====== Rotenone 2μM R00 exp33 ======
==== Mechanism of Action ====
Inhibits complex I, blocks electron transfer from iron-sulfur centers to ubiquinone, generates ROS, also inhibits microtubule assembly
* **Class / Subclass 1:** Organelle Function / Mitochondrial Inhibitor
* **Class / Subclass 2:** Cell Cycle / Microtubule Poison
==== Technical Notes ====
* **PubChem Name:** %%Rotenone%%
* **Synonyms:** N/A
* **CAS #:** 83-79-4
* **PubChem CID:** [[https://pubchem.ncbi.nlm.nih.gov/compound/6758|6758]]
* **IUPAC:** %%(1S,6R,13S)-16,17-dimethoxy-6-prop-1-en-2-yl-2,7,20-trioxapentacyclo[11.8.0.03,11.04,8.014,19]henicosa-3(11),4(8),9,14,16,18-hexaen-12-one%%
* **INCHI Name:** InChI=1S/C23H22O6/c1-11(2)16-8-14-15(28-16)6-5-12-22(24)21-13-7-18(25-3)19(26-4)9-17(13)27-10-20(21)29-23(12)14/h5-7,9,16,20-21H,1,8,10H2,2-4H3/t16-,20-,21+/m1/s1
* **INCHI Key:** JUVIOZPCNVVQFO-HBGVWJBISA-N
* **Molecular Weight:** 394.4
* **Canonical SMILES:** CC(=C)C1CC2=C(O1)C=CC3=C2OC4COC5=CC(=C(C=C5C4C3=O)OC)OC
* **Isomeric SMILES:** CC(=C)[C@H]1CC2=C(O1)C=CC3=C2O[C@@H]4COC5=CC(=C(C=C5[C@@H]4C3=O)OC)OC
* **Molecular Formula:** C23H22O6
{{:chemogenomics:structures:chem-0018.svg?nolink}}
* **Supplier Name:** Sigma-Aldrich
* **Catalog #:** R8875
* **Lot #:** SLBG7568V
* **HRMS (ESI-TOF) m/z:** (M+H)+ Calcd for C23H22O6 395.14891; found 395.15075
* **Platform ID:** Rotenone
* **Min:** 11.0154; **Max:** 87.2842
{{:chemogenomics:dose_response:dr_275.png?nolink&500 |}}
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^ IC ^ Concentration (µM) ^
| IC10 |N/A |
| IC20 |0.0123 |
| IC30 |0.0322 |
| IC40 |0.0711 |
| IC50 |0.1468 |
| IC60 |N/A |
| IC70 |N/A |
| IC80 |N/A |
| IC90 |N/A |
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==== Screen Summary ====
* **Round**: 00
* **Dose**: 2µM
* **Days of incubation**: 8
* **Doublings**: 0.3
* **Numbers of reads**: 11335210
==== 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^
|7/173|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Rotenone_2uM_Round-0_exp33.txt|Scores]]||||||
{{:chemogenomics:cranks_plots:exp33.png?nolink}}
^Gene^CRANKS Score^FDR^
|[[:human_genes:S:SEPHS2|SEPHS2]]|-3.26|<0.01|
|[[:human_genes:A:ATP6AP1|ATP6AP1]]|-3.17|0.28|
|[[:human_genes:D:DDX3X|DDX3X]]|-3.05|<0.01|
|[[:human_genes:P:PSTK|PSTK]]|-2.92|0.02|
|[[:human_genes:C:COX7A2L|COX7A2L]]|-2.89|0.01|
|[[:human_genes:A:ATP6V0C|ATP6V0C]]|-2.61|0.48|
|[[:human_genes:B:BRD2|BRD2]]|-2.57|0.05|
|[[:human_genes:H:HNRNPA0|HNRNPA0]]|-2.54|0.05|
|[[:human_genes:A:ATP6V1A|ATP6V1A]]|-2.53|0.09|
|[[:human_genes:Y:YPEL5|YPEL5]]|-2.53|0.05|
|[[:human_genes:A:ATP6V1B2|ATP6V1B2]]|-2.48|0.09|
|[[:human_genes:R:RAB43|RAB43]]|-2.45|0.10|
|[[:human_genes:G:GZF1|GZF1]]|-2.43|0.17|
|[[:human_genes:T:TSC2|TSC2]]|-2.39|0.09|
|[[:human_genes:M:MTCH2|MTCH2]]|-2.35|0.09|
|[[:human_genes:P:POLE|POLE]]|-2.34|0.48|
|[[:human_genes:M:MRS2|MRS2]]|-2.34|0.09|
|[[:human_genes:S:SLC6A12|SLC6A12]]|-2.33|0.14|
|[[:human_genes:A:AATF|AATF]]|-2.32|0.28|
|[[:human_genes:E:EEFSEC|EEFSEC]]|-2.29|0.10|
|[[:human_genes:P:PCGF1|PCGF1]]|-2.28|0.10|
|[[:human_genes:S:SLC6A17|SLC6A17]]|-2.25|0.11|
|[[:human_genes:C:CLSPN|CLSPN]]|-2.24|0.29|
|[[:human_genes:B:BIRC5|BIRC5]]|-2.24|0.28|
|[[:human_genes:T:TAF1|TAF1]]|-2.23|0.28|
|[[:human_genes:U:UIMC1|UIMC1]]|-2.21|0.20|
|[[:human_genes:A:ANKRD13C|ANKRD13C]]|-2.18|0.32|
|[[:human_genes:F:FBXL14|FBXL14]]|-2.15|0.17|
|[[:human_genes:Y:YY1|YY1]]|-2.11|0.28|
|[[:human_genes:S:SCGB1C1|SCGB1C1]]|-2.10|0.20|
|[[:human_genes:D:DPY19L1|DPY19L1]]|3.46|<0.01|
|[[:human_genes:N:NOD1|NOD1]]|3.49|<0.01|
|[[:human_genes:H:HOXA7|HOXA7]]|3.50|<0.01|
|[[:human_genes:P:PLEKHA8|PLEKHA8]]|3.54|<0.01|
|[[:human_genes:E:ELMO1|ELMO1]]|3.56|<0.01|
|[[:human_genes:C:COL28A1|COL28A1]]|3.57|<0.01|
|[[:human_genes:G:GPR141|GPR141]]|3.59|<0.01|
|[[:human_genes:H:HIBADH|HIBADH]]|3.62|<0.01|
|[[:human_genes:D:DFNA5|DFNA5]]|3.63|<0.01|
|[[:human_genes:H:HOXA3|HOXA3]]|3.65|<0.01|
|[[:human_genes:C:CENPE|CENPE]]|3.68|<0.01|
|[[:human_genes:C:CYTH3|CYTH3]]|3.70|<0.01|
|[[:human_genes:Z:ZDHHC4|ZDHHC4]]|3.71|<0.01|
|[[:human_genes:T:TNRC18|TNRC18]]|3.73|<0.01|
|[[:human_genes:U:USP42|USP42]]|3.80|<0.01|
|[[:human_genes:P:PDE1C|PDE1C]]|3.82|<0.01|
|[[:human_genes:H:HOXA5|HOXA5]]|3.83|<0.01|
|[[:human_genes:C:C7orf41|C7orf41]]|4.11|<0.01|
|[[:human_genes:M:MAD2L1|MAD2L1]]|5.07|<0.01|
|[[:human_genes:Z:ZWILCH|ZWILCH]]|5.08|<0.01|
|[[:human_genes:R:RBM14-RBM4|RBM14-RBM4]]|5.72|<0.01|
|[[:human_genes:M:MAD2L1BP|MAD2L1BP]]|5.91|<0.01|
|[[:human_genes:M:MAD1L1|MAD1L1]]|6.31|<0.01|
|[[:human_genes:R:RBM14|RBM14]]|6.36|<0.01|
|[[:human_genes:C:CDC20|CDC20]]|6.44|<0.01|
|[[:human_genes:B:BUB1B|BUB1B]]|6.80|<0.01|
|[[:human_genes:B:BUB3|BUB3]]|6.90|<0.01|
|[[:human_genes:T:TRIP13|TRIP13]]|7.30|<0.01|
|[[:human_genes:Z:ZW10|ZW10]]|8.24|<0.01|
|[[:human_genes:K:KNTC1|KNTC1]]|8.27|<0.01|
^Screen^Correlation^Plot^
|[[:results:exp244|SB743921 0.001μM R05 exp244]]|0.338||
|[[:results:exp208|Vinblastine 0.015μM R05 exp208]]|0.225||
|[[:results:exp108|Vinblastine 0.2μM R03 exp108]]|0.052||
|[[:results:exp24|Nocodazole 0.2μM R00 exp24]]|0.387||
|[[:results:exp94|Nocodazole 0.1μM R03 exp94]]|0.343||
|[[:results:exp93|DABN racemic mixture R03 exp93]]|0.274||
|[[:results:exp111|R-DABN 8μM R03 exp111]]|0.256||
|[[:results:exp256|HMS-I1 10μM R06 exp256]]|0.211||
|[[:results:exp64|Nocodazole 0.2μM R02 exp64]]|0.197||
|[[:results:exp17|DABN 20μM R00 exp17]]|0.094||
|[[:results:exp98|BI-6727 0.04μM R03 exp98]]|0.092||
|[[:results:exp19|Etoposide 1μM R00 exp19]]|0.075||
|[[:results:exp34|Rotenone 20μM R00 exp34]]|0.069||
|[[:results:exp2|5-Fluorouracil 20μM R00 exp2]]|0.061||
|[[:results:exp28|Pimelic-diphenylamide-106 5μM R00 exp28]]|0.06||
|[[:results:exp3|Actinomycin-D 0.001μM R00 exp3]]|0.056||
{{:chemogenomics:comparison_plots:exp244_vs_exp33.png?nolink |}}
{{:chemogenomics:comparison_plots:exp208_vs_exp33.png?nolink |}}
{{:chemogenomics:comparison_plots:exp108_vs_exp33.png?nolink |}}
{{:chemogenomics:comparison_plots:exp24_vs_exp33.png?nolink |}}
{{:chemogenomics:comparison_plots:exp33_vs_exp94.png?nolink |}}
{{:chemogenomics:comparison_plots:exp33_vs_exp93.png?nolink |}}
{{:chemogenomics:comparison_plots:exp111_vs_exp33.png?nolink |}}
{{:chemogenomics:comparison_plots:exp256_vs_exp33.png?nolink |}}
{{:chemogenomics:comparison_plots:exp33_vs_exp64.png?nolink |}}
{{:chemogenomics:comparison_plots:exp17_vs_exp33.png?nolink |}}
{{:chemogenomics:comparison_plots:exp33_vs_exp98.png?nolink |}}
{{:chemogenomics:comparison_plots:exp19_vs_exp33.png?nolink |}}
{{:chemogenomics:comparison_plots:exp33_vs_exp34.png?nolink |}}
{{:chemogenomics:comparison_plots:exp2_vs_exp33.png?nolink |}}
{{:chemogenomics:comparison_plots:exp28_vs_exp33.png?nolink |}}
{{:chemogenomics:comparison_plots:exp3_vs_exp33.png?nolink |}}
^GO Term^Fold Change^Genes^
|Golgi lumen acidification|190.60|ATP6AP1,ATP6V0C,ATP6V1A|
|endosomal lumen acidification|131.95|ATP6AP1,ATP6V0C,ATP6V1A|
|synaptic vesicle lumen acidification|114.36|ATP6AP1,ATP6V1A,ATP6V1B2|
|proton-transporting V-type ATPase complex|84.71|ATP6AP1,ATP6V0C,ATP6V1A,ATP6V1B2|
|lysosomal lumen acidification|81.68|ATP6AP1,ATP6V0C,ATP6V1A|
|ATPase activity, coupled to transmembrane movement of ions, rotational mechanism|74.58|ATP6V0C,ATP6V1A,ATP6V1B2|
|proton-transporting ATPase activity, rotational mechanism|74.58|ATP6V0C,ATP6V1A,ATP6V1B2|
|ATPase-coupled ion transmembrane transporter activity|74.58|ATP6V0C,ATP6V1A,ATP6V1B2|
|vacuolar proton-transporting V-type ATPase complex|71.47|ATP6V0C,ATP6V1A,ATP6V1B2|
|regulation of lysosomal lumen pH|61.26|ATP6AP1,ATP6V0C,ATP6V1A|
|proton-transporting two-sector ATPase complex|50.83|ATP6AP1,ATP6V0C,ATP6V1A,ATP6V1B2|
|intracellular pH reduction|44.85|ATP6AP1,ATP6V0C,ATP6V1A,ATP6V1B2|
|regulation of intracellular pH|26.29|ATP6AP1,ATP6V0C,ATP6V1A,ATP6V1B2|
|regulation of cellular pH|24.86|ATP6AP1,ATP6V0C,ATP6V1A,ATP6V1B2|
|exocytic vesicle membrane|23.43|ATP6AP1,ATP6V0C,ATP6V1A,ATP6V1B2,SLC6A17|
|synaptic vesicle membrane|23.43|ATP6AP1,ATP6V0C,ATP6V1A,ATP6V1B2,SLC6A17|
|proton transmembrane transport|21.66|ATP6AP1,COX7A2L,ATP6V0C,ATP6V1A,ATP6V1B2|
|ATPase complex|20.42|ATP6AP1,ATP6V0C,ATP6V1A,ATP6V1B2,YY1|
|monoatomic cation transmembrane transport|7.22|ATP6AP1,COX7A2L,ATP6V0C,ATP6V1A,ATP6V1B2,MRS2,SLC6A12,SLC6A17|
^GO Term^Fold Change^Genes^
|mitotic spindle assembly checkpoint signaling|177.66|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,ZWILCH,MAD2L1|
|spindle assembly checkpoint signaling|177.66|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,ZWILCH,MAD2L1|
|mitotic spindle checkpoint signaling|177.66|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,ZWILCH,MAD2L1|
|negative regulation of mitotic sister chromatid separation|160.47|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,ZWILCH,MAD2L1|
|negative regulation of mitotic sister chromatid segregation|160.47|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,ZWILCH,MAD2L1|
|spindle checkpoint signaling|152.48|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,ZWILCH|
|negative regulation of chromosome separation|150.75|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,ZWILCH,MAD2L1|
|negative regulation of metaphase/anaphase transition of cell cycle|150.75|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,ZWILCH,MAD2L1|
|negative regulation of chromosome segregation|150.75|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,ZWILCH,MAD2L1|
|negative regulation of mitotic metaphase/anaphase transition|142.64|KNTC1,ZW10,TRIP13,BUB1B,CDC20,MAD1L1,ZWILCH,MAD2L1|
|negative regulation of sister chromatid segregation|142.64|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,ZWILCH|
|negative regulation of nuclear division|108.14|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,ZWILCH,MAD2L1|
|regulation of mitotic sister chromatid segregation|93.86|KNTC1,ZW10,TRIP13,BUB3,BUB1B,MAD1L1,MAD2L1BP,ZWILCH,MAD2L1|
|regulation of mitotic sister chromatid separation|85.77|ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,MAD2L1BP,ZWILCH,MAD2L1|
|regulation of chromosome separation|75.72|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,MAD2L1BP,ZWILCH,MAD2L1|
|regulation of mitotic metaphase/anaphase transition|68.32|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,MAD2L1BP,ZWILCH,MAD2L1,CENPE|
|regulation of metaphase/anaphase transition of cell cycle|66.09|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,MAD2L1BP,ZWILCH,MAD2L1,CENPE|
|regulation of sister chromatid segregation|59.03|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,MAD2L1BP,ZWILCH,MAD2L1,CENPE|
|regulation of chromosome segregation|48.25|KNTC1,ZW10,TRIP13,BUB3,BUB1B,CDC20,MAD1L1,MAD2L1BP,ZWILCH,MAD2L1,CENPE|