Etoposide 0.1μM R05 exp198

Etoposide 0.1μM R05 exp198

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

Compound 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

Compound Supplier

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

Compound 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: 100nM
Days of incubation: 8
Doublings: 2.5
Numbers of reads: 14351214

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
30/46	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
ABCC1	-4.25	<0.01
RAD54L2	-3.91	<0.01
TDP2	-3.80	<0.01
NHEJ1	-3.75	<0.01
FZR1	-3.52	<0.01
BRE	-3.38	<0.01
UBE2I	-3.37	<0.01
ZNF451	-3.19	<0.01
ZSWIM7	-3.09	<0.01
ATM	-3.01	<0.01
SWSAP1	-2.96	<0.01
DCLRE1C	-2.84	<0.01
SPIDR	-2.73	<0.01
CSNK2A1	-2.67	<0.01
SFR1	-2.66	<0.01
UBE2A	-2.63	0.01
RAD51D	-2.61	0.02
TP53BP1	-2.59	0.02
XRCC4	-2.59	0.01
SWI5	-2.55	0.03
GGPS1	-2.48	0.02
LIG4	-2.47	0.03
MAD2L2	-2.47	0.02
CCNB2	-2.46	0.02
NPRL2	-2.45	0.02
VPS25	-2.43	0.36
C18orf32	-2.42	0.36
RNF168	-2.42	0.03
QRICH1	-2.38	0.09
RBM14	-2.37	0.06
APAF1	2.66	<0.01
ZFC3H1	2.72	<0.01
WBP4	2.74	<0.01
RMI2	2.74	<0.01
ZBTB7A	2.79	<0.01
SF3B2	2.87	<0.01
EIF3G	2.96	<0.01
ERI1	2.96	<0.01
BRD1	3.01	<0.01
GPS1	3.03	<0.01
PKMYT1	3.03	<0.01
UBE2H	3.07	<0.01
UBE2K	3.13	<0.01
MEMO1	3.16	<0.01
VCP	3.26	<0.01
PLAA	3.30	<0.01
NAA15	3.31	<0.01
YWHAE	3.34	<0.01
MSL2	3.37	<0.01
ARID4B	3.55	<0.01
CKS2	3.61	<0.01
RAD23B	3.65	<0.01
CAND1	3.71	<0.01
PQBP1	3.78	<0.01
EIF4A1	4.03	<0.01
RBM26	4.29	<0.01
TOP2B	4.37	<0.01
WEE1	4.63	<0.01
COPS7B	5.57	<0.01
TOP2A	8.37	<0.01

Screen	Correlation	Plot
Pyridostatin 4μM R05 exp240	0.123	View
Genistein 15μM R07 exp360	0.111	View
Rucaparib 6.5μM R08 exp520	0.065	View
Olaparib 4μM R08 exp512	0.064	View
GSK626616 14μM R08 exp485	0.055	View
Doxorubicin 0.02μM R08 exp478	0.077	View

GO Term	Fold Change	Genes
DNA repair complex	177.54	NHEJ1,ATM,DCLRE1C,TP53BP1,XRCC4,LIG4
V(D)J recombination	174.05	NHEJ1,ATM,DCLRE1C,XRCC4,LIG4
double-strand break repair via nonhomologous end joining	98.63	NHEJ1,ATM,DCLRE1C,TP53BP1,XRCC4,LIG4,RNF168
somatic diversification of immune receptors via germline recombination within a single locus	86.60	NHEJ1,ATM,DCLRE1C,XRCC4,LIG4,RNF168
somatic cell DNA recombination	86.60	NHEJ1,ATM,DCLRE1C,XRCC4,LIG4,RNF168
somatic diversification of immune receptors	84.54	NHEJ1,ATM,DCLRE1C,XRCC4,LIG4,MAD2L2,RNF168
somatic diversification of immunoglobulins	79.97	NHEJ1,XRCC4,LIG4,MAD2L2,RNF168
immunoglobulin production	68.81	NHEJ1,XRCC4,LIG4,MAD2L2,RNF168
production of molecular mediator of immune response	62.96	NHEJ1,XRCC4,LIG4,MAD2L2,RNF168
cellular response to ionizing radiation	53.00	BABAM2,ATM,SPIDR,TP53BP1,SWI5,LIG4
double-strand break repair	47.11	TDP2,NHEJ1,BABAM2,ZSWIM7,ATM,SWSAP1,DCLRE1C,SPIDR,SFR1,RAD51D,TP53BP1,XRCC4,SWI5,LIG4,MAD2L2,RNF168
response to ionizing radiation	44.50	NHEJ1,BABAM2,ATM,DCLRE1C,SPIDR,TP53BP1,XRCC4,SWI5,LIG4,RNF168
recombinational repair	34.81	ZSWIM7,ATM,SWSAP1,SPIDR,SFR1,RAD51D,SWI5
DNA recombination	31.70	NHEJ1,ZSWIM7,ATM,SWSAP1,DCLRE1C,SPIDR,SFR1,RAD51D,XRCC4,SWI5,LIG4,RNF168
immune system development	29.41	NHEJ1,ATM,DCLRE1C,XRCC4,LIG4,MAD2L2,CCNB2,RNF168
DNA repair	22.62	TDP2,NHEJ1,FZR1,BABAM2,ZSWIM7,ATM,SWSAP1,DCLRE1C,SPIDR,SFR1,UBE2A,RAD51D,TP53BP1,XRCC4,SWI5,LIG4,MAD2L2,RNF168
response to radiation	15.88	NHEJ1,BABAM2,ATM,DCLRE1C,SPIDR,UBE2A,TP53BP1,XRCC4,SWI5,LIG4,RNF168
DNA damage response	14.90	TDP2,NHEJ1,FZR1,BABAM2,ZSWIM7,ATM,SWSAP1,DCLRE1C,SPIDR,SFR1,UBE2A,RAD51D,TP53BP1,XRCC4,SWI5,LIG4,MAD2L2,RNF168
DNA metabolic process	14.88	TDP2,NHEJ1,FZR1,BABAM2,ZSWIM7,ATM,SWSAP1,DCLRE1C,SPIDR,SFR1,UBE2A,RAD51D,TP53BP1,XRCC4,SWI5,LIG4,MAD2L2,RNF168

Table of Contents

Etoposide 0.1μM R05 exp198

Mechanism of Action

Technical Notes

Compound References

Compound Supplier

Compound Characterization

Dose Response Curve

Screen Summary

Screen Results