====== TIC10 10μM R08 exp532 ======
==== Mechanism of Action ====
Inhibits mitochondrial CLPP protease, a.k.a. ONC201, parent of ONC212, possible agonist of GPR132
  * **<color #00a2e8>Class / Subclass 1:</color>** Proteostasis / Protease Inhibitor
  * **<color #00a2e8>Class / Subclass 2:</color>** Signal Transduction / GPCR Agonist



==== Technical Notes ====
<accordion collapsed='true'>
<panel title='Compound References' collapsed='true'>
    * **<color #00a2e8>PubChem Name:</color>** %%7-Benzyl-4-(2-methylbenzyl)-1,2,6,7,8,9-hexahydroimidazo[1,2-A]pyrido[3,4-E]pyrimidin-5(4H)-one%%
    * **<color #00a2e8>Synonyms:</color>** ONC-201
    * **<color #00a2e8>CAS #:</color>** 1616632-77-9
    * **<color #00a2e8>PubChem CID:</color>** [[https://pubchem.ncbi.nlm.nih.gov/compound/73777259|73777259]]
    * **<color #00a2e8>IUPAC:</color>** %%11-benzyl-7-[(2-methylphenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5-dien-8-one%%
    * **<color #00a2e8>INCHI Name:</color>** InChI=1S/C24H26N4O/c1-18-7-5-6-10-20(18)16-28-23(29)21-17-26(15-19-8-3-2-4-9-19)13-11-22(21)27-14-12-25-24(27)28/h2-10H,11-17H2,1H3
    * **<color #00a2e8>INCHI Key:</color>** VLULRUCCHYVXOH-UHFFFAOYSA-N
    * **<color #00a2e8>Molecular Weight:</color>** 386.5
    * **<color #00a2e8>Canonical SMILES:</color>** CC1=CC=CC=C1CN2C(=O)C3=C(CCN(C3)CC4=CC=CC=C4)N5C2=NCC5
    * **<color #00a2e8>Isomeric SMILES:</color>** N/A
    * **<color #00a2e8>Molecular Formula:</color>** C24H26N4O
{{:chemogenomics:structures:chem-0336.svg?nolink}}
</panel>


<panel title='Compound Supplier' collapsed='true'>
    * **<color #00a2e8>Supplier Name:</color>** Med Chem Express
    * **<color #00a2e8>Catalog #:</color>** HY-15615A
    * **<color #00a2e8>Lot #:</color>** 14564
</panel>


<panel title='Compound Characterization' collapsed='true'>
    * **<color #00a2e8>HRMS (ESI-TOF) m/z:</color>** (M+H)+ Calcd for C24H26N4O 387.21794; found 387.22085
</panel>


<panel title='Dose Response Curve' collapsed='true'>
    * **<color #00a2e8>Platform ID:</color>** TIC10
    * **<color #00a2e8>Min:</color>** 0.7077; **<color #00a2e8>Max:</color>** 65.9742
{{:chemogenomics:dose_response:dr_589.png?nolink&500 |}}
\\ 
\\ 
\\ 
\\ 
|< 300px 100px 200px >|
^ IC   ^ Concentration (µM) ^
| IC10  |0.0216    |
| IC20  |0.2196    |
| IC30  |1.0240    |
| IC40  |3.6190    |
| IC50  |11.5200    |
| IC60  |36.7000    |
| IC70  |N/A    |
| IC80  |N/A    |
| IC90  |N/A    |
\\ 
</panel>
</accordion>
==== Screen Summary ====
    * **<color #00a2e8>Round</color>**: 08
    * **<color #00a2e8>Dose</color>**: 10µM
    * **<color #00a2e8>Days of incubation</color>**: 8
    * **<color #00a2e8>Doublings</color>**: 0.8
    * **<color #00a2e8>Numbers of reads</color>**: 15670063


==== 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^
|0/12|<color #e85500>[[https://files.tyerslab.com/files/public/chemogenomics/cranks/TIC10_10uM_Round-8_exp532.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="default" 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='TIC10 10μM R08 exp532'>
{{:chemogenomics:cranks_plots:exp532.png?nolink}}
</modal>


<modal id="modal_hits" size="sm" title="Top 30 S/R Genes">
^Gene^CRANKS Score^FDR^
|[[:human_genes:O:OTUB1|OTUB1]]|-2.73|0.17|
|[[:human_genes:T:TCF3|TCF3]]|-2.72|0.24|
|[[:human_genes:Z:ZBED2|ZBED2]]|-2.58|0.35|
|[[:human_genes:Z:ZNF292|ZNF292]]|-2.52|0.17|
|[[:human_genes:A:ATP6V0B|ATP6V0B]]|-2.52|0.45|
|[[:human_genes:N:NPIPB8|NPIPB8]]|-2.47|0.35|
|[[:human_genes:X:XYLT2|XYLT2]]|-2.32|0.35|
|[[:human_genes:M:MYLIP|MYLIP]]|-2.31|0.35|
|[[:human_genes:R:RPL8|RPL8]]|-2.30|0.60|
|[[:human_genes:C:CDC73|CDC73]]|-2.30|0.35|
|[[:human_genes:C:CACNA1D|CACNA1D]]|-2.26|0.35|
|[[:human_genes:S:STK25|STK25]]|-2.24|0.35|
|[[:human_genes:B:BCOR|BCOR]]|-2.21|0.35|
|[[:human_genes:C:CD8A|CD8A]]|-2.17|0.35|
|[[:human_genes:G:GKN1|GKN1]]|-2.15|0.35|
|[[:human_genes:U:UCMA|UCMA]]|-2.14|0.35|
|[[:human_genes:Z:ZDHHC16|ZDHHC16]]|-2.14|0.35|
|[[:human_genes:P:PSMD13|PSMD13]]|-2.12|0.35|
|[[:human_genes:P:POLD3|POLD3]]|-2.12|0.63|
|[[:human_genes:R:RNF2|RNF2]]|-2.07|0.35|
|[[:human_genes:C:CTR9|CTR9]]|-2.07|0.35|
|[[:human_genes:I:ISCU|ISCU]]|-2.05|0.55|
|[[:human_genes:S:SMU1|SMU1]]|-2.05|0.44|
|[[:human_genes:C:CTNNBL1|CTNNBL1]]|-2.05|0.35|
|[[:human_genes:A:ACP1|ACP1]]|-2.05|0.35|
|[[:human_genes:O:ORC1|ORC1]]|-2.04|0.38|
|[[:human_genes:P:POLE2|POLE2]]|-2.04|0.55|
|[[:human_genes:G:GPX4|GPX4]]|-2.02|0.35|
|[[:human_genes:E:ESPL1|ESPL1]]|-2.01|0.53|
|[[:human_genes:V:VPS25|VPS25]]|-2.00|0.60|
|[[:human_genes:S:SRD5A3|SRD5A3]]|2.21|0.10|
|[[:human_genes:M:MRPS33|MRPS33]]|2.21|0.18|
|[[:human_genes:P:PTAR1|PTAR1]]|2.22|0.14|
|[[:human_genes:A:ATP5J|ATP5J]]|2.27|0.09|
|[[:human_genes:N:N6AMT1|N6AMT1]]|2.27|0.20|
|[[:human_genes:E:E2F8|E2F8]]|2.29|0.11|
|[[:human_genes:C:COX7B|COX7B]]|2.30|0.16|
|[[:human_genes:S:SARS2|SARS2]]|2.32|0.15|
|[[:human_genes:F:FASTKD5|FASTKD5]]|2.32|0.11|
|[[:human_genes:G:GFPT1|GFPT1]]|2.35|0.14|
|[[:human_genes:H:HCCS|HCCS]]|2.36|0.14|
|[[:human_genes:E:ENY2|ENY2]]|2.37|0.09|
|[[:human_genes:B:BCS1L|BCS1L]]|2.38|0.05|
|[[:human_genes:H:HSD17B10|HSD17B10]]|2.38|0.09|
|[[:human_genes:G:GATC|GATC]]|2.38|0.05|
|[[:human_genes:P:PTDSS1|PTDSS1]]|2.40|0.05|
|[[:human_genes:D:DARS2|DARS2]]|2.42|0.22|
|[[:human_genes:T:TRMT10A|TRMT10A]]|2.44|0.04|
|[[:human_genes:G:GEMIN7|GEMIN7]]|2.44|0.04|
|[[:human_genes:T:TRIP12|TRIP12]]|2.48|0.04|
|[[:human_genes:M:MARCH5|MARCH5]]|2.51|0.05|
|[[:human_genes:C:COX16|COX16]]|2.57|0.03|
|[[:human_genes:C:C12orf65|C12orf65]]|2.58|0.03|
|[[:human_genes:R:RNASEH1|RNASEH1]]|2.63|0.03|
|[[:human_genes:D:DPAGT1|DPAGT1]]|2.69|0.04|
|[[:human_genes:K:KIAA0391|KIAA0391]]|2.78|0.03|
|[[:human_genes:C:CEPT1|CEPT1]]|2.80|0.01|
|[[:human_genes:M:MBTPS2|MBTPS2]]|3.38|<0.01|
|[[:human_genes:C:CLPP|CLPP]]|6.19|<0.01|
|[[:human_genes:M:MIPEP|MIPEP]]|6.25|<0.01|
</modal>


<modal id="modal_screen_similarity" size="lg" title="Correlated Screens">
^Screen^Correlation^Plot^
|[[:results:exp527|Tanespimycin 14μM R08 exp527]]|0.112|<button type="primary" size="small" modal="1">View</button>|
|[[:results:exp529|Thimerosal 0.85μM R08 exp529]]|0.085|<button type="primary" size="small" modal="2">View</button>|
|[[:results:exp108|Vinblastine 0.2μM R03 exp108]]|0.051|<button type="primary" size="small" modal="3">View</button>|
|[[:results:exp513|ONC212 0.15μM R08 exp513]]|0.145|<button type="primary" size="small" modal="4">View</button>|
|[[:results:exp441|GSK-J4 1.5μM R08 exp441]]|0.111|<button type="primary" size="small" modal="5">View</button>|
|[[:results:exp503|Mitomycin-C 0.06μM R08 exp503]]|0.11|<button type="primary" size="small" modal="6">View</button>|
|[[:results:exp472|CI-1040 9.5μM R08 exp472]]|0.089|<button type="primary" size="small" modal="7">View</button>|
|[[:results:exp515|PU-H71 1μM R08 exp515]]|0.083|<button type="primary" size="small" modal="8">View</button>|
|[[:results:exp329|Hydroxyurea 100μM R07 exp329]]|0.078|<button type="primary" size="small" modal="9">View</button>|
|[[:results:exp435|JQ1 0.8μM R08 exp435]]|0.076|<button type="primary" size="small" modal="10">View</button>|
|[[:results:exp474|CR131-b 0.005μM R08 exp474]]|0.074|<button type="primary" size="small" modal="11">View</button>|
|[[:results:exp451|Atovaquone 15μM R08 exp451]]|0.074|<button type="primary" size="small" modal="12">View</button>|
|[[:results:exp448|Ammonium tetrathiomolybdate 10μM R08 exp448]]|0.07|<button type="primary" size="small" modal="13">View</button>|
|[[:results:exp440|Aphidicolin 0.4μM R08 exp440]]|0.066|<button type="primary" size="small" modal="14">View</button>|
|[[:results:exp431|Rotenone 0.07μM R08 exp431]]|0.066|<button type="primary" size="small" modal="15">View</button>|
|[[:results:exp531|THZ1 0.06μM R08 exp531]]|0.06|<button type="primary" size="small" modal="16">View</button>|
|[[:results:exp350|Deferoxamine 11μM R07 exp350]]|0.06|<button type="primary" size="small" modal="17">View</button>|
|[[:results:exp502|Milciclib 2μM R08 exp502]]|0.06|<button type="primary" size="small" modal="18">View</button>|
|[[:results:exp487|Hinokiflavone 12μM R08 exp487]]|0.06|<button type="primary" size="small" modal="19">View</button>|
|[[:results:exp447|Amiloride 100μM R08 exp447]]|0.055|<button type="primary" size="small" modal="20">View</button>|
|[[:results:exp478|Doxorubicin 0.02μM R08 exp478]]|0.051|<button type="primary" size="small" modal="21">View</button>|
|[[:results:exp346|CoCl2 18μM R07 exp346]]|0.051|<button type="primary" size="small" modal="22">View</button>|
</modal>


<modal id="1" size="lg" title="TIC10 10μM R08 exp532  vs  Tanespimycin 14μM R08 exp527">
{{:chemogenomics:comparison_plots:exp527_vs_exp532.png?nolink |}}
</modal>

<modal id="2" size="lg" title="TIC10 10μM R08 exp532  vs  Thimerosal 0.85μM R08 exp529">
{{:chemogenomics:comparison_plots:exp529_vs_exp532.png?nolink |}}
</modal>

<modal id="3" size="lg" title="TIC10 10μM R08 exp532  vs  Vinblastine 0.2μM R03 exp108">
{{:chemogenomics:comparison_plots:exp108_vs_exp532.png?nolink |}}
</modal>

<modal id="4" size="lg" title="ONC212 0.15μM R08 exp513  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp513_vs_exp532.png?nolink |}}
</modal>

<modal id="5" size="lg" title="GSK-J4 1.5μM R08 exp441  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp441_vs_exp532.png?nolink |}}
</modal>

<modal id="6" size="lg" title="Mitomycin-C 0.06μM R08 exp503  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp503_vs_exp532.png?nolink |}}
</modal>

<modal id="7" size="lg" title="CI-1040 9.5μM R08 exp472  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp472_vs_exp532.png?nolink |}}
</modal>

<modal id="8" size="lg" title="PU-H71 1μM R08 exp515  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp515_vs_exp532.png?nolink |}}
</modal>

<modal id="9" size="lg" title="Hydroxyurea 100μM R07 exp329  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp329_vs_exp532.png?nolink |}}
</modal>

<modal id="10" size="lg" title="JQ1 0.8μM R08 exp435  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp435_vs_exp532.png?nolink |}}
</modal>

<modal id="11" size="lg" title="CR131-b 0.005μM R08 exp474  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp474_vs_exp532.png?nolink |}}
</modal>

<modal id="12" size="lg" title="Atovaquone 15μM R08 exp451  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp451_vs_exp532.png?nolink |}}
</modal>

<modal id="13" size="lg" title="Ammonium tetrathiomolybdate 10μM R08 exp448  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp448_vs_exp532.png?nolink |}}
</modal>

<modal id="14" size="lg" title="Aphidicolin 0.4μM R08 exp440  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp440_vs_exp532.png?nolink |}}
</modal>

<modal id="15" size="lg" title="Rotenone 0.07μM R08 exp431  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp431_vs_exp532.png?nolink |}}
</modal>

<modal id="16" size="lg" title="THZ1 0.06μM R08 exp531  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp531_vs_exp532.png?nolink |}}
</modal>

<modal id="17" size="lg" title="Deferoxamine 11μM R07 exp350  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp350_vs_exp532.png?nolink |}}
</modal>

<modal id="18" size="lg" title="Milciclib 2μM R08 exp502  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp502_vs_exp532.png?nolink |}}
</modal>

<modal id="19" size="lg" title="Hinokiflavone 12μM R08 exp487  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp487_vs_exp532.png?nolink |}}
</modal>

<modal id="20" size="lg" title="Amiloride 100μM R08 exp447  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp447_vs_exp532.png?nolink |}}
</modal>

<modal id="21" size="lg" title="Doxorubicin 0.02μM R08 exp478  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp478_vs_exp532.png?nolink |}}
</modal>

<modal id="22" size="lg" title="CoCl2 18μM R07 exp346  vs  TIC10 10μM R08 exp532">
{{:chemogenomics:comparison_plots:exp346_vs_exp532.png?nolink |}}
</modal>



<modal id="modal_go_sensitive" size="lg" title="Top 30 sensitive GO terms">No GO term hits below threshold. (FDR <0.05)</modal>
<modal id="modal_go_resistant" size="lg" title="Top 30 resistant GO terms">
^GO Term^Fold Change^Genes^
|mitochondrial tRNA 5-end processing|552.30|PRORP,HSD17B10|
|mitochondrial RNA 5-end processing|368.20|PRORP,HSD17B10|
|mitochondrial RNA processing|82.85|PRORP,HSD17B10,FASTKD5|
|phosphotransferase activity, for other substituted phosphate groups|78.90|CEPT1,DPAGT1,PTDSS1|
|mitochondrial RNA metabolic process|51.38|DARS2,HSD17B10,FASTKD5,SARS2|
|cytochrome complex assembly|48.73|COX16,BCS1L,HCCS|
|mitochondrial gene expression|27.81|PRORP,DARS2,GATC,HSD17B10,FASTKD5,SARS2,MRPS33|
|catalytic activity, acting on a tRNA|22.09|PRORP,TRMT10A,DARS2,GATC,SARS2|
|tRNA metabolic process|17.82|PRORP,TRMT10A,DARS2,GATC,HSD17B10,SARS2|
|mitochondrial protein-containing complex|12.09|PRORP,HSD17B10,BCS1L,COX7B,ATP5PF,MRPS33|
|mitochondrial matrix|9.32|MIPEP,CLPP,PRORP,DARS2,HSD17B10,FASTKD5,SARS2,MRPS33|
</modal>