====== GSK461364A 0.1μM R03 exp126 ======
==== Mechanism of Action ====
Inhibits PLK1
* **Class / Subclass 1:** Signal Transduction / Kinase Inhibitor
* **Class / Subclass 2:** Cell Cycle / Mitotic Inhibitor
==== Technical Notes ====
* **PubChem Name:** %%Gsk-461364%%
* **Synonyms:** GSK461364A
* **CAS #:** 929095-18-1
* **PubChem CID:** [[https://pubchem.ncbi.nlm.nih.gov/compound/15983966|15983966]]
* **IUPAC:** %%5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide%%
* **INCHI Name:** InChI=1S/C27H28F3N5O2S/c1-17(19-5-3-4-6-20(19)27(28,29)30)37-23-14-24(38-25(23)26(31)36)35-16-32-21-8-7-18(13-22(21)35)15-34-11-9-33(2)10-12-34/h3-8,13-14,16-17H,9-12,15H2,1-2H3,(H2,31,36)/t17-/m1/s1
* **INCHI Key:** ZHJGWYRLJUCMRT-QGZVFWFLSA-N
* **Molecular Weight:** 543.6
* **Canonical SMILES:** CC(C1=CC=CC=C1C(F)(F)F)OC2=C(SC(=C2)N3C=NC4=C3C=C(C=C4)CN5CCN(CC5)C)C(=O)N
* **Isomeric SMILES:** C[C@H](C1=CC=CC=C1C(F)(F)F)OC2=C(SC(=C2)N3C=NC4=C3C=C(C=C4)CN5CCN(CC5)C)C(=O)N
* **Molecular Formula:** C27H28F3N5O2S
{{:chemogenomics:structures:chem-0078.svg?nolink}}
* **Supplier Name:** Med Chem Express
* **Catalog #:** HY-50877
* **Lot #:** CS-0069-03047
* **HRMS (ESI-TOF) m/z:** (M+H)+ Calcd for C27H28F3N5O2S 544.19886; found 544.20114
* **Platform ID:** GSK461364A
* **Min:** 0.3593; **Max:** 95.3469
{{:chemogenomics:dose_response:dr_83.png?nolink&500 |}}
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^ IC ^ Concentration (µM) ^
| IC10 |N/A |
| IC20 |N/A |
| IC30 |0.0022 |
| IC40 |0.0102 |
| IC50 |0.0421 |
| IC60 |N/A |
| IC70 |N/A |
| IC80 |N/A |
| IC90 |N/A |
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==== Screen Summary ====
* **Round**: 03
* **Dose**: 100nM
* **Days of incubation**: 8
* **Doublings**: -0.0
* **Numbers of reads**: 21491358
==== 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^
|1/18|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/GSK461364A_0.1uM_Round-3_exp126.txt|Scores]]||||||
{{:chemogenomics:cranks_plots:exp126.png?nolink}}
^Gene^CRANKS Score^FDR^
|[[:human_genes:P:PDS5B|PDS5B]]|-3.12|<0.01|
|[[:human_genes:S:SCFD1|SCFD1]]|-2.89|0.29|
|[[:human_genes:S:SPTB|SPTB]]|-2.68|0.06|
|[[:human_genes:C:CDC20|CDC20]]|-2.66|0.46|
|[[:human_genes:G:GAGE2A|GAGE2A]]|-2.58|0.59|
|[[:human_genes:P:PNO1|PNO1]]|-2.42|0.48|
|[[:human_genes:P:POLA2|POLA2]]|-2.29|0.59|
|[[:human_genes:P:POLR2L|POLR2L]]|-2.28|0.48|
|[[:human_genes:V:VPS25|VPS25]]|-2.28|0.48|
|[[:human_genes:E:ELOVL7|ELOVL7]]|-2.27|0.39|
|[[:human_genes:N:NUP93|NUP93]]|-2.26|0.48|
|[[:human_genes:C:COPE|COPE]]|-2.25|0.63|
|[[:human_genes:P:PSMC3|PSMC3]]|-2.24|0.48|
|[[:human_genes:S:SLC24A1|SLC24A1]]|-2.21|0.46|
|[[:human_genes:T:TTK|TTK]]|-2.21|0.48|
|[[:human_genes:V:VPS37B|VPS37B]]|-2.20|0.46|
|[[:human_genes:R:RPSA|RPSA]]|-2.20|0.60|
|[[:human_genes:V:VPS28|VPS28]]|-2.19|0.48|
|[[:human_genes:M:MCM5|MCM5]]|-2.18|0.60|
|[[:human_genes:A:ASGR1|ASGR1]]|-2.17|0.46|
|[[:human_genes:P:PKD2|PKD2]]|-2.17|0.46|
|[[:human_genes:K:KCNA3|KCNA3]]|-2.16|0.46|
|[[:human_genes:Y:YTHDC1|YTHDC1]]|-2.16|0.61|
|[[:human_genes:S:SART1|SART1]]|-2.13|0.65|
|[[:human_genes:D:DSC1|DSC1]]|-2.11|0.46|
|[[:human_genes:S:SRSF2|SRSF2]]|-2.11|0.59|
|[[:human_genes:P:PLK1|PLK1]]|-2.07|0.59|
|[[:human_genes:P:PLD1|PLD1]]|-2.07|0.46|
|[[:human_genes:G:GOLGA8H|GOLGA8H]]|-2.03|0.59|
|[[:human_genes:Z:ZFAND5|ZFAND5]]|-2.03|0.46|
|[[:human_genes:C:CCDC82|CCDC82]]|2.32|0.08|
|[[:human_genes:P:POLR3H|POLR3H]]|2.33|0.12|
|[[:human_genes:E:ENY2|ENY2]]|2.34|0.08|
|[[:human_genes:M:MED16|MED16]]|2.36|0.11|
|[[:human_genes:A:ALG2|ALG2]]|2.39|0.06|
|[[:human_genes:R:RBM14-RBM4|RBM14-RBM4]]|2.40|0.10|
|[[:human_genes:R:RBM14|RBM14]]|2.42|0.09|
|[[:human_genes:G:GFPT1|GFPT1]]|2.45|0.08|
|[[:human_genes:G:GTF3C4|GTF3C4]]|2.46|0.06|
|[[:human_genes:S:SPG21|SPG21]]|2.47|0.03|
|[[:human_genes:G:GTF3A|GTF3A]]|2.47|0.03|
|[[:human_genes:A:ATP5O|ATP5O]]|2.52|0.03|
|[[:human_genes:T:TRIAP1|TRIAP1]]|2.52|0.04|
|[[:human_genes:A:ATP2A2|ATP2A2]]|2.54|0.27|
|[[:human_genes:K:KCTD5|KCTD5]]|2.58|0.02|
|[[:human_genes:R:RTCB|RTCB]]|2.58|0.06|
|[[:human_genes:T:TOP1|TOP1]]|2.68|0.03|
|[[:human_genes:G:GTF2A2|GTF2A2]]|2.71|0.04|
|[[:human_genes:R:RPP21|RPP21]]|2.75|0.02|
|[[:human_genes:A:ATP5B|ATP5B]]|2.77|0.01|
|[[:human_genes:M:MBTPS2|MBTPS2]]|2.80|0.01|
|[[:human_genes:R:ROMO1|ROMO1]]|2.86|0.01|
|[[:human_genes:G:GMPPB|GMPPB]]|2.94|0.04|
|[[:human_genes:P:PYROXD1|PYROXD1]]|3.04|0.06|
|[[:human_genes:D:DPAGT1|DPAGT1]]|3.12|0.01|
|[[:human_genes:P:PELO|PELO]]|3.34|<0.01|
|[[:human_genes:B:BUB3|BUB3]]|3.45|0.01|
|[[:human_genes:T:THG1L|THG1L]]|3.55|<0.01|
|[[:human_genes:T:TRMT10A|TRMT10A]]|3.74|<0.01|
|[[:human_genes:T:TAZ|TAZ]]|3.76|0.01|
^Screen^Correlation^Plot^
|[[:results:exp108|Vinblastine 0.2μM R03 exp108]]|0.141||
|[[:results:exp22|MLN-4924 2μM R00 exp22]]|0.096||
|[[:results:exp443|SNS-032 15μM R08 exp443]]|0.081||
|[[:results:exp487|Hinokiflavone 12μM R08 exp487]]|0.074||
|[[:results:exp515|PU-H71 1μM R08 exp515]]|0.07||
|[[:results:exp111|R-DABN 8μM R03 exp111]]|0.064||
|[[:results:exp28|Pimelic-diphenylamide-106 5μM R00 exp28]]|0.062||
|[[:results:exp531|THZ1 0.06μM R08 exp531]]|0.062||
|[[:results:exp135|MS023 7μM R03 exp135]]|0.06||
|[[:results:exp94|Nocodazole 0.1μM R03 exp94]]|0.06||
|[[:results:exp503|Mitomycin-C 0.06μM R08 exp503]]|0.057||
|[[:results:exp64|Nocodazole 0.2μM R02 exp64]]|0.052||
|[[:results:exp106|UM131593 0.2μM R03 exp106]]|0.052||
|[[:results:exp96|BI-2536 0.02μM R03 exp96]]|0.175||
|[[:results:exp98|BI-6727 0.04μM R03 exp98]]|0.157||
|[[:results:exp539|42°C R08 exp539]]|0.09||
|[[:results:exp459|Bleomycin 5μM R08 exp459]]|0.087||
|[[:results:exp93|DABN racemic mixture R03 exp93]]|0.085||
|[[:results:exp448|Ammonium tetrathiomolybdate 10μM R08 exp448]]|0.078||
|[[:results:exp472|CI-1040 9.5μM R08 exp472]]|0.073||
|[[:results:exp451|Atovaquone 15μM R08 exp451]]|0.07||
|[[:results:exp2|5-Fluorouracil 20μM R00 exp2]]|0.068||
|[[:results:exp456|Benzoate 20000μM R08 exp456]]|0.065||
|[[:results:exp440|Aphidicolin 0.4μM R08 exp440]]|0.064||
|[[:results:exp3|Actinomycin-D 0.001μM R00 exp3]]|0.064||
|[[:results:exp478|Doxorubicin 0.02μM R08 exp478]]|0.062||
|[[:results:exp19|Etoposide 1μM R00 exp19]]|0.062||
|[[:results:exp17|DABN 20μM R00 exp17]]|0.057||
|[[:results:exp7|Bortezomib 0.05μM R00 exp7]]|0.055||
|[[:results:exp199|Etoposide 0.3μM R05 exp199]]|0.052||
{{:chemogenomics:comparison_plots:exp108_vs_exp126.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp22.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp443.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp487.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp515.png?nolink |}}
{{:chemogenomics:comparison_plots:exp111_vs_exp126.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp28.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp531.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp135.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp94.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp503.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp64.png?nolink |}}
{{:chemogenomics:comparison_plots:exp106_vs_exp126.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp96.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp98.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp539.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp459.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp93.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp448.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp472.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp451.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp2.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp456.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp440.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp3.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp478.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp19.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp17.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp7.png?nolink |}}
{{:chemogenomics:comparison_plots:exp126_vs_exp199.png?nolink |}}
^GO Term^Fold Change^Genes^
|regulation of anaphase-promoting complex-dependent catabolic process|296.07|CDC20,PLK1|
|female meiosis chromosome segregation|296.07|TTK,PLK1|
|protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway|126.89|VPS25,VPS37B,VPS28|
|mitotic spindle assembly checkpoint signaling|63.44|CDC20,TTK,PLK1|
|spindle checkpoint signaling|61.26|CDC20,TTK,PLK1|
|multivesicular body assembly|59.21|VPS25,VPS37B,VPS28|
|negative regulation of sister chromatid segregation|57.30|CDC20,TTK,PLK1|
|multivesicular body organization|57.30|VPS25,VPS37B,VPS28|
|negative regulation of mitotic sister chromatid separation|57.30|CDC20,TTK,PLK1|
|negative regulation of mitotic metaphase/anaphase transition|57.30|CDC20,TTK,PLK1|
|negative regulation of chromosome separation|53.83|CDC20,TTK,PLK1|
|negative regulation of chromosome segregation|53.83|CDC20,TTK,PLK1|
|late endosome to vacuole transport|52.25|VPS25,VPS37B,VPS28|
|ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway|50.76|VPS25,VPS37B,VPS28|
|endosome transport via multivesicular body sorting pathway|45.55|VPS25,VPS37B,VPS28|
|negative regulation of mitotic nuclear division|45.55|CDC20,TTK,PLK1|
^GO Term^Fold Change^Genes^
|GDP-mannose biosynthetic process|368.44|GMPPB,PMM2|
|proton-transporting ATP synthase complex, catalytic core F(1)|221.07|ATP5F1B,ATP5PO|
|nucleotide-sugar biosynthetic process|97.53|GMPPB,GFPT1,PMM2|
|nucleotide-sugar metabolic process|51.81|DPAGT1,GMPPB,PMM2|
|transcription by RNA polymerase III|43.63|GTF3A,GTF3C4,POLR3H|
|protein N-linked glycosylation|32.04|DPAGT1,GFPT1,ALG2,PMM2|
|DNA-templated transcription initiation|21.67|GTF2A2,GTF3C4,MED16,POLR3H|
|tRNA metabolic process|17.64|TRMT10A,THG1L,RPP21,RTCB,GTF3C4,YARS1|
|protein glycosylation|14.94|DPAGT1,GMPPB,GFPT1,ALG2,PMM2|
|macromolecule glycosylation|14.94|DPAGT1,GMPPB,GFPT1,ALG2,PMM2|
|glycosylation|13.29|DPAGT1,GMPPB,GFPT1,ALG2,PMM2|
|ncRNA metabolic process|8.74|TRMT10A,THG1L,PELO,RPP21,RTCB,GTF3A,GTF3C4,YARS1|
|nucleobase-containing compound biosynthetic process|7.31|GMPPB,ATP5F1B,GTF2A2,ATP5PO,GTF3A,GTF3C4,GFPT1,MED16,ENY2,POLR3H,PMM2|
|carbohydrate derivative biosynthetic process|6.97|DPAGT1,GMPPB,ATP5F1B,ATP5PO,GFPT1,ALG2,PMM2|
|heterocycle biosynthetic process|6.70|GMPPB,ATP5F1B,GTF2A2,ATP5PO,GTF3A,GTF3C4,GFPT1,MED16,ENY2,POLR3H,PMM2|
|aromatic compound biosynthetic process|6.64|GMPPB,ATP5F1B,GTF2A2,ATP5PO,GTF3A,GTF3C4,GFPT1,MED16,ENY2,POLR3H,PMM2|