.55|ZC3H14,PRPF4B,SNRPB2,DSN1,BRD1,NSRP1,INO80,MAPK14,API5|
</modal>
<modal id="modal_go_resistant" size="lg" title="Top 30 resistant GO terms">No GO term hits below threshold. (FDR <0.05)</modal>