Etoposide 0.3μM R05 exp199

Etoposide 0.3μM R05 exp199

Mechanism of Action

Binds DNA-TopII complex, blocks re-ligation, induces strand breaks, semi-synthetic derivative of podophyllotoxin

Class / Subclass 1: DNA Damage, Repair and Replication / Topoisomerase II Inhibitor

Technical Notes

Protein References

PubChem Name: Etoposide
Synonyms: VP-16; VP-16-213
CAS #: 33419-42-0
PubChem CID: 36462
IUPAC: (5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one
INCHI Name: InChI=1S/C29H32O13/c1-11-36-9-20-27(40-11)24(31)25(32)29(41-20)42-26-14-7-17-16(38-10-39-17)6-13(14)21(22-15(26)8-37-28(22)33)12-4-18(34-2)23(30)19(5-12)35-3/h4-7,11,15,20-22,24-27,29-32H,8-10H2,1-3H3/t11-,15+,20-,21-,22+,24-,25-,26-,27-,29+/m1/s1
INCHI Key: VJJPUSNTGOMMGY-MRVIYFEKSA-N
Molecular Weight: 588.6
Canonical SMILES: CC1OCC2C(O1)C(C(C(O2)OC3C4COC(=O)C4C(C5=CC6=C(C=C35)OCO6)C7=CC(=C(C(=C7)OC)O)OC)O)O
Isomeric SMILES: C[C@@H]1OC[C@@H]2[C@@H](O1)[C@@H]([C@H]([C@@H](O2)O[C@H]3[C@H]4COC(=O)[C@@H]4[C@@H](C5=CC6=C(C=C35)OCO6)C7=CC(=C(C(=C7)OC)O)OC)O)O
Molecular Formula: C29H32O13

Protein Supplier

Supplier Name: Sigma-Aldrich
Catalog #: E1383
Lot #: N/A

Protein Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C29H32O13 589.19157; found 589.19262

Dose Response Curve

Platform ID: Etoposide
Min: -33.3567; Max: 88.0314

IC	Concentration (µM)
IC10	N/A
IC20	0.1877
IC30	0.2644
IC40	0.3501
IC50	0.4531
IC60	N/A
IC70	N/A
IC80	N/A
IC90	N/A

Screen Summary

Round: 05
Dose: 300nM
Days of incubation: 8
Doublings: 0.4
Numbers of reads: 19028764

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
0/52	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
ZFAND5	-2.64	0.17
PSMA3	-2.63	0.22
MAP3K7	-2.60	0.22
CHMP2A	-2.56	0.38
UPF2	-2.55	0.24
ATP6V1D	-2.45	0.22
CEP192	-2.42	0.32
ATP6V0B	-2.42	0.24
SMG7	-2.42	0.24
HMG20B	-2.40	0.22
CHMP4B	-2.39	0.22
ZNF451	-2.36	0.22
INO80E	-2.30	0.24
MTCH2	-2.28	0.24
OSBP	-2.28	0.24
CNOT2	-2.26	0.22
PAN2	-2.24	0.22
CHMP6	-2.23	0.24
PSMC6	-2.17	0.59
MCM7	-2.16	0.38
POLR1A	-2.16	0.48
SUPT6H	-2.14	0.42
MR1	-2.12	0.24
PSMB4	-2.12	0.32
BRAP	-2.11	0.32
WDR53	-2.11	0.32
FAM72C	-2.11	0.68
CDT1	-2.10	0.61
FAM21A	-2.10	0.24
SRGAP2C	-2.09	0.68
ABCF1	2.68	0.01
BTF3	2.68	0.01
PHB	2.70	0.18
TP53	2.71	0.01
WDR24	2.74	<0.01
EIF4G1	2.78	<0.01
WDR59	2.83	<0.01
SERF2	2.86	<0.01
DIABLO	2.90	<0.01
ENY2	3.05	<0.01
CASP9	3.09	<0.01
RBM26	3.10	<0.01
PELO	3.10	<0.01
WDR82	3.14	<0.01
VHL	3.21	<0.01
HCCS	3.49	<0.01
EIF4A1	3.63	<0.01
MED16	3.66	<0.01
RPTOR	3.68	<0.01
CYCS	3.88	<0.01
MARCH5	3.88	<0.01
COPS7B	4.03	<0.01
FAF2	4.07	<0.01
NAA15	4.10	<0.01
UBQLN1	4.33	<0.01
VDAC2	4.83	<0.01
BAK1	5.42	<0.01
APAF1	5.85	<0.01
PLAA	6.92	<0.01
TOP2A	8.37	<0.01

Screen	Correlation	Plot
Etoposide 1μM R00 exp19	0.177	View
Mitomycin-C 0.06μM R08 exp503	0.127	View
Pimelic-diphenylamide-106 5μM R00 exp28	0.126	View
MS023 7μM R03 exp135	0.122	View
Rotenone 20μM R00 exp34	0.116	View
THZ1 0.06μM R08 exp531	0.103	View
RO-3307 4.7μM R02 exp80	0.099	View
SNS-032 15μM R08 exp443	0.092	View
PU-H71 1μM R08 exp515	0.089	View
Staurosporine 0.02μM R08 exp524	0.088	View
Tanespimycin 14μM R08 exp527	0.086	View
Pyridostatin 4μM R05 exp240	0.081	View
GSK626616 14μM R08 exp485	0.079	View
Olaparib 4μM R08 exp512	0.075	View
Hippuristanol 0.12μM R08 exp488	0.074	View
Hippuristanol 0.12μM R08 exp489 no dilution day6	0.072	View
MLN-4924 2μM R00 exp22	0.07	View
UM131593 0.2μM R03 exp106	0.068	View
UM0129480 7μM R02 exp85	0.068	View
GSK-J4 1.5μM R08 exp441	0.067	View
Vinblastine 0.2μM R03 exp108	0.065	View
Tozasertib 0.1μM R07 exp414	0.055	View
MLN-4924 0.2μM R00 exp21	0.055	View
Latrunculin-B 10μM R07 exp374	0.054	View
JQ1 0.8μM R08 exp435	0.052	View
GSK461364A 0.1μM R03 exp126	0.052	View
Oligomycin-A 20μM R00 exp26	0.052	View
MS023 2μM R03 exp134	0.051	View
Doxorubicin 0.02μM R08 exp478	0.198	View
5-Fluorouracil 20μM R00 exp2	0.164	View
Benzoate 20000μM R08 exp456	0.162	View
Bleomycin 5μM R08 exp459	0.15	View
Actinomycin-D 0.001μM R00 exp3	0.148	View
6-Thio-2-deoxyguanosine 2μM R06 exp259	0.109	View
Atovaquone 15μM R08 exp451	0.101	View
AICAR 240μM R05 exp211	0.101	View
CI-1040 9.5μM R08 exp472	0.096	View
Aphidicolin 0.4μM R08 exp440	0.085	View
Dinaciclib 0.007μM R07 exp355	0.077	View
Dorsomorphin 5μM R07 exp357	0.072	View
Deferoxamine 11μM R07 exp350	0.068	View
CR131-b 0.005μM R08 exp474	0.068	View
BI-2536 0.02μM R03 exp96	0.066	View
Ammonium tetrathiomolybdate 10μM R08 exp448	0.063	View
BI-6727 0.04μM R03 exp98	0.061	View
AICAR 240μM R03 exp116	0.061	View
Bortezomib 0.05μM R00 exp7	0.058	View
Artemisinin 50μM R08 exp450	0.056	View
42°C R08 exp539	0.055	View
CB-5083 0.4μM R08 exp468	0.055	View
DABN 20μM R00 exp17	0.054	View
Centrinone 0.5μM R07 exp343	0.052	View

GO Term	Fold Change	Genes
ESCRT III complex	204.57	CHMP2A,CHMP4B,CHMP6
vesicle fusion with vacuole	184.11	CHMP2A,CHMP4B,CHMP6
multivesicular body-lysosome fusion	184.11	CHMP2A,CHMP4B,CHMP6
vacuole fusion	167.37	CHMP2A,CHMP4B,CHMP6
amphisome	153.43	CHMP2A,CHMP4B,CHMP6
viral budding from plasma membrane	153.43	CHMP2A,CHMP4B,CHMP6
non-lytic viral release	141.62	CHMP2A,CHMP4B,CHMP6
midbody abscission	115.07	CHMP2A,CHMP4B,CHMP6
endosome to lysosome transport via multivesicular body sorting pathway	115.07	CHMP2A,CHMP4B,CHMP6
late endosome to lysosome transport	108.30	CHMP2A,CHMP4B,CHMP6
regulation of mitotic spindle assembly	87.67	CHMP2A,CHMP4B,CHMP6
mitotic metaphase chromosome alignment	48.13	CHMP2A,CHMP4B,CHMP6,CDT1
endosome organization	34.87	CHMP2A,ATP6V1D,ATP6V0B,CHMP4B,CHMP6
lytic vacuole organization	31.96	CHMP2A,ATP6V1D,ATP6V0B,CHMP4B,CHMP6
lysosome organization	31.96	CHMP2A,ATP6V1D,ATP6V0B,CHMP4B,CHMP6
mitotic sister chromatid segregation	22.56	CHMP2A,CEP192,CHMP4B,CHMP6,CDT1
sister chromatid segregation	21.92	CHMP2A,CEP192,CHMP4B,CHMP6,CDT1
endosome membrane	9.03	MAP3K7,CHMP2A,ATP6V1D,ATP6V0B,CHMP4B,CHMP6,MR1,WASHC2A
macromolecule catabolic process	6.67	PSMA3,CHMP2A,UPF2,SMG7,CHMP4B,CNOT2,PAN2,CHMP6,PSMC6,PSMB4

GO Term	Fold Change	Genes
apoptosome	552.33	APAF1,CASP9
activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c	441.87	APAF1,CYCS,CASP9,DIABLO
glial cell apoptotic process	276.17	CASP9,TP53
GATOR2 complex	276.17	WDR59,WDR24
positive regulation of mitochondrial membrane permeability	59.18	BAK1,VDAC2,TP53
positive regulation of membrane permeability	53.45	BAK1,VDAC2,TP53
negative regulation of autophagy	25.11	RPTOR,VHL,EIF4G1,TP53
positive regulation of cysteine-type endopeptidase activity	22.27	APAF1,BAK1,CYCS,CASP9,DIABLO
intrinsic apoptotic signaling pathway	20.71	APAF1,BAK1,CYCS,CASP9,DIABLO,TP53
positive regulation of endopeptidase activity	19.05	APAF1,BAK1,CYCS,CASP9,DIABLO
positive regulation of peptidase activity	17.37	APAF1,BAK1,CYCS,CASP9,DIABLO
response to endoplasmic reticulum stress	14.93	APAF1,BAK1,UBQLN1,FAF2,EIF4G1,TP53
regulation of cysteine-type endopeptidase activity	14.69	APAF1,BAK1,CYCS,CASP9,DIABLO
apoptotic signaling pathway	12.55	APAF1,BAK1,VDAC2,CYCS,CASP9,DIABLO,TP53
response to hypoxia	12.37	APAF1,UBQLN1,RPTOR,VHL,CASP9,TP53
response to decreased oxygen levels	11.63	APAF1,UBQLN1,RPTOR,VHL,CASP9,TP53
response to oxygen levels	10.66	APAF1,UBQLN1,RPTOR,VHL,CASP9,TP53
cellular response to external stimulus	10.20	BAK1,RPTOR,WDR59,EIF4G1,WDR24,TP53
positive regulation of proteolysis	9.83	APAF1,BAK1,UBQLN1,CYCS,CASP9,DIABLO

Table of Contents

Etoposide 0.3μM R05 exp199

Mechanism of Action

Technical Notes

Protein References

Protein Supplier

Protein Characterization

Dose Response Curve

Screen Summary

Screen Results