Actinomycin-D 0.001μM R00 exp3

Inhibits RNA polymerases, intercalates DNA, prevents chain elongation

Class / Subclass 1: Gene Regulation / Transcription Inhibitor

Compound References

PubChem Name: Dactinomycin
Synonyms: Dactinomycin; Actinomycin IV
CAS #: 50-76-0
PubChem CID: 457193
IUPAC: 2-amino-4,6-dimethyl-3-oxo-1-N,9-N-bis[(3R,6S,7R,10S,16S)-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-3,10-di(propan-2-yl)-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]phenoxazine-1,9-dicarboxamide
INCHI Name: InChI=1S/C62H86N12O16/c1-27(2)42-59(84)73-23-17-19-36(73)57(82)69(13)25-38(75)71(15)48(29(5)6)61(86)88-33(11)44(55(80)65-42)67-53(78)35-22-21-31(9)51-46(35)64-47-40(41(63)50(77)32(10)52(47)90-51)54(79)68-45-34(12)89-62(87)49(30(7)8)72(16)39(76)26-70(14)58(83)37-20-18-24-74(37)60(85)43(28(3)4)66-56(45)81/h21-22,27-30,33-34,36-37,42-45,48-49H,17-20,23-26,63H2,1-16H3,(H,65,80)(H,66,81)(H,67,78)(H,68,79)/t33-,34-,36+,37+,42-,43-,44+,45+,48+,49+/m1/s1
INCHI Key: RJURFGZVJUQBHK-IIXSONLDSA-N
Molecular Weight: 1255.4
Canonical SMILES: CC1C(C(=O)NC(C(=O)N2CCCC2C(=O)N(CC(=O)N(C(C(=O)O1)C(C)C)C)C)C(C)C)NC(=O)C3=C4C(=C(C=C3)C)OC5=C(C(=O)C(=C(C5=N4)C(=O)NC6C(OC(=O)C(N(C(=O)CN(C(=O)C7CCCN7C(=O)C(NC6=O)C(C)C)C)C)C(C)C)C)N)C
Isomeric SMILES: C[C@@H]1[C@@H](C(=O)N[C@@H](C(=O)N2CCC[C@H]2C(=O)N(CC(=O)N([C@H](C(=O)O1)C(C)C)C)C)C(C)C)NC(=O)C3=C4C(=C(C=C3)C)OC5=C(C(=O)C(=C(C5=N4)C(=O)N[C@H]6[C@H](OC(=O)[C@@H](N(C(=O)CN(C(=O)[C@@H]7CCCN7C(=O)[C@H](NC6=O)C(C)C)C)C)C(C)C)C)N)C
Molecular Formula: C62H86N12O16

Compound Supplier

Supplier Name: Sigma-Aldrich
Catalog #: A1410
Lot #: N/A

Compound Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C62H86N12O16 1255.63575; found 1255.63738

Dose Response Curve

Platform ID: Actinomycin_D
Min: -23.7457; Max: 97.9710

IC	Concentration (µM)
IC10	N/A
IC20	0.0002
IC30	0.0002
IC40	0.0002
IC50	0.0002
IC60	N/A
IC70	N/A
IC80	N/A
IC90	N/A

Screen Summary

Round: 00
Dose: 1nM
Days of incubation: 8
Doublings: 1.7
Numbers of reads: 9813688

Sensitive/Resistant hits (FDR<0.05)	CRANKS	Score Plot	Top 30 Genes	Screen Similarity	Top 30 Sensitive GO terms	Top 30 Resistant GO terms
15/132	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
MSI2	-3.40	<0.01
PSMC5	-3.21	0.05
WAPAL	-3.20	<0.01
SF3A1	-2.98	0.29
VPS51	-2.96	0.01
CNOT2	-2.95	<0.01
SIN3A	-2.85	0.02
HEXIM1	-2.85	0.01
BRD2	-2.69	0.02
TCF3	-2.65	0.03
ATP6AP2	-2.65	0.07
XPO1	-2.65	0.28
ABCB4	-2.65	0.03
LGI4	-2.64	0.02
TCF4	-2.59	0.03
ATXN2L	-2.58	0.04
EP300	-2.53	0.22
TSC2	-2.51	0.03
ING1	-2.46	0.04
GOLGA6L1	-2.42	0.37
GTPBP4	-2.38	0.16
PSMB3	-2.36	0.11
DHX8	-2.33	0.31
TCF12	-2.30	0.13
ZCCHC4	-2.29	0.17
ERCC3	-2.29	0.17
OSBP	-2.25	0.33
COX7A2L	-2.24	0.11
NUP133	-2.24	0.18
SLC22A14	-2.21	0.12
RB1	3.94	<0.01
RPL5	4.00	<0.01
FBXO11	4.04	<0.01
EIF4A1	4.08	<0.01
MCL1	4.09	<0.01
CDKN1A	4.20	<0.01
PPP6C	4.21	<0.01
SUV420H1	4.29	<0.01
RIOK3	4.40	<0.01
GTF3A	4.59	<0.01
MEAF6	4.69	<0.01
DIABLO	4.77	<0.01
UBE2K	4.79	<0.01
CYCS	4.80	<0.01
FAF2	4.95	<0.01
SPOP	5.00	<0.01
XPO7	5.15	<0.01
VDAC2	5.29	<0.01
NXT1	5.41	<0.01
HCCS	5.60	<0.01
CASP9	5.97	<0.01
PLAA	6.12	<0.01
APAF1	6.28	<0.01
ENY2	6.40	<0.01
HEATR3	6.60	<0.01
UBQLN1	6.90	<0.01
BAK1	7.03	<0.01
RPL11	7.54	<0.01
MARCH5	7.94	<0.01
TP53	8.50	<0.01

Screen	Correlation	Plot
Etoposide 1μM R00 exp19	0.165	View
Rotenone 20μM R00 exp34	0.158	View
Etoposide 0.3μM R05 exp199	0.148	View
Pimelic-diphenylamide-106 5μM R00 exp28	0.148	View
Benzoate 20000μM R08 exp456	0.127	View
Doxorubicin 0.02μM R08 exp478	0.124	View
Mitomycin-C 0.06μM R08 exp503	0.123	View
GSK626616 14μM R08 exp485	0.12	View
MLN-4924 2μM R00 exp22	0.119	View
Bleomycin 5μM R08 exp459	0.119	View
RO-3307 4.7μM R02 exp80	0.111	View
CI-1040 9.5μM R08 exp472	0.11	View
THZ1 0.06μM R08 exp531	0.106	View
UM131593 0.2μM R03 exp106	0.105	View
MS023 7μM R03 exp135	0.103	View
Staurosporine 0.02μM R08 exp524	0.096	View
Aphidicolin 0.4μM R08 exp440	0.091	View
Hippuristanol 0.12μM R08 exp489 no dilution day6	0.088	View
PU-H71 1μM R08 exp515	0.083	View
Hippuristanol 0.12μM R08 exp488	0.081	View
Olaparib 4μM R08 exp512	0.081	View
Tanespimycin 14μM R08 exp527	0.079	View
Dorsomorphin 5μM R07 exp357	0.078	View
Bortezomib 0.05μM R00 exp7	0.074	View
SNS-032 15μM R08 exp443	0.071	View
UM0129480 7μM R02 exp85	0.071	View
Atovaquone 15μM R08 exp451	0.07	View
JQ1 0.8μM R08 exp435	0.068	View
DABN 20μM R00 exp17	0.064	View
GSK461364A 0.1μM R03 exp126	0.064	View
Pyridostatin 4μM R05 exp240	0.062	View
Dinaciclib 0.007μM R07 exp355	0.062	View
MLN-4924 0.2μM R00 exp21	0.06	View
MS023 2μM R03 exp134	0.058	View
Diepoxybutane 3μM R07 exp354	0.058	View
Deferoxamine 11μM R07 exp350	0.058	View
CR131-b 0.005μM R08 exp474	0.056	View
Rotenone 2μM R00 exp33	0.056	View
BI-D1870 3.15μM R02 exp66	0.056	View
CB-5083 0.4μM R08 exp468	0.055	View
LY2090314 0.003μM R08 exp499	0.055	View
THZ531 0.225μM R08 exp444	0.055	View
Ammonium tetrathiomolybdate 10μM R08 exp448	0.053	View
GSK-J4 1.5μM R08 exp441	0.053	View
TRAIL 5ng/ml R00 exp35	0.052	View
UMK57 1μM R01 exp59	0.052	View
Milciclib 2μM R08 exp502	0.051	View
LY2090314 0.003μM R08 exp500 no dilution day6	0.051	View
5-Fluorouracil 20μM R00 exp2	0.31	View
AICAR 240μM R05 exp211	0.111	View
AICAR 240μM R03 exp116	0.087	View
6-Thio-2-deoxyguanosine 2μM R06 exp259	0.083	View
42°C R08 exp539	0.069	View

GO Term	Fold Change	Genes
apoptosome	552.73	APAF1,CASP9
activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c	442.19	APAF1,CASP9,CYCS,DIABLO
glial cell apoptotic process	414.55	TP53,CASP9,RB1
5S rRNA binding	207.28	RPL11,GTF3A,RPL5
release of cytochrome c from mitochondria	78.96	TP53,BAK1,MCL1
apoptotic mitochondrial changes	39.48	TP53,BAK1,VDAC2,MCL1
intrinsic apoptotic signaling pathway in response to DNA damage	38.92	TP53,BAK1,CASP9,CDKN1A,MCL1
intrinsic apoptotic signaling pathway	27.64	TP53,BAK1,APAF1,CASP9,CYCS,DIABLO,CDKN1A,MCL1
neuron apoptotic process	27.36	TP53,APAF1,CASP9,DIABLO,RB1
positive regulation of cysteine-type endopeptidase activity	22.29	BAK1,APAF1,CASP9,CYCS,DIABLO
positive regulation of endopeptidase activity	19.06	BAK1,APAF1,CASP9,CYCS,DIABLO
apoptotic signaling pathway	16.15	TP53,BAK1,APAF1,CASP9,VDAC2,CYCS,DIABLO,CDKN1A,MCL1
ubiquitin protein ligase binding	14.79	TP53,RPL11,SPOP,FAF2,UBE2K,CDKN1A,RPL5,RB1
nuclear transport	14.11	TP53,HEATR3,ENY2,NXT1,XPO7,CDKN1A
nucleocytoplasmic transport	14.11	TP53,HEATR3,ENY2,NXT1,XPO7,CDKN1A
ubiquitin-like protein ligase binding	13.95	TP53,RPL11,SPOP,FAF2,UBE2K,CDKN1A,RPL5,RB1
regulation of apoptotic signaling pathway	11.79	TP53,RPL11,BAK1,UBQLN1,APAF1,VDAC2,MCL1,RB1
regulation of proteolysis	10.31	TP53,RPL11,BAK1,UBQLN1,APAF1,CASP9,SPOP,CYCS,UBE2K,DIABLO,RPL5
positive regulation of programmed cell death	8.69	TP53,RPL11,BAK1,APAF1,CASP9,DIABLO,CDKN1A,MCL1

Actinomycin-D 0.001μM R00 exp3

Mechanism of Action

Technical Notes

Compound References

Compound Supplier

Compound Characterization

Dose Response Curve

Screen Summary

Screen Results