====== Rotenone 0.07μM R08 exp431 ====== ==== 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:** 27.6098; **Max:** 94.6238 {{:chemogenomics:dose_response:dr_577.png?nolink&500 |}} \\ \\ \\ \\ |< 300px 100px 200px >| ^ IC ^ Concentration (µM) ^ | IC10 |0.0001 | | IC20 |0.0013 | | IC30 |0.0061 | | IC40 |0.0217 | | IC50 |0.0692 | | IC60 |0.2208 | | IC70 |0.7819 | | IC80 |3.6570 | | IC90 |37.2500 | \\ ==== Screen Summary ==== * **Round**: 08 * **Dose**: 70nM * **Days of incubation**: 8 * **Doublings**: 2.9 * **Numbers of reads**: 16548653 ==== 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^ |5/22|[[https://files.tyerslab.com/files/public/chemogenomics/cranks/Rotenone_0.07uM_Round-8_exp431.txt|Scores]]|||||| {{:chemogenomics:cranks_plots:exp431.png?nolink}} ^Gene^CRANKS Score^FDR^ |[[:human_genes:G:GOT1|GOT1]]|-4.52|<0.01| |[[:human_genes:S:SUCLG1|SUCLG1]]|-3.28|<0.01| |[[:human_genes:C:CHMP7|CHMP7]]|-2.93|<0.01| |[[:human_genes:A:ADSS|ADSS]]|-2.75|0.14| |[[:human_genes:A:ACAT1|ACAT1]]|-2.74|0.02| |[[:human_genes:M:MECR|MECR]]|-2.61|0.04| |[[:human_genes:T:TMEM161B|TMEM161B]]|-2.53|0.05| |[[:human_genes:T:TSC1|TSC1]]|-2.51|0.10| |[[:human_genes:N:NUDT5|NUDT5]]|-2.50|0.10| |[[:human_genes:H:HK1|HK1]]|-2.49|0.06| |[[:human_genes:E:ESPL1|ESPL1]]|-2.33|0.35| |[[:human_genes:G:GRPEL1|GRPEL1]]|-2.32|0.47| |[[:human_genes:M:MAN2C1|MAN2C1]]|-2.31|0.12| |[[:human_genes:A:AHCYL1|AHCYL1]]|-2.29|0.17| |[[:human_genes:S:SUCLA2|SUCLA2]]|-2.29|0.12| |[[:human_genes:C:CTR9|CTR9]]|-2.26|0.17| |[[:human_genes:E:EDF1|EDF1]]|-2.24|0.17| |[[:human_genes:P:PFKP|PFKP]]|-2.23|0.15| |[[:human_genes:S:SLC16A1|SLC16A1]]|-2.19|0.35| |[[:human_genes:G:GCDH|GCDH]]|-2.19|0.16| |[[:human_genes:D:DOPEY1|DOPEY1]]|-2.19|0.16| |[[:human_genes:A:ACACA|ACACA]]|-2.18|0.22| |[[:human_genes:C:CNOT2|CNOT2]]|-2.17|0.17| |[[:human_genes:P:PGP|PGP]]|-2.16|0.23| |[[:human_genes:L:LIPT1|LIPT1]]|-2.14|0.17| |[[:human_genes:E:EXOG|EXOG]]|-2.14|0.37| |[[:human_genes:D:DEPTOR|DEPTOR]]|-2.13|0.17| |[[:human_genes:S:SEPHS2|SEPHS2]]|-2.11|0.17| |[[:human_genes:S:SWI5|SWI5]]|-2.08|0.31| |[[:human_genes:R:RIC8A|RIC8A]]|-2.06|0.22| |[[:human_genes:R:RBM7|RBM7]]|2.27|0.11| |[[:human_genes:U:UGP2|UGP2]]|2.28|0.06| |[[:human_genes:P:PDHB|PDHB]]|2.29|0.06| |[[:human_genes:A:ACSL3|ACSL3]]|2.30|0.08| |[[:human_genes:S:SKIV2L|SKIV2L]]|2.31|0.10| |[[:human_genes:A:ATP5D|ATP5D]]|2.36|0.07| |[[:human_genes:B:BAK1|BAK1]]|2.36|0.04| |[[:human_genes:P:PMAIP1|PMAIP1]]|2.41|0.04| |[[:human_genes:C:CEPT1|CEPT1]]|2.44|0.03| |[[:human_genes:K:KMT2D|KMT2D]]|2.48|0.03| |[[:human_genes:P:PTDSS1|PTDSS1]]|2.50|0.03| |[[:human_genes:F:FDPS|FDPS]]|2.51|0.04| |[[:human_genes:E:ENY2|ENY2]]|2.52|0.04| |[[:human_genes:A:ASUN|ASUN]]|2.54|0.02| |[[:human_genes:G:GATC|GATC]]|2.54|0.02| |[[:human_genes:G:G6PD|G6PD]]|2.55|0.02| |[[:human_genes:R:RHOBTB1|RHOBTB1]]|2.55|0.02| |[[:human_genes:I:IKZF1|IKZF1]]|2.56|0.02| |[[:human_genes:M:METTL14|METTL14]]|2.57|0.10| |[[:human_genes:S:SHMT2|SHMT2]]|2.64|0.05| |[[:human_genes:P:PTPMT1|PTPMT1]]|2.66|0.07| |[[:human_genes:I:IPMK|IPMK]]|2.72|0.01| |[[:human_genes:M:MOCS3|MOCS3]]|2.78|0.03| |[[:human_genes:A:AGPAT1|AGPAT1]]|2.80|0.03| |[[:human_genes:P:PGM3|PGM3]]|3.01|<0.01| |[[:human_genes:H:HSD17B12|HSD17B12]]|3.05|0.02| |[[:human_genes:F:FASTKD5|FASTKD5]]|3.10|<0.01| |[[:human_genes:A:ATP5A1|ATP5A1]]|3.48|<0.01| |[[:human_genes:I:ITPK1|ITPK1]]|3.70|<0.01| |[[:human_genes:S:SLC25A51|SLC25A51]]|4.34|<0.01| ^Screen^Correlation^Plot^ |[[:results:exp492|iCRT14 30μM R08 exp492]]|0.071|| |[[:results:exp532|TIC10 10μM R08 exp532]]|0.066|| |[[:results:exp439|QNZ 0.01μM R08 exp439]]|0.212|| |[[:results:exp48|Mubritinib 0.2μM R01 exp48]]|0.13|| |[[:results:exp65|Mubritinib 0.2μM R02 exp65]]|0.114|| |[[:results:exp241|QNZ 0.01μM R05 exp241]]|0.108|| |[[:results:exp380|NMS-873 0.07μM R07 exp380]]|0.104|| |[[:results:exp212|Phenformin 20μM R05 exp212]]|0.102|| |[[:results:exp447|Amiloride 100μM R08 exp447]]|0.085|| |[[:results:exp13|Chloramphenicol 20μM R00 exp13]]|0.076|| |[[:results:exp445|∆-9-Tetrahydrocannabinol 30μM R08 exp445]]|0.065|| |[[:results:exp143|Phenformin 20μM R03 exp143]]|0.057|| |[[:results:exp474|CR131-b 0.005μM R08 exp474]]|0.057|| |[[:results:exp451|Atovaquone 15μM R08 exp451]]|0.054|| |[[:results:exp102|Nifuroxazide 5μM R03 exp102]]|0.054|| |[[:results:exp135|MS023 7μM R03 exp135]]|0.054|| |[[:results:exp275|Citral 75μM R06 exp275]]|0.053|| |[[:results:exp488|Hippuristanol 0.12μM R08 exp488]]|0.052|| |[[:results:exp274|Citral 50μM R06 exp274]]|0.051|| |[[:results:exp211|AICAR 240μM R05 exp211]]|0.051|| {{:chemogenomics:comparison_plots:exp431_vs_exp492.png?nolink |}} {{:chemogenomics:comparison_plots:exp431_vs_exp532.png?nolink |}} {{:chemogenomics:comparison_plots:exp431_vs_exp439.png?nolink |}} {{:chemogenomics:comparison_plots:exp431_vs_exp48.png?nolink |}} {{:chemogenomics:comparison_plots:exp431_vs_exp65.png?nolink |}} {{:chemogenomics:comparison_plots:exp241_vs_exp431.png?nolink |}} {{:chemogenomics:comparison_plots:exp380_vs_exp431.png?nolink |}} {{:chemogenomics:comparison_plots:exp212_vs_exp431.png?nolink |}} {{:chemogenomics:comparison_plots:exp431_vs_exp447.png?nolink |}} {{:chemogenomics:comparison_plots:exp13_vs_exp431.png?nolink |}} {{:chemogenomics:comparison_plots:exp431_vs_exp445.png?nolink |}} {{:chemogenomics:comparison_plots:exp143_vs_exp431.png?nolink |}} {{:chemogenomics:comparison_plots:exp431_vs_exp474.png?nolink |}} {{:chemogenomics:comparison_plots:exp431_vs_exp451.png?nolink |}} {{:chemogenomics:comparison_plots:exp102_vs_exp431.png?nolink |}} {{:chemogenomics:comparison_plots:exp135_vs_exp431.png?nolink |}} {{:chemogenomics:comparison_plots:exp275_vs_exp431.png?nolink |}} {{:chemogenomics:comparison_plots:exp431_vs_exp488.png?nolink |}} {{:chemogenomics:comparison_plots:exp274_vs_exp431.png?nolink |}} {{:chemogenomics:comparison_plots:exp211_vs_exp431.png?nolink |}} ^GO Term^Fold Change^Genes^ |succinate-CoA ligase activity|571.34|SUCLG1,SUCLA2| |nucleoside bisphosphate catabolic process|155.82|SUCLG1,ACAT1,SUCLA2| |purine nucleoside bisphosphate catabolic process|155.82|SUCLG1,ACAT1,SUCLA2| |acyl-CoA metabolic process|32.84|SUCLG1,ACAT1,SUCLA2,GCDH,ACACA| |nucleoside bisphosphate metabolic process|24.84|SUCLG1,ACAT1,SUCLA2,GCDH,ACACA| |purine nucleoside bisphosphate metabolic process|24.84|SUCLG1,ACAT1,SUCLA2,GCDH,ACACA| |ribonucleoside bisphosphate metabolic process|24.84|SUCLG1,ACAT1,SUCLA2,GCDH,ACACA| |purine ribonucleotide metabolic process|12.58|SUCLG1,ADSS2,ACAT1,NUDT5,SUCLA2,GCDH,ACACA| |nucleobase-containing compound catabolic process|12.16|SUCLG1,ACAT1,NUDT5,SUCLA2,CNOT2,EXOG| |ribonucleotide metabolic process|11.87|SUCLG1,ADSS2,ACAT1,NUDT5,SUCLA2,GCDH,ACACA| |sulfur compound metabolic process|11.70|SUCLG1,ACAT1,AHCYL1,SUCLA2,GCDH,ACACA| |ribose phosphate metabolic process|11.59|SUCLG1,ADSS2,ACAT1,NUDT5,SUCLA2,GCDH,ACACA| |small molecule catabolic process|11.39|GOT1,ACAT1,NUDT5,HK1,PFKP,SLC16A1,GCDH| |purine nucleotide metabolic process|10.07|SUCLG1,ADSS2,ACAT1,NUDT5,SUCLA2,GCDH,ACACA| |purine-containing compound metabolic process|9.41|SUCLG1,ADSS2,ACAT1,NUDT5,SUCLA2,GCDH,ACACA| |carboxylic acid metabolic process|8.52|GOT1,ADSS2,ACAT1,MECR,HK1,SUCLA2,PFKP,SLC16A1,GCDH,ACACA,LIPT1,SEPHS2| |oxoacid metabolic process|8.29|GOT1,ADSS2,ACAT1,MECR,HK1,SUCLA2,PFKP,SLC16A1,GCDH,ACACA,LIPT1,SEPHS2| |organic acid metabolic process|8.22|GOT1,ADSS2,ACAT1,MECR,HK1,SUCLA2,PFKP,SLC16A1,GCDH,ACACA,LIPT1,SEPHS2| |organophosphate metabolic process|6.64|SUCLG1,ADSS2,ACAT1,NUDT5,HK1,SUCLA2,PFKP,GCDH,ACACA,PGP| ^GO Term^Fold Change^Genes^ |inositol trisphosphate kinase activity|276.15|ITPK1,IPMK| |inositol tetrakisphosphate kinase activity|276.15|ITPK1,IPMK| |thioester biosynthetic process|41.42|HSD17B12,ACSL3,PDHB| |ligase activity|21.11|ATP5F1A,MOCS3,GATC,ATP5F1D,ACSL3,LARS2| |ribose phosphate biosynthetic process|17.08|ATP5F1A,HSD17B12,G6PD,ATP5F1D,ACSL3,PDHB| |purine ribonucleotide biosynthetic process|15.96|ATP5F1A,HSD17B12,ATP5F1D,ACSL3,PDHB| |purine-containing compound biosynthetic process|15.13|ATP5F1A,HSD17B12,SHMT2,ATP5F1D,ACSL3,PDHB| |ribonucleotide biosynthetic process|14.77|ATP5F1A,HSD17B12,ATP5F1D,ACSL3,PDHB| |organophosphate biosynthetic process|13.91|ATP5F1A,HSD17B12,AGPAT1,MOCS3,IPMK,PTPMT1,G6PD,FDPS,PTDSS1,CEPT1,ATP5F1D,ACSL3,PDHB| |purine nucleotide biosynthetic process|13.15|ATP5F1A,HSD17B12,ATP5F1D,ACSL3,PDHB| |organophosphate metabolic process|9.62|ITPK1,ATP5F1A,HSD17B12,AGPAT1,MOCS3,IPMK,PTPMT1,G6PD,FDPS,PTDSS1,CEPT1,ATP5F1D,ACSL3,PDHB,UGP2| |ribose phosphate metabolic process|9.61|ATP5F1A,HSD17B12,G6PD,ATP5F1D,ACSL3,PDHB| |phospholipid metabolic process|9.58|AGPAT1,IPMK,PTPMT1,FDPS,PTDSS1,CEPT1| |nucleobase-containing small molecule metabolic process|9.33|ATP5F1A,HSD17B12,PGM3,SHMT2,G6PD,ATP5F1D,ACSL3,PDHB,UGP2| |purine-containing compound metabolic process|9.10|ATP5F1A,HSD17B12,SHMT2,G6PD,ATP5F1D,ACSL3,PDHB| |generation of precursor metabolites and energy|8.84|SLC25A51,ATP5F1A,G6PD,ATP5F1D,PDHB,UGP2| |mitochondrial membrane|6.27|SLC25A51,ATP5F1A,PTPMT1,SHMT2,PMAIP1,BAK1,ATP5F1D,ACSL3| |mitochondrial envelope|5.88|SLC25A51,ATP5F1A,PTPMT1,SHMT2,PMAIP1,BAK1,ATP5F1D,ACSL3| |heterocycle biosynthetic process|5.52|ATP5F1A,HSD17B12,PGM3,MOCS3,SHMT2,ENY2,ATP5F1D,ACSL3,PDHB|