Mitomycin-C 0.06μM R08 exp503

DNA crosslinker, reductive activation forms a mitosene that N-alkylates successively DNA bases

Class / Subclass 1: DNA Damage, Repair and Replication / Inter/Intra-strand Crosslinker

Compound References

PubChem Name: Mitomycin
Synonyms: Ametycine
CAS #: 50-07-7
PubChem CID: 5746
IUPAC: [(4S,6S,7R,8S)-11-amino-7-methoxy-12-methyl-10,13-dioxo-2,5-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),11-dien-8-yl]methyl carbamate
INCHI Name: InChI=1S/C15H18N4O5/c1-5-9(16)12(21)8-6(4-24-14(17)22)15(23-2)13-7(18-13)3-19(15)10(8)11(5)20/h6-7,13,18H,3-4,16H2,1-2H3,(H2,17,22)/t6-,7+,13+,15-/m1/s1
INCHI Key: NWIBSHFKIJFRCO-WUDYKRTCSA-N
Molecular Weight: 334.33
Canonical SMILES: CC1=C(C(=O)C2=C(C1=O)N3CC4C(C3(C2COC(=O)N)OC)N4)N
Isomeric SMILES: CC1=C(C(=O)C2=C(C1=O)N3C[C@H]4[C@@H]([C@@]3([C@@H]2COC(=O)N)OC)N4)N
Molecular Formula: C15H18N4O5

Compound Supplier

Supplier Name: Toronto Research Chemicals
Catalog #: M371900
Lot #: 1-AWT-3-1

Compound Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C15H18N4O5 335.135; found 335.13842

Dose Response Curve

Platform ID: MMC
Min: -9.1662; Max: 98.4658

IC	Concentration (µM)
IC10	0.0334
IC20	0.0482
IC30	0.0615
IC40	0.0751
IC50	0.0902
IC60	0.1083
IC70	0.1322
IC80	0.1687
IC90	0.2433

Screen Summary

Round: 08
Dose: 60nM
Days of incubation: 8
Doublings: 1.3
Numbers of reads: 16051073

Sensitive/Resistant hits (FDR<0.05)	CRANKS	Score Plot	Top 30 Genes	Screen Similarity	Top 30 Sensitive GO terms	Top 30 Resistant GO terms
0/56	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
HMGCR	-2.93	0.38
LARS	-2.65	0.62
MDM2	-2.65	0.34
GPX4	-2.44	0.34
TRIM16	-2.43	0.35
SLC17A5	-2.41	0.34
EXOSC4	-2.38	0.49
BRD2	-2.34	0.38
CDK8	-2.29	0.43
POLR2L	-2.26	0.64
RPS11	-2.26	0.62
DDX47	-2.22	0.62
VPS25	-2.21	0.62
NFS1	-2.18	0.63
NAT10	-2.17	0.62
CHAF1A	-2.15	0.62
POLR2J	-2.13	0.63
APOA4	-2.12	0.62
HENMT1	-2.09	0.49
PSMA7	-2.09	0.62
ARCN1	-2.07	0.62
OTUB1	-2.02	0.62
ATG4D	-2.01	0.62
MAU2	-1.99	0.63
MAP3K7	-1.98	0.62
TBCC	-1.97	0.66
REV1	-1.96	0.62
RPS17L	-1.96	0.63
ESPL1	-1.96	0.62
MGA	-1.96	0.62
THG1L	2.79	<0.01
TRMT61A	2.80	0.01
NSD1	2.88	<0.01
ATP5O	2.93	<0.01
UBE2K	2.95	<0.01
ROMO1	3.01	<0.01
UHRF1	3.03	<0.01
MARCH5	3.10	<0.01
PCBP2	3.11	0.00
MRPS33	3.12	<0.01
BAP1	3.13	0.00
CEPT1	3.14	0.00
FBXO11	3.24	0.00
PML	3.41	0.00
FAF2	3.46	0.00
DOHH	3.51	0.00
VDAC2	3.61	0.00
UBQLN1	3.78	0.00
PLAA	3.94	0.00
ENY2	3.95	0.00
SLC52A2	4.39	0.00
RMI1	4.44	0.00
CASP9	4.57	0.00
RMI2	4.76	0.00
APAF1	5.39	0.00
RFK	6.24	0.00
SLFN11	6.41	0.00
TP53	6.49	0.00
DUS1L	6.53	0.00
BAK1	6.56	0.00

Screen	Correlation	Plot
Olaparib 4μM R08 exp512	0.121	View
THZ1 0.06μM R08 exp531	0.12	View
PU-H71 1μM R08 exp515	0.118	View
SNS-032 15μM R08 exp443	0.117	View
Pimelic-diphenylamide-106 5μM R00 exp28	0.116	View
Staurosporine 0.02μM R08 exp524	0.116	View
Tanespimycin 14μM R08 exp527	0.112	View
TIC10 10μM R08 exp532	0.11	View
Rotenone 20μM R00 exp34	0.107	View
RO-3307 4.7μM R02 exp80	0.105	View
UM131593 0.2μM R03 exp106	0.09	View
Thimerosal 0.85μM R08 exp529	0.071	View
UM0129480 7μM R02 exp85	0.064	View
ONC212 0.15μM R08 exp513	0.063	View
Nutlin-3A 1.6μM R06 exp294	0.063	View
QNZ 0.01μM R08 exp439	0.054	View
Quercetin 20μM R08 exp517	0.051	View
Benzoate 20000μM R08 exp456	0.156	View
Bleomycin 5μM R08 exp459	0.15	View
Aphidicolin 0.4μM R08 exp440	0.14	View
5-Fluorouracil 20μM R00 exp2	0.139	View
Atovaquone 15μM R08 exp451	0.135	View
Doxorubicin 0.02μM R08 exp478	0.127	View
Etoposide 0.3μM R05 exp199	0.127	View
CI-1040 9.5μM R08 exp472	0.125	View
Actinomycin-D 0.001μM R00 exp3	0.123	View
Hippuristanol 0.12μM R08 exp488	0.106	View
AICAR 240μM R05 exp211	0.098	View
JQ1 0.8μM R08 exp435	0.096	View
GSK-J4 1.5μM R08 exp441	0.096	View
Etoposide 1μM R00 exp19	0.095	View
MS023 7μM R03 exp135	0.095	View
Hippuristanol 0.12μM R08 exp489 no dilution day6	0.092	View
GSK626616 14μM R08 exp485	0.087	View
6-Thio-2-deoxyguanosine 2μM R06 exp259	0.086	View
Dorsomorphin 5μM R07 exp357	0.083	View
Artemisinin 50μM R08 exp450	0.078	View
BI-2536 0.02μM R03 exp96	0.078	View
CR131-b 0.005μM R08 exp474	0.078	View
Diepoxybutane 3μM R07 exp354	0.072	View
Dinaciclib 0.007μM R07 exp355	0.072	View
AICAR 240μM R03 exp116	0.069	View
BI-6727 0.04μM R03 exp98	0.067	View
Deferoxamine 11μM R07 exp350	0.064	View
Ammonium tetrathiomolybdate 10μM R08 exp448	0.063	View
MLN-4924 2μM R00 exp22	0.061	View
42°C R08 exp539	0.06	View
MS023 2μM R03 exp134	0.06	View
Centrinone 0.5μM R07 exp343	0.058	View
GSK461364A 0.1μM R03 exp126	0.057	View
DABN racemic mixture R03 exp93	0.057	View
Milciclib 2μM R08 exp502	0.055	View
Latrunculin-B 10μM R07 exp374	0.054	View
Hydroxyurea 100μM R07 exp329	0.051	View

GO Term	Fold Change	Genes
apoptosome	552.30	APAF1,CASP9
RecQ family helicase-topoisomerase III complex	368.20	RMI2,RMI1
glial cell apoptotic process	276.15	TP53,CASP9
flavin-containing compound metabolic process	220.92	RFK,SLC52A2
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	66.95	BAK1,TP53,APAF1,PML
positive regulation of mitochondrial membrane permeability	59.18	BAK1,TP53,VDAC2
positive regulation of membrane permeability	53.45	BAK1,TP53,VDAC2
intrinsic apoptotic signaling pathway in response to DNA damage	31.12	BAK1,TP53,CASP9,PML
intrinsic apoptotic signaling pathway	17.26	BAK1,TP53,APAF1,CASP9,PML
response to endoplasmic reticulum stress	14.73	BAK1,TP53,APAF1,UBQLN1,FAF2,PML
apoptotic signaling pathway	10.76	BAK1,TP53,APAF1,CASP9,VDAC2,PML
ubiquitin-dependent protein catabolic process	9.73	PLAA,UBQLN1,FAF2,PML,FBXO11,BAP1,PCBP2,UHRF1,UBE2K
proteasome-mediated ubiquitin-dependent protein catabolic process	9.61	PLAA,UBQLN1,FAF2,PML,PCBP2,UBE2K
modification-dependent protein catabolic process	9.54	PLAA,UBQLN1,FAF2,PML,FBXO11,BAP1,PCBP2,UHRF1,UBE2K
modification-dependent macromolecule catabolic process	9.34	PLAA,UBQLN1,FAF2,PML,FBXO11,BAP1,PCBP2,UHRF1,UBE2K
proteolysis involved in protein catabolic process	8.53	PLAA,UBQLN1,FAF2,PML,FBXO11,BAP1,PCBP2,UHRF1,UBE2K
protein catabolic process	7.15	PLAA,UBQLN1,FAF2,PML,FBXO11,BAP1,PCBP2,UHRF1,UBE2K
DNA damage response	6.21	BAK1,TP53,SLFN11,RMI2,CASP9,RMI1,PML,UHRF1
macromolecule catabolic process	5.39	PLAA,UBQLN1,FAF2,PML,FBXO11,BAP1,PCBP2,UHRF1,UBE2K

Mitomycin-C 0.06μM R08 exp503

Mechanism of Action

Technical Notes

Compound References

Compound Supplier

Compound Characterization

Dose Response Curve

Screen Summary

Screen Results