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Compound Detail

CHEMBL1094636

NIRAPARIB
💊 Approved Drug
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💊 Approved Drug
NC(=O)c1cccc2cn(-c3ccc([C@@H]4CCCNC4)cc3)nc12

Basic Information

ChEMBL ID CHEMBL1094636
Name NIRAPARIB
Phase Approved
Structure Type MOL
InChI Key PCHKPVIQAHNQLW-CQSZACIVSA-N
Therapeutic ✓ Yes

Known Names

JNJ-64091742 MK-4827 MK4827 Niraparib Zejula ZL-2306
28
Targets
91
Activities
4
Assay Types
18
PK Parameters
20
Publications
6
Known Names
20
Indications
2
Mechanisms

Molecular Properties

320.4
MW (Da)
2.59
ALogP
4
HBA
2
HBD
72.9
PSA (Ų)
0.78
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2017
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Natural Product First in Class Chemical Probe
USAN Stem -parib
USAN Year 2011

Extended Properties

Molecular Formula C19H20N4O
MW 320.40
Aromatic Rings 3
Heavy Atoms 24
NP-Likeness -0.92

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Poly [ADP-ribose] polymerase 2 inhibitor INHIBITOR Poly [ADP-ribose] polymerase 2
Poly [ADP-ribose] polymerase-1 inhibitor INHIBITOR Poly [ADP-ribose] polymerase 1

Indications

Neoplasms Neoplasms Biliary Tract Neoplasms Biliary Tract Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Carcinoma, Non-Small-Cell Lung Hereditary Breast and Ovarian Cancer Syndrome Ovarian Neoplasms Ovarian Neoplasms Ovarian Neoplasms Prostatic Neoplasms, Castration-Resistant Small Cell Lung Carcinoma Carcinoma, Pancreatic Ductal Carcinoma, Squamous Cell Carcinoma, Squamous Cell Colorectal Neoplasms Endometrial Neoplasms Endometrial Neoplasms

ATC Classification

L01XK02
niraparib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 79 meas. best 8.7
EC50 6 meas. best 8.4
Kd 4 meas. best 9.0
Ki 2 meas. best 8.49

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Poly [ADP-ribose] polymerase 1
CHEMBL3105
Kd 9.0 9.0 1.0 1
Poly [ADP-ribose] polymerase 1
CHEMBL3105
IC50 8.7 7.9226 2.0 19
Poly [ADP-ribose] polymerase 2
CHEMBL5366
IC50 8.68 7.99 2.1 8
Poly [ADP-ribose] polymerase 1
CHEMBL3105
Ki 8.49 8.49 3.2 1
PARP 1, 2 and 3
CHEMBL3390820
IC50 8.46 8.43 3.5 2
Poly [ADP-ribose] polymerase 2
CHEMBL5366
Ki 8.4 8.4 4.0 1
PARP 1, 2 and 3
CHEMBL3390820
EC50 8.4 8.4 4.0 2
Ishikawa
CHEMBL614649
IC50 7.62 7.62 24.0 1
Poly [ADP-ribose] polymerase 2
CHEMBL5366
Kd 7.11 7.11 78.0 1
Protein mono-ADP-ribosyltransferase PARP12
CHEMBL2429709
IC50 7.1 6.6 79.0 2
HEC-1B cell line
CHEMBL614817
IC50 6.9 6.9 127.0 1
DLD-1
CHEMBL614285
IC50 6.83 6.83 149.0 1
Poly [ADP-ribose] polymerase 1
CHEMBL3105
EC50 6.7 5.605 200.0 2
Dual specificity tyrosine-phosphorylation-regulated kinase 1B
CHEMBL5543
IC50 6.59 6.15 254.0 2
Protein mono-ADP-ribosyltransferase PARP4
CHEMBL6142
Kd 6.57 6.57 272.0 1
Dual specificity tyrosine-phosphorylation-regulated kinase 1A
CHEMBL2292
IC50 6.53 6.185 297.0 2
Protein mono-ADP-ribosyltransferase PARP3
CHEMBL5083
IC50 6.53 6.3167 295.1 3
Protein mono-ADP-ribosyltransferase PARP4
CHEMBL6142
IC50 6.48 6.3933 330.0 3
Poly [ADP-ribose] polymerase tankyrase-1
CHEMBL6164
IC50 6.24 5.8333 570.0 3
Unchecked
CHEMBL612545
EC50 6.21 6.21 620.8 1
NON-PROTEIN TARGET
CHEMBL3879801
EC50 6.19 6.19 650.0 1
MCF7
CHEMBL387
IC50 6.1 5.6267 800.0 3
HCT-116
CHEMBL394
IC50 6.08 5.91 830.0 2
MV4-11
CHEMBL613835
IC50 5.77 5.595 1690.0 2
Protein mono-ADP-ribosyltransferase PARP14
CHEMBL2176777
IC50 5.76 5.26 1737.8 2
Protein mono-ADP-ribosyltransferase PARP10
CHEMBL2429708
IC50 5.72 5.5975 1900.0 4
A549
CHEMBL392
IC50 5.38 5.14 4170.0 2
Protein mono-ADP-ribosyltransferase PARP10
CHEMBL2429708
Kd 5.3 5.3 5000.0 1
Poly [ADP-ribose] polymerase tankyrase-2
CHEMBL6154
IC50 5.29 5.29 5128.6 2
MDA-MB-231
CHEMBL400
IC50 5.2 4.746 6320.0 5
MDA-MB-468
CHEMBL614335
IC50 5.12 5.12 7600.0 1
BT-549
CHEMBL614072
IC50 5.08 4.8467 8280.0 3
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.0 5.0 10000.0 1
NCM460
CHEMBL4483264
IC50 4.67 4.47 21130.0 2
Protein mono-ADP-ribosyltransferase PARP15
CHEMBL2176778
IC50 4.54 4.54 28840.3 2
HT-22
CHEMBL614316
IC50 4.46 4.46 35000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 28.0 mL.min-1.kg-1 Rattus norvegicus
CL 4.0 mL.min-1.g-1 Mus musculus
CL 16.0 mL.min-1.g-1 Rattus norvegicus
CL 0.3 mL.min-1.g-1 Rattus norvegicus
CL 31.0 mL.min-1.kg-1 Canis lupus familiaris
CL 16.0 uL/min Homo sapiens
CL 28.0 mL.min-1.kg-1 Rattus norvegicus
Cmax 2000.0 nM Homo sapiens
F 65.0 % Rattus norvegicus
F 57.0 % Canis lupus familiaris
F 65.0 % Rattus norvegicus
Fu 0.26 - Mus musculus
Fu 0.16 - Homo sapiens
T1/2 36.4 hr Homo sapiens
T1/2 5.7 hr Canis lupus familiaris
T1/2 3.4 hr Rattus norvegicus
T1/2 36.4 hr Homo sapiens
T1/2 36.0 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Poly [ADP-ribose] polymerase 1 Kd = 1.0 nM 9.0 Binding affinity to PARP1 (unknown origin) assessed as apparent dissociation con... 34570508
Poly [ADP-ribose] polymerase 1 IC50 = 2.0 nM 8.7 Inhibition of PARP1 (unknown origin) 25761096
Poly [ADP-ribose] polymerase 2 IC50 = 2.1 nM 8.68 Inhibition of human PARP2 by trichloroacetic acid precipitation assay 19873981
Poly [ADP-ribose] polymerase 2 IC50 = 2.1 nM 8.68 Inhibition of PARP2 (unknown origin) 30684797
Poly [ADP-ribose] polymerase 2 IC50 = 2.1 nM 8.68 Inhibition of PARP2 (unknown origin) 35051747
Poly [ADP-ribose] polymerase 2 IC50 = 2.1 nM 8.68 Inhibition of PARP2 (unknown origin) 37843892
Poly [ADP-ribose] polymerase 1 Ki = 3.2 nM 8.49 Inhibition of PARP1 (unknown origin) 30684797
Poly [ADP-ribose] polymerase 1 IC50 = 3.2 nM 8.49 Inhibition of human PARP1 by SPA 19873981
PARP 1, 2 and 3 IC50 = 3.5 nM 8.46 Inhibition of PARP in BRCA2-deficient human CAPAN-1 cells assessed as inhibition... 25761096
Poly [ADP-ribose] polymerase 1 IC50 = 3.8 nM 8.42 Inhibition of PARP1 (unknown origin) 37843892
Poly [ADP-ribose] polymerase 1 IC50 = 3.8 nM 8.42 Inhibition of PARP1 (unknown origin) 38477575
Poly [ADP-ribose] polymerase 1 IC50 = 3.8 nM 8.42 Inhibition of PARP1 (unknown origin) 27353531
Poly [ADP-ribose] polymerase 1 IC50 = 3.8 nM 8.42 Inhibition of PARP1 (unknown origin) 30684797
Poly [ADP-ribose] polymerase 1 IC50 = 3.8 nM 8.42 Inhibition of PARP1 (unknown origin) 35051747
Poly [ADP-ribose] polymerase 2 Ki = 4.0 nM 8.4 Inhibition of PARP2 (unknown origin) 30684797
PARP 1, 2 and 3 EC50 = 4.0 nM 8.4 Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inh... 19873981
PARP 1, 2 and 3 IC50 = 4.0 nM 8.4 Inhibition of PARP in human A2780 cells assessed as inhibition of hydrogen perox... 25761096
PARP 1, 2 and 3 EC50 = 4.0 nM 8.4 Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxi... 25761096
Poly [ADP-ribose] polymerase 1 IC50 = 4.67 nM 8.33 Inhibition of PARP1 (unknown origin) incubated for 70 mins by HT universal chemi... 38134746
Poly [ADP-ribose] polymerase 1 IC50 = 8.05 nM 8.09 Inhibition of human PARP1 using [3H]NAD as substrate after 1 min by microplate s... 26652717

Literature References

PubMed DOI Target Context # Activities
25761096 10.1021/jm5018237 NON-PROTEIN TARGET 10
25761096 10.1021/jm5018237 PARP 1, 2 and 3 9
25761096 10.1021/jm5018237 ADMET 9
38134746 10.1016/j.ejmech.2023.116054 MDA-MB-231 8
25761096 10.1021/jm5018237 Plasma 6
25761096 10.1021/jm5018237 Rattus norvegicus 6
24893124 10.1021/jm500415t Homo sapiens 5
25761096 10.1021/jm5018237 Canis familiaris 5
36989813 10.1016/j.ejmech.2023.115300 No relevant target 5
28001384 10.1021/acs.jmedchem.6b00990 Poly [ADP-ribose] polymerase 1 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
23850199 10.1016/j.bmcl.2013.06.055 Poly [ADP-ribose] polymerase 1 4
28001384 10.1021/acs.jmedchem.6b00990 Protein mono-ADP-ribosyltransferase PARP10 4
19873981 10.1021/jm901188v Mus musculus 4
19873981 10.1021/jm901188v Unchecked 3
34570508 10.1021/acs.jmedchem.1c01012 Poly [ADP-ribose] polymerase 1 3
25761096 10.1021/jm5018237 A549 3
19873981 10.1021/jm901188v NON-PROTEIN TARGET 3
37832229 10.1016/j.ejmech.2023.115843 HCT-116 3
37468498 10.1038/s41467-023-40064-9 Alpha-1A adrenergic receptor 3

Data from ChEMBL 36 via Core Engine