Rotenone 0.07μM R08 exp431

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

Compound References

PubChem Name: Rotenone
Synonyms: N/A
CAS #: 83-79-4
PubChem CID: 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

Compound Supplier

Supplier Name: Sigma-Aldrich
Catalog #: R8875
Lot #: SLBG7568V

Compound Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C23H22O6 395.14891; found 395.15075

Dose Response Curve

Platform ID: Rotenone
Min: 27.6098; Max: 94.6238

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

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	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
GOT1	-4.52	<0.01
SUCLG1	-3.28	<0.01
CHMP7	-2.93	<0.01
ADSS	-2.75	0.14
ACAT1	-2.74	0.02
MECR	-2.61	0.04
TMEM161B	-2.53	0.05
TSC1	-2.51	0.10
NUDT5	-2.50	0.10
HK1	-2.49	0.06
ESPL1	-2.33	0.35
GRPEL1	-2.32	0.47
MAN2C1	-2.31	0.12
AHCYL1	-2.29	0.17
SUCLA2	-2.29	0.12
CTR9	-2.26	0.17
EDF1	-2.24	0.17
PFKP	-2.23	0.15
SLC16A1	-2.19	0.35
GCDH	-2.19	0.16
DOPEY1	-2.19	0.16
ACACA	-2.18	0.22
CNOT2	-2.17	0.17
PGP	-2.16	0.23
LIPT1	-2.14	0.17
EXOG	-2.14	0.37
DEPTOR	-2.13	0.17
SEPHS2	-2.11	0.17
SWI5	-2.08	0.31
RIC8A	-2.06	0.22
RBM7	2.27	0.11
UGP2	2.28	0.06
PDHB	2.29	0.06
ACSL3	2.30	0.08
SKIV2L	2.31	0.10
ATP5D	2.36	0.07
BAK1	2.36	0.04
PMAIP1	2.41	0.04
CEPT1	2.44	0.03
KMT2D	2.48	0.03
PTDSS1	2.50	0.03
FDPS	2.51	0.04
ENY2	2.52	0.04
ASUN	2.54	0.02
GATC	2.54	0.02
G6PD	2.55	0.02
RHOBTB1	2.55	0.02
IKZF1	2.56	0.02
METTL14	2.57	0.10
SHMT2	2.64	0.05
PTPMT1	2.66	0.07
IPMK	2.72	0.01
MOCS3	2.78	0.03
AGPAT1	2.80	0.03
PGM3	3.01	<0.01
HSD17B12	3.05	0.02
FASTKD5	3.10	<0.01
ATP5A1	3.48	<0.01
ITPK1	3.70	<0.01
SLC25A51	4.34	<0.01

Screen	Correlation	Plot
iCRT14 30μM R08 exp492	0.071	View
TIC10 10μM R08 exp532	0.066	View
QNZ 0.01μM R08 exp439	0.212	View
Mubritinib 0.2μM R01 exp48	0.13	View
Mubritinib 0.2μM R02 exp65	0.114	View
QNZ 0.01μM R05 exp241	0.108	View
NMS-873 0.07μM R07 exp380	0.104	View
Phenformin 20μM R05 exp212	0.102	View
Amiloride 100μM R08 exp447	0.085	View
Chloramphenicol 20μM R00 exp13	0.076	View
∆-9-Tetrahydrocannabinol 30μM R08 exp445	0.065	View
Phenformin 20μM R03 exp143	0.057	View
CR131-b 0.005μM R08 exp474	0.057	View
Atovaquone 15μM R08 exp451	0.054	View
Nifuroxazide 5μM R03 exp102	0.054	View
MS023 7μM R03 exp135	0.054	View
Citral 75μM R06 exp275	0.053	View
Hippuristanol 0.12μM R08 exp488	0.052	View
Citral 50μM R06 exp274	0.051	View
AICAR 240μM R05 exp211	0.051	View

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

Rotenone 0.07μM R08 exp431

Mechanism of Action

Technical Notes

Compound References

Compound Supplier

Compound Characterization

Dose Response Curve

Screen Summary

Screen Results