Olaparib 4μM R08 exp512

Inhibits PARP1 and PARP2, blocks ssDNA break repair, selectively toxic to BRCA1/2 negative cancers

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

Compound References

PubChem Name: Olaparib
Synonyms: AZD2281; KU0059436
CAS #: 763113-22-0
PubChem CID: 23725625
IUPAC: 4-[[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one
INCHI Name: InChI=1S/C24H23FN4O3/c25-20-8-5-15(14-21-17-3-1-2-4-18(17)22(30)27-26-21)13-19(20)24(32)29-11-9-28(10-12-29)23(31)16-6-7-16/h1-5,8,13,16H,6-7,9-12,14H2,(H,27,30)
INCHI Key: FDLYAMZZIXQODN-UHFFFAOYSA-N
Molecular Weight: 434.5
Canonical SMILES: C1CC1C(=O)N2CCN(CC2)C(=O)C3=C(C=CC(=C3)CC4=NNC(=O)C5=CC=CC=C54)F
Isomeric SMILES: N/A
Molecular Formula: C24H23FN4O3

Compound Supplier

Supplier Name: Med Chem Express
Catalog #: HY-10162
Lot #: 24830

Compound Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C24H23FN4O3 435.1827; found 435.18457

Dose Response Curve

Platform ID: Olaparib
Min: -6.7026; Max: 94.1282

IC	Concentration (µM)
IC10	2.5010
IC20	3.3100
IC30	3.9880
IC40	4.6460
IC50	5.3450
IC60	6.1490
IC70	7.1640
IC80	8.6310
IC90	11.4200

Screen Summary

Round: 08
Dose: 4µM
Days of incubation: 8
Doublings: 2.2
Numbers of reads: 17298761

Sensitive/Resistant hits (FDR<0.05)	CRANKS	Score Plot	Top 30 Genes	Screen Similarity	Top 30 Sensitive GO terms	Top 30 Resistant GO terms
42/114	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
MCM9	-4.83	0.00
PRDX1	-4.38	0.00
DNPH1	-3.97	0.00
SWSAP1	-3.85	0.00
SMARCAL1	-3.83	0.00
APITD1	-3.70	0.00
GTPBP2	-3.65	0.00
POLB	-3.55	0.00
APITD1-CORT	-3.48	0.00
UBE2N	-3.30	0.00
ZBTB1	-3.28	0.00
RAD54L	-3.24	0.00
HELLS	-3.22	0.00
ZSWIM7	-3.16	0.00
KPNA3	-3.13	<0.01
SIVA1	-3.03	<0.01
MDM2	-3.03	<0.01
YPEL5	-2.99	<0.01
HELQ	-2.98	<0.01
VPS25	-2.82	0.13
NFRKB	-2.73	<0.01
KPNA4	-2.68	<0.01
C1orf112	-2.67	<0.01
RNF168	-2.67	<0.01
SPIDR	-2.67	<0.01
LIG3	-2.66	0.01
ITPA	-2.54	0.01
USP7	-2.54	0.02
STRA13	-2.50	0.01
RNASEH2A	-2.49	0.05
CASP9	3.35	0.00
CYCS	3.36	0.00
PLAA	3.41	0.00
ALAS1	3.42	<0.01
TFDP1	3.48	0.00
FAF2	3.48	0.00
GCN1L1	3.48	0.00
SLC20A1	3.50	0.00
RPS25	3.55	0.00
ENY2	3.56	0.00
EIF4A1	3.57	0.00
TRMT10A	3.62	0.00
NSUN2	3.65	0.00
ZCCHC8	3.71	0.00
VDAC2	3.82	0.00
DIABLO	3.88	0.00
RICTOR	3.98	0.00
MLST8	4.02	0.00
PMAIP1	4.26	0.00
IRF2	4.28	0.00
PARP2	4.53	0.00
MAPKAP1	4.53	0.00
AHCYL1	4.60	0.00
APAF1	4.97	0.00
MARCH5	5.41	0.00
ADPRHL2	5.99	0.00
BAK1	6.55	0.00
SLFN11	6.79	0.00
TP53	7.12	0.00
PARP1	7.76	0.00

Screen	Correlation	Plot
Rucaparib 6.5μM R08 exp520	0.204	View
Talazoparib 0.006μM R06 exp299	0.088	View
Thimerosal 0.85μM R08 exp529	0.086	View
SNS-032 15μM R08 exp443	0.083	View
Trimetrexate 0.03μM R08 exp535	0.082	View
Sulforaphane 9μM R08 exp525	0.079	View
RO-3307 4.7μM R02 exp80	0.077	View
Pterostilbene 16μM R02 exp78	0.075	View
THZ1 0.06μM R08 exp531	0.074	View
Staurosporine 0.02μM R08 exp524	0.072	View
Pimelic-diphenylamide-106 5μM R00 exp28	0.069	View
Quercetin 20μM R08 exp517	0.067	View
Sulforaphane 9μM R08 exp526 no dilution day6	0.064	View
UM0129480 7μM R02 exp85	0.063	View
PU-H71 1μM R08 exp515	0.059	View
TRAIL 50ng/ml R00 exp36	0.058	View
Pyridostatin 4μM R05 exp240	0.057	View
Resveratrol 16μM R03 exp147	0.055	View
Rotenone 20μM R00 exp34	0.055	View
Aphidicolin 0.4μM R08 exp440	0.16	View
Mitomycin-C 0.06μM R08 exp503	0.121	View
Hippuristanol 0.12μM R08 exp489 no dilution day6	0.117	View
Diepoxybutane 3μM R07 exp354	0.116	View
Hippuristanol 0.12μM R08 exp488	0.115	View
Benzoate 20000μM R08 exp456	0.113	View
MS023 7μM R03 exp135	0.105	View
AICAR 240μM R05 exp211	0.104	View
Ethanol 0.01 R05 exp234	0.093	View
GSK626616 14μM R08 exp485	0.092	View
AICAR 240μM R03 exp116	0.091	View
Bleomycin 5μM R08 exp459	0.09	View
MS023 2μM R03 exp134	0.09	View
5-Fluorouracil 20μM R00 exp2	0.086	View
Actinomycin-D 0.001μM R00 exp3	0.081	View
Nutlin-3A 1.6μM R06 exp294	0.078	View
Doxorubicin 0.02μM R08 exp478	0.076	View
CR131-b 0.005μM R08 exp474	0.076	View
Dinaciclib 0.007μM R07 exp355	0.076	View
Etoposide 0.3μM R05 exp199	0.075	View
6-Thio-2-deoxyguanosine 2μM R06 exp259	0.073	View
Hydroxyurea 100μM R07 exp329	0.073	View
Latrunculin-B 10μM R07 exp374	0.072	View
CI-1040 9.5μM R08 exp472	0.07	View
JQ1 0.8μM R08 exp435	0.07	View
Dorsomorphin 5μM R07 exp357	0.069	View
Cytochalasin-B 5μM R07 exp349	0.066	View
Artemisinin 50μM R08 exp450	0.066	View
2-Deoxy-D-glucose 800μM R05 exp214	0.065	View
Etoposide 0.1μM R05 exp198	0.064	View
MLN-4924 0.2μM R00 exp21	0.062	View
ML-792 0.2μM R08 exp505	0.061	View
CB-5083 0.4μM R08 exp468	0.06	View
Bortezomib 0.005μM R00 exp6	0.06	View
Aminopterin 0.005μM R07 exp335	0.057	View
Etoposide 1μM R00 exp19	0.057	View
Campthothecin 0.001μM R06 exp270	0.056	View
3-Bromopyruvate 7μM R04 exp175	0.056	View
MK-1775 0.32μM R02 exp75	0.055	View
Lead acetate 2000μM R08 exp497	0.055	View
Lead acetate 2000μM R08 exp498 no dilution day6	0.054	View
GSK-J4 1.5μM R08 exp441	0.052	View

GO Term	Fold Change	Genes
interstrand cross-link repair	72.20	MCM9,CENPS,RNF168,CENPX
double-strand break repair via nonhomologous end joining	58.44	SMARCAL1,POLB,HELQ,RNF168
DNA-templated DNA replication maintenance of fidelity	46.31	MCM9,SMARCAL1,CENPS,CENPX
recombinational repair	41.25	MCM9,SWSAP1,UBE2N,RAD54L,ZSWIM7,HELQ,SPIDR,LIG3
double-strand break repair via homologous recombination	37.03	MCM9,UBE2N,RAD54L,ZSWIM7,HELQ,SPIDR,LIG3
DNA recombination	35.77	MCM9,SWSAP1,CENPS,POLB,UBE2N,RAD54L,ZSWIM7,HELQ,NFRKB,RNF168,SPIDR,LIG3,CENPX
double-strand break repair	33.58	MCM9,SWSAP1,SMARCAL1,POLB,UBE2N,RAD54L,ZSWIM7,HELQ,RNF168,SPIDR,LIG3
DNA-templated DNA replication	28.32	MCM9,SMARCAL1,CENPS,POLB,LIG3,CENPX
ATP-dependent activity, acting on DNA	26.92	MCM9,SMARCAL1,RAD54L,HELLS,HELQ
positive regulation of DNA repair	25.36	UBE2N,HELQ,NFRKB,RNF168,SPIDR
response to ionizing radiation	23.24	POLB,RAD54L,MDM2,RNF168,SPIDR
DNA repair	20.94	MCM9,SWSAP1,SMARCAL1,CENPS,POLB,UBE2N,ZBTB1,RAD54L,ZSWIM7,HELQ,NFRKB,RNF168,SPIDR,LIG3,USP7,CENPX
helicase activity	20.59	MCM9,SMARCAL1,RAD54L,HELLS,HELQ
DNA replication	19.08	MCM9,SMARCAL1,CENPS,POLB,LIG3,CENPX
catalytic activity, acting on DNA	18.28	MCM9,SMARCAL1,POLB,RAD54L,HELLS,HELQ,LIG3
DNA damage response	14.65	MCM9,SWSAP1,SMARCAL1,CENPS,POLB,UBE2N,ZBTB1,RAD54L,ZSWIM7,MDM2,HELQ,NFRKB,RNF168,SPIDR,LIG3,USP7,CENPX
DNA metabolic process	14.61	MCM9,SWSAP1,SMARCAL1,CENPS,POLB,UBE2N,ZBTB1,RAD54L,HELLS,ZSWIM7,HELQ,NFRKB,RNF168,SPIDR,LIG3,USP7,CENPX
positive regulation of DNA metabolic process	12.92	UBE2N,HELQ,NFRKB,RNF168,SPIDR,USP7
chromosome organization	9.76	MCM9,SMARCAL1,RAD54L,HELQ,NFRKB,ITPA,CENPX

GO Term	Fold Change	Genes
apoptosome	552.30	APAF1,CASP9
NAD DNA ADP-ribosyltransferase activity	552.30	PARP1,PARP2
activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c	441.84	APAF1,DIABLO,CYCS,CASP9
TORC2 complex	207.11	MAPKAP1,MLST8,RICTOR
regulation of mitochondrial membrane permeability	40.17	TP53,BAK1,PMAIP1,VDAC2
apoptotic mitochondrial changes	39.45	TP53,BAK1,PMAIP1,VDAC2
neuron apoptotic process	27.34	TP53,APAF1,PARP2,DIABLO,CASP9
positive regulation of cysteine-type endopeptidase activity	26.94	BAK1,APAF1,PMAIP1,DIABLO,CYCS,CASP9
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	26.30	APAF1,PMAIP1,DIABLO,CYCS,CASP9
site of DNA damage	25.57	PARP1,TP53,SLFN11,ADPRS,PARP2
intrinsic apoptotic signaling pathway	24.16	TP53,BAK1,APAF1,PMAIP1,DIABLO,CYCS,CASP9
positive regulation of endopeptidase activity	23.01	BAK1,APAF1,PMAIP1,DIABLO,CYCS,CASP9
positive regulation of peptidase activity	20.97	BAK1,APAF1,PMAIP1,DIABLO,CYCS,CASP9
regulation of cysteine-type endopeptidase activity	17.72	BAK1,APAF1,PMAIP1,DIABLO,CYCS,CASP9
apoptotic signaling pathway	16.14	TP53,BAK1,APAF1,PARP2,PMAIP1,DIABLO,VDAC2,CYCS,CASP9
cellular response to external stimulus	11.82	TP53,BAK1,MAPKAP1,PMAIP1,MLST8,RICTOR,GCN1
response to nutrient levels	9.34	TP53,APAF1,MAPKAP1,PARP2,PMAIP1,MLST8,RICTOR,GCN1
response to extracellular stimulus	8.80	TP53,APAF1,MAPKAP1,PARP2,PMAIP1,MLST8,RICTOR,GCN1
DNA damage response	6.98	PARP1,TP53,SLFN11,BAK1,ADPRS,PARP2,PMAIP1,MLST8,CASP9

Olaparib 4μM R08 exp512

Mechanism of Action

Technical Notes

Compound References

Compound Supplier

Compound Characterization

Dose Response Curve

Screen Summary

Screen Results