Rucaparib 6.5μM R08 exp520

Rucaparib 6.5μM R08 exp520

Mechanism of Action

PARP1/2/3 inhibitor (Clovis), PARP1 mediates single-strand break repair, which can lead to replication-induced double strand breaks to form if not repaired; specifically target cancer with BRCA1, BRCA2 or PALB2 mutations; FDA granted an accelerated approval for use in cases of pretreated advanced ovarian cancer

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

Technical Notes

Protein References

PubChem Name: Rucaparib phosphate
Synonyms: AG-014699 phosphate; PF-01367338 phosphate
CAS #: 459868-92-9
PubChem CID: 9931953
IUPAC: 6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one;phosphoric acid
INCHI Name: InChI=1S/C19H18FN3O.H3O4P/c1-21-10-11-2-4-12(5-3-11)18-14-6-7-22-19(24)15-8-13(20)9-16(23-18)17(14)15;1-5(2,3)4/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24);(H3,1,2,3,4)
INCHI Key: FCCGJTKEKXUBFZ-UHFFFAOYSA-N
Molecular Weight: 421.4
Canonical SMILES: CNCC1=CC=C(C=C1)C2=C3CCNC(=O)C4=C3C(=CC(=C4)F)N2.OP(=O)(O)O
Isomeric SMILES: N/A
Molecular Formula: C19H21FN3O5P

Protein Supplier

Supplier Name: Med Chem Express
Catalog #: HY-10617
Lot #: 29562

Protein Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C19H18FN3O 324.15067; found 324.15184

Dose Response Curve

Platform ID: Rucaparib
Min: 4.0175; Max: 99.5587

IC	Concentration (µM)
IC10	3.6040
IC20	5.1380
IC30	6.5040
IC40	7.8900
IC50	9.4220
IC60	11.2500
IC70	13.6500
IC80	17.2800
IC90	24.6300

Screen Summary

Round: 08
Dose: 6.5µM
Days of incubation: 8
Doublings: 3.6
Numbers of reads: 16082760

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
36/13	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
DNPH1	-4.79	0.00
SPIDR	-3.96	0.00
PRDX1	-3.74	0.00
SWSAP1	-3.62	0.00
RAD54L	-3.57	0.00
MCM9	-3.54	0.00
C19orf40	-3.40	<0.01
APITD1	-3.39	0.00
RNF168	-3.30	0.00
OTUB1	-3.27	0.00
APITD1-CORT	-3.26	0.00
MUS81	-3.23	<0.01
POLB	-3.21	0.00
ZSWIM7	-3.17	0.00
C4orf27	-3.11	0.00
CHD1L	-3.07	0.00
VPS25	-2.92	0.13
UBE2N	-2.79	<0.01
SWI5	-2.75	<0.01
PNKP	-2.74	0.10
H2AFX	-2.73	0.01
MCM8	-2.72	0.01
ZP3	-2.70	<0.01
UBE2A	-2.69	<0.01
KPNA4	-2.65	<0.01
ESCO2	-2.62	<0.01
ITPA	-2.62	<0.01
SIVA1	-2.62	<0.01
CSK	-2.48	0.01
PSMA5	-2.47	0.12
EBF1	2.10	0.30
ODC1	2.11	0.15
SRM	2.12	0.15
PIK3R1	2.14	0.14
ASUN	2.21	0.11
NUP155	2.22	0.15
DDX39B	2.23	0.15
SLC25A32	2.26	0.15
PCIF1	2.35	0.06
RCAN3	2.37	0.10
ITPKB	2.39	0.09
GTF3A	2.41	0.24
AKT2	2.42	0.09
CD19	2.42	0.09
DPH1	2.43	0.04
APAF1	2.45	0.04
SHMT2	2.49	0.11
RHOH	2.55	0.05
HSPA5	2.64	0.33
PHC1	2.65	0.02
SLFN11	2.65	0.02
EIF4G1	2.69	0.03
ZNF330	2.71	0.03
PARP2	2.74	0.03
MLST8	2.91	<0.01
MAPKAP1	2.98	<0.01
RICTOR	3.39	<0.01
ADPRHL2	3.57	<0.01
TP53	4.88	<0.01
PARP1	7.51	<0.01

Screen	Correlation	Plot
Sulforaphane 9μM R08 exp526 no dilution day6	0.088	View
Sulforaphane 9μM R08 exp525	0.088	View
Talazoparib 0.006μM R06 exp299	0.077	View
Trimetrexate 0.03μM R08 exp535	0.057	View
Olaparib 4μM R08 exp512	0.204	View
Campthothecin 0.001μM R06 exp270	0.081	View
Diepoxybutane 3μM R07 exp354	0.076	View
AICAR 240μM R03 exp116	0.073	View
Nutlin-3A 1.6μM R06 exp294	0.071	View
Aphidicolin 0.4μM R08 exp440	0.069	View
Etoposide 0.1μM R05 exp198	0.065	View
MS023 2μM R03 exp134	0.055	View
Quercetin 20μM R08 exp517	0.055	View
Pterostilbene 16μM R02 exp78	0.054	View
Genistein 15μM R07 exp360	0.053	View
Resveratrol 16μM R03 exp147	0.052	View
ML-792 0.2μM R08 exp505	0.052	View
Lead acetate 2000μM R08 exp497	0.051	View
Lead acetate 2000μM R08 exp498 no dilution day6	0.051	View
B02 10μM R08 exp453	0.051	View

GO Term	Fold Change	Genes
MutSbeta complex binding	637.27	MCM9,MCM8
interstrand cross-link repair	74.97	MCM9,CENPS,RNF168,MCM8
recombinational repair	53.55	SPIDR,SWSAP1,RAD54L,MCM9,MUS81,ZSWIM7,UBE2N,SWI5,H2AX,MCM8
double-strand break repair via homologous recombination	49.44	SPIDR,RAD54L,MCM9,MUS81,ZSWIM7,UBE2N,SWI5,H2AX,MCM8
DNA-templated DNA replication maintenance of fidelity	48.10	MCM9,CENPS,MUS81,MCM8
double-strand break repair	44.39	SPIDR,SWSAP1,RAD54L,MCM9,RNF168,MUS81,POLB,ZSWIM7,UBE2N,SWI5,PNKP,H2AX,MCM8,ESCO2
site of double-strand break	39.34	RNF168,CHD1L,PNKP,H2AX,ESCO2
DNA recombination	37.15	SPIDR,SWSAP1,RAD54L,MCM9,CENPS,RNF168,MUS81,POLB,ZSWIM7,UBE2N,SWI5,H2AX,MCM8
site of DNA damage	29.50	RNF168,CHD1L,PNKP,H2AX,ESCO2
DNA-templated DNA replication	29.41	MCM9,CENPS,MUS81,POLB,PNKP,MCM8
response to ionizing radiation	28.97	SPIDR,RAD54L,RNF168,POLB,SWI5,H2AX
positive regulation of DNA repair	26.33	SPIDR,RNF168,UBE2N,PNKP,H2AX
DNA repair	24.46	SPIDR,SWSAP1,RAD54L,MCM9,CENPS,RNF168,OTUB1,MUS81,POLB,ZSWIM7,CHD1L,UBE2N,SWI5,PNKP,H2AX,MCM8,UBE2A,ESCO2
DNA replication	19.81	MCM9,CENPS,MUS81,POLB,PNKP,MCM8
regulation of DNA repair	19.02	SPIDR,RNF168,OTUB1,UBE2N,PNKP,H2AX
catalytic activity, acting on DNA	16.27	RAD54L,MCM9,MUS81,POLB,CHD1L,MCM8
DNA damage response	16.11	SPIDR,SWSAP1,RAD54L,MCM9,CENPS,RNF168,OTUB1,MUS81,POLB,ZSWIM7,CHD1L,UBE2N,SWI5,PNKP,H2AX,MCM8,UBE2A,ESCO2
DNA metabolic process	16.07	SPIDR,SWSAP1,RAD54L,MCM9,CENPS,RNF168,OTUB1,MUS81,POLB,ZSWIM7,CHD1L,UBE2N,SWI5,PNKP,H2AX,MCM8,UBE2A,ESCO2
response to radiation	12.46	SPIDR,RAD54L,RNF168,POLB,SWI5,PNKP,H2AX,UBE2A

GO Term	Fold Change	Genes
NAD DNA ADP-ribosyltransferase activity	552.30	PARP1,PARP2
NAD+-protein-glutamate ADP-ribosyltransferase activity	368.20	PARP1,PARP2
NAD+- protein-aspartate ADP-ribosyltransferase activity	276.15	PARP1,PARP2
TORC2 complex	207.11	RICTOR,MAPKAP1,MLST8
TOR signaling	47.34	RICTOR,MAPKAP1,MLST8
site of DNA damage	25.57	PARP1,TP53,ADPRS,PARP2,SLFN11
neuron apoptotic process	21.87	TP53,PARP2,APAF1,AKT2
cellular response to light stimulus	20.27	PARP1,TP53,AKT2,PIK3R1
positive regulation of cell growth	17.82	RICTOR,MAPKAP1,MLST8,PARP2,EIF4G1
cellular response to nutrient levels	14.22	TP53,RICTOR,MAPKAP1,MLST8,EIF4G1,HSPA5
cellular response to extracellular stimulus	12.65	TP53,RICTOR,MAPKAP1,MLST8,EIF4G1,HSPA5
cellular response to external stimulus	10.13	TP53,RICTOR,MAPKAP1,MLST8,EIF4G1,HSPA5
response to nutrient levels	9.34	TP53,RICTOR,MAPKAP1,MLST8,PARP2,EIF4G1,HSPA5,APAF1
response to extracellular stimulus	8.80	TP53,RICTOR,MAPKAP1,MLST8,PARP2,EIF4G1,HSPA5,APAF1
positive regulation of phosphorylation	6.91	TP53,RICTOR,MAPKAP1,MLST8,EIF4G1,CD19,AKT2,PDPK1
positive regulation of phosphate metabolic process	6.28	TP53,RICTOR,MAPKAP1,MLST8,EIF4G1,CD19,AKT2,PDPK1
positive regulation of phosphorus metabolic process	6.27	TP53,RICTOR,MAPKAP1,MLST8,EIF4G1,CD19,AKT2,PDPK1
negative regulation of programmed cell death	6.18	TP53,ADPRS,RICTOR,MAPKAP1,MLST8,HSPA5,AKT2,ITPKB,PIK3R1,PDPK1
negative regulation of apoptotic process	5.73	TP53,RICTOR,MAPKAP1,MLST8,HSPA5,AKT2,ITPKB,PIK3R1,PDPK1

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