Compound Detail

CHEMBL521686

OLAPARIB

💊 Approved Drug

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💊 Approved Drug

O=C(c1cc(Cc2n[nH]c(=O)c3ccccc23)ccc1F)N1CCN(C(=O)C2CC2)CC1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL521686
Name	OLAPARIB
Phase	Approved
Structure Type	MOL
InChI Key	FDLYAMZZIXQODN-UHFFFAOYSA-N
Therapeutic	✓ Yes

Known Names

AZ-2281 AZ2281 AZD-2281 AZD2281 KU-0059436 KU-59436 Lynparza NSC-747856 Olaparib OLAPARIB COMPONENT OF KEYLYNK-010

298

Targets

997

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

434.5

MW (Da)

2.35

ALogP

HBA

HBD

86.4

PSA (Å²)

0.68

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2014
Availability	Prescription
Chirality	Achiral

Routes of Administration

Oral

Flags

First in Class Chemical Probe

USAN Stem	-parib
USAN Year	2013

Extended Properties

Molecular Formula	C24H23FN4O3
MW	434.47
Aromatic Rings	3
Heavy Atoms	32
NP-Likeness	-1.61

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
PARP 1, 2 and 3 inhibitor	INHIBITOR	PARP 1, 2 and 3	✓	✓

Indications

Breast Neoplasms Breast Neoplasms Breast Neoplasms Neoplasms Neoplasms Ovarian Neoplasms Ovarian Neoplasms Ovarian Neoplasms Pancreatic Neoplasms Pancreatic Neoplasms Prostatic Neoplasms, Castration-Resistant Prostatic Neoplasms, Castration-Resistant Carcinoma Carcinoma, Non-Small-Cell Lung Endometrial Neoplasms Endometrial Neoplasms Endometrial Neoplasms Lung Neoplasms Lung Neoplasms Prostatic Neoplasms

ATC Classification

L01XK01

olaparib

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 967 meas. best 10.0

EC50 19 meas. best 9.4

Kd 10 meas. best 9.62

Ki 1 meas. best 9.1

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Poly [ADP-ribose] polymerase 1 CHEMBL3105	IC50	10.0	8.2433	0.1	107
Poly [ADP-ribose] polymerase 2 CHEMBL5366	IC50	10.0	8.7903	0.1	39
Poly [ADP-ribose] polymerase 1 CHEMBL3105	Kd	9.62	8.3775	0.2	4
Poly [ADP-ribose] polymerase 2 CHEMBL5366	Kd	9.57	9.4733	0.3	3
Poly [ADP-ribose] polymerase 1 CHEMBL3105	EC50	9.4	7.505	0.4	4
Poly [ADP-ribose] polymerase 1 CHEMBL3105	Ki	9.1	9.1	0.8	1
PARP 1, 2 and 3 CHEMBL3390820	EC50	8.45	8.45	3.6	1
Poly [ADP-ribose] polymerase tankyrase-2 CHEMBL6154	IC50	8.28	6.06	5.2	8
Protein mono-ADP-ribosyltransferase PARP3 CHEMBL5083	Kd	8.24	8.24	5.8	1
SW-620 CHEMBL612262	IC50	8.22	6.605	6.0	2
PEO1 CHEMBL4296485	IC50	8.19	8.19	6.4	1
MX1 CHEMBL613704	IC50	8.08	5.66	8.3	3
Protein mono-ADP-ribosyltransferase PARP3 CHEMBL5083	IC50	8.07	7.1229	8.6	7
Unchecked CHEMBL612545	IC50	7.98	5.7321	10.4	14
Poly [ADP-ribose] polymerase tankyrase-1 CHEMBL6164	IC50	7.98	6.0027	10.4	11
Protein mono-ADP-ribosyltransferase PARP4 CHEMBL6142	IC50	7.87	6.8833	13.5	3
MDA-MB-436 CHEMBL4296465	IC50	7.75	6.4033	18.0	15
PARP 1, 2 and 3 CHEMBL3390820	IC50	7.68	7.68	20.9	1
MX1 CHEMBL613704	EC50	7.63	7.63	23.2	1
CAPAN-1 CHEMBL614536	IC50	7.57	5.716	27.0	15
Olaparib-resistant CAPAN-1 CHEMBL6066794	IC50	7.4	7.4	40.0	1
DLD-1 CHEMBL614285	IC50	7.38	5.538	42.0	10
DLD-1 CHEMBL614285	EC50	7.0	5.86	100.0	2
Protein mono-ADP-ribosyltransferase PARP6 CHEMBL2380187	IC50	6.92	6.0433	120.0	3
Protein mono-ADP-ribosyltransferase PARP4 CHEMBL6142	Kd	6.85	6.85	141.0	1
Unchecked CHEMBL612545	EC50	6.7	6.2167	200.0	3
Protein mono-ADP-ribosyltransferase PARP8 CHEMBL3091262	IC50	6.62	6.185	240.0	2
NON-PROTEIN TARGET CHEMBL3879801	EC50	6.59	6.59	259.0	1
Protein mono-ADP-ribosyltransferase PARP10 CHEMBL2429708	IC50	6.46	5.8157	350.0	7
SUM149PT CHEMBL4296497	EC50	6.4	5.78	400.0	2
COLO-800 CHEMBL2366224	IC50	6.36	6.36	441.6	1
Olaparib-resistant PEO1 CHEMBL6066795	IC50	6.29	6.1	506.7	2
EOL1 CHEMBL614489	IC50	6.25	6.25	564.5	1
MDA-MB-468 CHEMBL614335	IC50	6.22	5.3208	600.0	12
Protein mono-ADP-ribosyltransferase TIPARP CHEMBL2380188	IC50	6.2	5.765	631.0	2
Protein mono-ADP-ribosyltransferase PARP12 CHEMBL2429709	IC50	6.16	5.52	690.0	4
MDA-MB-231 CHEMBL400	IC50	6.16	4.928	690.0	20
A2780 CHEMBL614004	IC50	6.13	5.4733	741.3	3
NCI-H209 CHEMBL2366365	IC50	6.04	6.04	915.6	1
ES1 CHEMBL2366146	IC50	5.95	5.95	1114.1	1
NKM-1 CHEMBL2366133	IC50	5.9	5.9	1253.5	1
NTERA-2-cl-D1 CHEMBL614206	IC50	5.88	5.88	1333.4	1
HCT-116 CHEMBL394	IC50	5.86	5.1931	1370.0	16
MHH-ES-1 CHEMBL1075505	IC50	5.79	5.79	1620.7	1
Jurkat CHEMBL397	IC50	5.77	5.77	1698.2	1
ES8 CHEMBL2366069	IC50	5.76	5.76	1724.1	1
ES-2 CHEMBL5058622	IC50	5.69	5.69	2050.0	1
NCI-H720 CHEMBL2366105	IC50	5.66	5.66	2207.0	1
EW-3 CHEMBL2366307	IC50	5.64	5.64	2275.3	1
MCF7 CHEMBL387	IC50	5.63	4.725	2330.0	8

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	5066.67	ng.hr.mL-1	Rattus norvegicus
AUC	8516.67	ng.hr.mL-1	Canis lupus familiaris
AUC	559.0	ng.hr.mL-1	Rattus norvegicus
AUC	5500.3	ng.hr.mL-1	Rattus norvegicus
AUC	4989.5	ng.hr.mL-1	Rattus norvegicus
CL	49.0	mL.min-1.kg-1	Rattus norvegicus
CL	5.4	mL.min-1.kg-1	Canis lupus familiaris
CL	29.0	mL.min-1.g-1	Homo sapiens
CL	34.3	mL.min-1.kg-1	Rattus norvegicus
CL	30.0	mL.min-1.kg-1	Rattus norvegicus
CL	34.3	mL.min-1.kg-1	Rattus norvegicus
Cmax	5984.3	nM	Homo sapiens
Cmax	1005.82	nM	Rattus norvegicus
Cmax	28287.34	nM	Rattus norvegicus
Cmax	5972.79	nM	Rattus norvegicus
F	100.0	%	Rattus norvegicus
F	100.0	%	Canis lupus familiaris
F	11.0	%	Rattus norvegicus
F	45.4	%	Rattus norvegicus
F	10.0	%	Rattus norvegicus
T1/2	0.8833	hr	Rattus norvegicus
T1/2	2.833	hr	Canis lupus familiaris
T1/2	7.0	hr	Homo sapiens
T1/2	0.852	hr	Homo sapiens
T1/2	0.29	hr	Homo sapiens
T1/2	0.53	hr	Rattus norvegicus
T1/2	1.1	hr	Rattus norvegicus
T1/2	1.0	hr	Rattus norvegicus
T1/2	0.53	hr	Rattus norvegicus
T1/2	0.852	hr	Felis catus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Poly [ADP-ribose] polymerase 1	IC50	=	0.1	nM	10.0	Inhibition of PARP1 (unknown origin) using histone/NAD+ as substrates by NAD/NAD...	38776806
Poly [ADP-ribose] polymerase 2	IC50	=	0.1	nM	10.0	Inhibition of PARP-2 (unknown origin)	36343904
Poly [ADP-ribose] polymerase 2	IC50	=	0.11	nM	9.96	Inhibition of PARP2 (unknown origin) using histone/NAD+ as substrates by NAD/NAD...	38776806
Poly [ADP-ribose] polymerase 2	IC50	=	0.13	nM	9.89	Inhibition of N-terminal GST-tagged human PARP2 (2 to 583 residues) expressed in...	37752013
Poly [ADP-ribose] polymerase 1	Kd	=	0.24	nM	9.62	Binding affinity to recombinant human HisGST-tagged PARP-1 catalytic domain by s...	26222319
Poly [ADP-ribose] polymerase 2	Kd	=	0.27	nM	9.57	Binding affinity to recombinant human PARP-2 by SPR analysis	34404206
Poly [ADP-ribose] polymerase 2	Kd	=	0.28	nM	9.55	Binding affinity to recombinant human HisGST-tagged PARP-2 catalytic domain by s...	26222319
Poly [ADP-ribose] polymerase 2	IC50	=	0.3	nM	9.52	Inhibition of PARP2 (unknown origin)	38375763
Poly [ADP-ribose] polymerase 1	Kd	=	0.31	nM	9.51	Binding affinity to recombinant human PARP-1 by SPR analysis	34404206
Poly [ADP-ribose] polymerase 1	EC50	=	0.4	nM	9.4	Inhibition of PARP-1 in human HeLa cells incubated for 18 hrs in presence of H2O...	33264017
Poly [ADP-ribose] polymerase 2	IC50	=	0.3981	nM	9.4	Inhibition of human N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in...	31042381
Poly [ADP-ribose] polymerase 2	IC50	=	0.4	nM	9.4	Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition ...	33264017
Poly [ADP-ribose] polymerase 1	IC50	=	0.4	nM	9.4	Inhibition of human PARP1 incubated for 90 mins by colorimetric assay	38375763
Poly [ADP-ribose] polymerase 1	IC50	=	0.411	nM	9.39	Inhibition of C-terminal His-tagged human recombinant PARP-1 (1 to 1014 residues...	37484567
Poly [ADP-ribose] polymerase 2	IC50	=	0.45	nM	9.35	Enzyme Assay: In order to test the selectivity of substituents on piperazinotria...	-
Poly [ADP-ribose] polymerase 2	Kd	=	0.5	nM	9.3	Binding affinity to PARP2 (unknown origin) assessed as apparent dissociation con...	34570508
Poly [ADP-ribose] polymerase 2	IC50	=	0.5	nM	9.3	Inhibition of human N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in...	31042381
Poly [ADP-ribose] polymerase 1	IC50	=	0.5	nM	9.3	Inhibition of PARP-1 (unknown origin) using Femto-ECL as substrate preincubated ...	38039793
Poly [ADP-ribose] polymerase 2	IC50	=	0.5	nM	9.3	Inhibition of N-terminal GST-tagged human PARP2 (2 to 583 residues) expressed in...	33120078
Poly [ADP-ribose] polymerase 1	IC50	=	0.51	nM	9.29	Inhibition of N-terminal GST-tagged full length human PARP1 (2 to 1014 residues)...	37752013

Literature References

PubMed	DOI	Target Context	# Activities
35091172	10.1016/j.ejmech.2022.114116	Unchecked	49
37616488	10.1021/acs.jmedchem.3c00640	MDA-MB-231	40
38375763	10.1021/acs.jmedchem.3c02096	MDA-MB-436	35
37616488	10.1021/acs.jmedchem.3c00640	MCF7	25
27177826	10.1016/j.bmcl.2016.04.090	K562	25
31775874	10.1186/s13148-019-0758-2	Olaparib-resistant PEO1	21
34813314	10.1021/acs.jmedchem.1c01535	Unchecked	18
34813314	10.1021/acs.jmedchem.1c01535	SW1990	17
35780655	10.1016/j.bmc.2022.116908	MDA-MB-231	16
38477575	10.1021/acs.jmedchem.4c00077	MDA-MB-231	14
35091172	10.1016/j.ejmech.2022.114116	SW1990	12
28692916	10.1016/j.ejmech.2017.06.053	MDA-MB-436	11
39229909	10.1021/acs.jmedchem.4c01412	MDA-MB-468	10
38375763	10.1021/acs.jmedchem.3c02096	MDA-MB-231	10
35785724	10.1016/j.ejmech.2022.114574	CAPAN-1	9
35504210	10.1016/j.ejmech.2022.114417	HCT-116	9
37605459	10.1021/acs.jmedchem.3c00821	Unchecked	9
28692916	10.1016/j.ejmech.2017.06.053	Rattus norvegicus	9
32924477	10.1021/acs.jmedchem.0c00821	Protein cereblon/PARP1	8
31775874	10.1186/s13148-019-0758-2	Unchecked	8

Data from ChEMBL 36 via Core Engine