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Compound Detail

CHEMBL4112930

PAMIPARIB
🧪 Phase III
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🧪 Phase III
C[C@]12CCCN1CC1=NNC(=O)c3cc(F)cc4[nH]c2c1c34

Basic Information

ChEMBL ID CHEMBL4112930
Name PAMIPARIB
Phase Phase III
Structure Type MOL
InChI Key DENYZIUJOTUUNY-MRXNPFEDSA-N

Known Names

Bgb-290 Pamiparib
17
Targets
38
Activities
2
Assay Types
30
PK Parameters
20
Publications
2
Known Names
13
Indications
2
Mechanisms

Molecular Properties

298.3
MW (Da)
2.08
ALogP
3
HBA
2
HBD
60.5
PSA (Ų)
0.78
QED
0
Ro5 Violations
0
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer
USAN Stem -parib
USAN Year 2018

Extended Properties

Molecular Formula C16H15FN4O
MW 298.32
Aromatic Rings 2
Heavy Atoms 22
NP-Likeness -0.10

Mechanism of Action

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

Indications

Neoplasms Neoplasms Biliary Tract Neoplasms Breast Neoplasms Ovarian Neoplasms Prostatic Neoplasms Prostatic Neoplasms, Castration-Resistant Small Cell Lung Carcinoma Stomach Neoplasms Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Central Nervous System Neoplasms Glioblastoma

ATC Classification

L01XK06
pamiparib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 33 meas. best 9.96
EC50 5 meas. best 9.7

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Poly [ADP-ribose] polymerase 2
CHEMBL5366
IC50 9.96 9.374 0.1 5
Poly [ADP-ribose] polymerase 1
CHEMBL3105
EC50 9.7 8.795 0.2 2
Poly [ADP-ribose] polymerase 1
CHEMBL3105
IC50 9.08 8.8583 0.8 6
MDA-MB-436
CHEMBL4296465
EC50 7.97 7.97 10.6 1
HCC1395
CHEMBL1075454
EC50 7.37 7.37 42.5 1
Unchecked
CHEMBL612545
EC50 7.27 7.27 53.8 1
Protein mono-ADP-ribosyltransferase PARP3
CHEMBL5083
IC50 7.17 6.95 68.0 2
Poly [ADP-ribose] polymerase tankyrase-2
CHEMBL6154
IC50 6.85 6.485 140.0 2
Poly [ADP-ribose] polymerase tankyrase-1
CHEMBL6164
IC50 6.64 6.64 230.0 1
Unchecked
CHEMBL612545
IC50 6.3 6.3 500.0 1
Protein mono-ADP-ribosyltransferase PARP12
CHEMBL2429709
IC50 5.62 5.62 2400.0 1
Protein mono-ADP-ribosyltransferase PARP11
CHEMBL2380189
IC50 5.57 5.57 2700.0 1
Protein mono-ADP-ribosyltransferase PARP8
CHEMBL3091262
IC50 5.08 5.08 8400.0 1
Protein mono-ADP-ribosyltransferase PARP10
CHEMBL2429708
IC50 4.96 4.96 11000.0 1
Protein mono-ADP-ribosyltransferase TIPARP
CHEMBL2380188
IC50 4.96 4.96 11000.0 1
Solute carrier organic anion transporter family member 1B3
CHEMBL1743121
IC50 4.71 4.71 19400.0 1
Solute carrier organic anion transporter family member 1B1
CHEMBL1697668
IC50 4.71 4.71 19400.0 1
Organic anion transporter 3
CHEMBL1641348
IC50 4.62 4.62 23900.0 1
Solute carrier family 22 member 6
CHEMBL1641347
IC50 4.32 4.32 47800.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 1600.0 ng.hr.mL-1 Canis lupus familiaris
AUC 1085.0 ng.hr.mL-1 Canis lupus familiaris
AUC 3469.0 ng.hr.mL-1 Rattus norvegicus
AUC 1482.0 ng.hr.mL-1 Rattus norvegicus
AUC 5521.0 ng.hr.mL-1 Mus musculus
AUC 1757.0 ng.hr.mL-1 Mus musculus
CL 15.2 mL.min-1.kg-1 Canis lupus familiaris
CL 22.7 mL.min-1.kg-1 Rattus norvegicus
CL 29.9 mL.min-1.kg-1 Mus musculus
CL 7.2 mL.min-1.g-1 Rattus norvegicus
CL 9.5 mL.min-1.g-1 Canis lupus familiaris
CL 7.9 mL.min-1.g-1 Homo sapiens
CL 12.9 mL.min-1.kg-1 Mus musculus
Cmax 1682.76 nM Canis lupus familiaris
Cmax 2886.16 nM Rattus norvegicus
Cmax 9094.26 nM Mus musculus
F 72.6 % Canis lupus familiaris
F 98.7 % Mus musculus
F 93.7 % Rattus norvegicus
Fu 0.21 - Canis lupus familiaris
Fu 0.151 - Rattus norvegicus
Fu 0.15 - Mus musculus
Fu 0.043 - Homo sapiens
T1/2 3.62 hr Canis lupus familiaris
T1/2 2.07 hr Canis lupus familiaris
T1/2 5.5 hr Rattus norvegicus
T1/2 5.3 hr Rattus norvegicus
T1/2 3.16 hr Mus musculus
T1/2 3.95 hr Mus musculus
Tmax 0.417 hr Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Poly [ADP-ribose] polymerase 2 IC50 = 0.11 nM 9.96 Inhibition of PARP-2 (unknown origin) 27416328
Poly [ADP-ribose] polymerase 1 EC50 = 0.2 nM 9.7 Inhibition of PARP-1 in human HeLa cells incubated for 18 hrs in presence of H2O... 33264017
Poly [ADP-ribose] polymerase 2 IC50 = 0.3 nM 9.52 Inhibition of PARP2 (unknown origin) 37843892
Poly [ADP-ribose] polymerase 2 IC50 = 0.5 nM 9.3 PARP-2 and PARP-3 Enzymatic Assay: PARP-2 and PARP-3 enzymatic assays were condu... -
Poly [ADP-ribose] polymerase 1 IC50 = 0.83 nM 9.08 Inhibition of PARP-1 (unknown origin) 27416328
Poly [ADP-ribose] polymerase 1 IC50 = 0.9 nM 9.05 PARP-1 Enzymatic Assay: PARP-1 enzymatic assay was conducted using a method modi... -
Poly [ADP-ribose] polymerase 2 IC50 = 0.9 nM 9.05 Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition ... 33264017
Poly [ADP-ribose] polymerase 1 IC50 = 0.9 nM 9.05 Inhibition of PARP1 (unknown origin) 38477575
Poly [ADP-ribose] polymerase 2 IC50 = 0.92 nM 9.04 Inhibition of human PARP2 38838546
Poly [ADP-ribose] polymerase 1 IC50 = 1.3 nM 8.89 Inhibition of human PARP1 38838546
Poly [ADP-ribose] polymerase 1 IC50 = 1.3 nM 8.89 Inhibition of human PARP-1 catalytic domain (662 to 1011 residues) expressed in ... 33264017
Poly [ADP-ribose] polymerase 1 IC50 = 6.5 nM 8.19 Inhibition of PARP1 (unknown origin) 37843892
MDA-MB-436 EC50 = 10.6 nM 7.97 Antiproliferation activity against human MDA-MB-436 cells expressing BRCA1 mutan... 33264017
Poly [ADP-ribose] polymerase 1 EC50 = 13.0 nM 7.89 Inhibition of human PARP-1 catalytic domain (662 to 1011 residues) expressed in ... 33264017
HCC1395 EC50 = 42.5 nM 7.37 Antiproliferation activity against human HCC1395 cells expressing BRCA1 mutant i... 33264017
Unchecked EC50 = 53.8 nM 7.27 Antiproliferation activity against human UWB1289 cells expressing BRCA1 mutant i... 33264017
Protein mono-ADP-ribosyltransferase PARP3 IC50 = 68.0 nM 7.17 Inhibition of PARP-3 (unknown origin) pre-incubated for 30 mins before addition ... 33264017
Poly [ADP-ribose] polymerase tankyrase-2 IC50 = 140.0 nM 6.85 Inhibition of TNKS-2 (unknown origin) pre-incubated for 30 mins before addition ... 33264017
Protein mono-ADP-ribosyltransferase PARP3 IC50 = 185.0 nM 6.73 PARP-2 and PARP-3 Enzymatic Assay: PARP-2 and PARP-3 enzymatic assays were condu... -
Poly [ADP-ribose] polymerase tankyrase-1 IC50 = 230.0 nM 6.64 Inhibition of TNKS-1 (unknown origin) pre-incubated for 30 mins before addition ... 33264017

Literature References

PubMed DOI Target Context # Activities
33264017 10.1021/acs.jmedchem.0c01346 ADMET 50
33264017 10.1021/acs.jmedchem.0c01346 Unchecked 9
33264017 10.1021/acs.jmedchem.0c01346 Poly [ADP-ribose] polymerase 1 4
33264017 10.1021/acs.jmedchem.0c01346 NCI-H209 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 2
33264017 10.1021/acs.jmedchem.0c01346 Broad substrate specificity ATP-binding cassette transporter ABCG2 2
33264017 10.1021/acs.jmedchem.0c01346 MDA-MB-436 2
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
33264017 10.1021/acs.jmedchem.0c01346 Organic anion transporter 3 1
33264017 10.1021/acs.jmedchem.0c01346 Solute carrier organic anion transporter family member 1B3 1
33264017 10.1021/acs.jmedchem.0c01346 Solute carrier family 22 member 6 1
33264017 10.1021/acs.jmedchem.0c01346 Solute carrier organic anion transporter family member 1B1 1
33264017 10.1021/acs.jmedchem.0c01346 POU domain, class 2, transcription factor 2 1
33264017 10.1021/acs.jmedchem.0c01346 SK-BR-3 1
33264017 10.1021/acs.jmedchem.0c01346 MDA-MB-231 1
33264017 10.1021/acs.jmedchem.0c01346 HCC1395 1
33264017 10.1021/acs.jmedchem.0c01346 Cytochrome P450 3A4 1
33264017 10.1021/acs.jmedchem.0c01346 Cytochrome P450 2D6 1
33264017 10.1021/acs.jmedchem.0c01346 Cytochrome P450 2C19 1
- 10.6019/CHEMBL5724796 Bromodomain-containing protein 4 1

Data from ChEMBL 36 via Core Engine