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Compound Detail

CHEMBL506871

VELIPARIB
🧪 Phase III
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🧪 Phase III
C[C@]1(c2nc3c(C(N)=O)cccc3[nH]2)CCCN1

Basic Information

ChEMBL ID CHEMBL506871
Name VELIPARIB
Phase Phase III
Structure Type MOL
InChI Key JNAHVYVRKWKWKQ-CYBMUJFWSA-N

Known Names

ABT-888 PARP-1 INHIBITOR ABT-888 Veliparib
165
Targets
663
Activities
4
Assay Types
23
PK Parameters
20
Publications
3
Known Names
20
Indications
1
Mechanisms

Molecular Properties

244.3
MW (Da)
1.26
ALogP
3
HBA
3
HBD
83.8
PSA (Ų)
0.74
QED
0
Ro5 Violations
2
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Flags

Natural Product Chemical Probe
USAN Stem -parib
USAN Year 2009

Extended Properties

Molecular Formula C13H16N4O
MW 244.30
Aromatic Rings 2
Heavy Atoms 18
NP-Likeness -0.08

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 Carcinoma, Non-Small-Cell Lung Neoplasms Neoplasms Ovarian Neoplasms Ovarian Neoplasms Ovarian Neoplasms Astrocytoma Carcinoma, Hepatocellular Colorectal Neoplasms Fallopian Tube Neoplasms Glioma Gliosarcoma Hemangiosarcoma Hereditary Breast and Ovarian Cancer Syndrome Melanoma Melanoma Pancreatic Neoplasms

ATC Classification

L01XK05
veliparib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 640 meas. best 10.21
EC50 8 meas. best 8.7
Ki 8 meas. best 8.54
Kd 7 meas. best 8.77

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Poly [ADP-ribose] polymerase 1
CHEMBL3105
IC50 10.21 8.1219 0.1 27
Poly [ADP-ribose] polymerase 2
CHEMBL5366
IC50 8.89 7.6367 1.3 9
Poly [ADP-ribose] polymerase 1
CHEMBL3105
Kd 8.77 8.655 1.7 2
Poly [ADP-ribose] polymerase 1
CHEMBL3105
EC50 8.7 7.33 2.0 4
Poly [ADP-ribose] polymerase 2
CHEMBL5366
Ki 8.54 8.2 2.9 3
Poly [ADP-ribose] polymerase 1
CHEMBL3105
Ki 8.48 8.328 3.3 5
Poly [ADP-ribose] polymerase 2
CHEMBL5366
Kd 8.24 8.1 5.8 2
PARP 1, 2 and 3
CHEMBL3390820
EC50 8.23 8.23 5.9 1
Protein mono-ADP-ribosyltransferase PARP4
CHEMBL6142
Kd 6.98 6.98 105.0 1
Protein mono-ADP-ribosyltransferase PARP3
CHEMBL5083
Kd 6.64 6.64 231.0 1
Unchecked
CHEMBL612545
IC50 6.26 5.36 550.0 2
DLD-1
CHEMBL614285
IC50 6.12 5.11 750.0 3
EOL1
CHEMBL614489
IC50 5.97 5.97 1079.8 1
Protein mono-ADP-ribosyltransferase PARP10
CHEMBL2429708
IC50 5.72 5.04 1900.0 4
Protein mono-ADP-ribosyltransferase PARP3
CHEMBL5083
IC50 5.69 5.68 2040.0 2
SNU-5
CHEMBL614934
IC50 5.5 5.5 3128.4 1
Protein mono-ADP-ribosyltransferase PARP4
CHEMBL6142
IC50 5.46 5.46 3467.4 2
BV-173
CHEMBL2366145
IC50 5.26 5.26 5454.1 1
HCC1806
CHEMBL1075457
IC50 5.24 5.24 5751.7 1
COLO-680N
CHEMBL1075427
IC50 5.21 5.21 6214.1 1
Protein mono-ADP-ribosyltransferase PARP10
CHEMBL2429708
Kd 5.17 5.17 6800.0 1
HCC2218
CHEMBL2366221
IC50 5.11 5.11 7797.0 1
SK-MEL-24
CHEMBL2366314
IC50 5.11 5.11 7819.2 1
NCI-H720
CHEMBL2366105
IC50 5.07 5.07 8436.0 1
Kasumi 1
CHEMBL613988
IC50 5.05 5.05 8892.7 1
HAL-01
CHEMBL2366142
IC50 5.0 5.0 9886.2 1
CAL-33
CHEMBL1075409
IC50 4.98 4.98 10434.0 1
Poly [ADP-ribose] polymerase tankyrase-1
CHEMBL6164
IC50 4.97 4.97 10715.2 2
Ramos-2G6-4C10
CHEMBL2366170
IC50 4.9 4.9 12475.2 1
KY821
CHEMBL2366190
IC50 4.9 4.9 12485.0 1
SK-MEL-1
CHEMBL614916
IC50 4.9 4.9 12466.3 1
HEC-1
CHEMBL1075462
IC50 4.89 4.89 12919.6 1
SK-NEP-1
CHEMBL1075580
IC50 4.88 4.88 13166.0 1
MN-60
CHEMBL2366070
IC50 4.87 4.87 13538.9 1
HepG2
CHEMBL395
IC50 4.86 4.86 13690.0 1
DU-145
CHEMBL613508
IC50 4.86 4.86 13905.3 1
EW-3
CHEMBL2366307
IC50 4.84 4.84 14556.5 1
A549
CHEMBL392
IC50 4.82 4.82 15220.0 1
OS-RC-2
CHEMBL2366188
IC50 4.8 4.8 15958.9 1
HGC-27
CHEMBL1075463
IC50 4.79 4.79 16030.0 1
RPMI-8226
CHEMBL614882
IC50 4.79 4.79 16204.2 1
ChaGo-K-1
CHEMBL1075421
IC50 4.78 4.78 16532.5 1
DEL
CHEMBL2366186
IC50 4.78 4.78 16671.7 1
GP5d
CHEMBL1075450
IC50 4.77 4.77 17053.0 1
COLO-668
CHEMBL2366215
IC50 4.75 4.75 17629.3 1
HeLa
CHEMBL399
IC50 4.74 4.74 18110.0 1
H9
CHEMBL614806
IC50 4.74 4.74 18283.3 1
NKM-1
CHEMBL2366133
IC50 4.73 4.73 18511.9 1
KYSE-150 cell line
CHEMBL613998
IC50 4.72 4.72 18998.6 1
Daoy
CHEMBL612519
IC50 4.71 4.71 19564.9 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 2200.0 ng.hr.mL-1 Mus musculus
AUC 1500.0 ng.hr.mL-1 Rattus norvegicus
AUC 3200.0 ng.hr.mL-1 Canis lupus familiaris
AUC 1300.0 ng.hr.mL-1 Macaca fascicularis
CL 68.33 mL.min-1.kg-1 Mus musculus
CL 33.33 mL.min-1.kg-1 Rattus norvegicus
CL 10.0 mL.min-1.kg-1 Canis lupus familiaris
CL 18.33 mL.min-1.kg-1 Macaca fascicularis
Cmax 6549.32 nM Mus musculus
Cmax 2046.66 nM Rattus norvegicus
Cmax 3274.66 nM Canis lupus familiaris
Cmax 1228.0 nM Macaca fascicularis
F 92.0 % Mus musculus
F 61.0 % Rattus norvegicus
F 72.0 % Canis lupus familiaris
F 56.0 % Macaca fascicularis
T1/2 1.6 hr Mus musculus
T1/2 1.2 hr Rattus norvegicus
T1/2 2.7 hr Canis lupus familiaris
T1/2 1.9 hr Macaca fascicularis
T1/2 5.0 hr Homo sapiens
T1/2 0.0255 hr Homo sapiens
T1/2 0.01833 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Poly [ADP-ribose] polymerase 1 IC50 = 0.061 nM 10.21 Inhibition of PARP1 (unknown origin) 36989813
Poly [ADP-ribose] polymerase 1 IC50 = 1.0 nM 9.0 Inhibition of PARP1 (unknown origin) 27353531
Poly [ADP-ribose] polymerase 1 IC50 = 1.1 nM 8.96 Inhibition of PARP-1 (unknown origin) after 1 hr in presence of NAD+/biotinylate... 27561983
Poly [ADP-ribose] polymerase 2 IC50 = 1.3 nM 8.89 Inhibition of PARP-2 (unknown origin) after 1 hr in presence of NAD+/biotinylate... 27561983
Poly [ADP-ribose] polymerase 1 IC50 = 1.45 nM 8.84 Inhibition of PARP1 (unknown origin) using histone/NAD+ as substrates by NAD/NAD... 38776806
Poly [ADP-ribose] polymerase 1 IC50 = 1.479 nM 8.83 Inhibition of human full-length N-terminal GST-tagged PARP1 expressed in baculov... 31042381
Poly [ADP-ribose] polymerase 1 IC50 = 1.5 nM 8.82 Inhibition of human full-length N-terminal GST-tagged PARP1 expressed in baculov... 31042381
Poly [ADP-ribose] polymerase 1 Kd = 1.7 nM 8.77 Binding affinity to recombinant human HisGST-tagged PARP-1 catalytic domain by s... 26222319
Poly [ADP-ribose] polymerase 1 EC50 = 2.0 nM 8.7 Inhibition of PARP1 in human C41 cells after 30 mins by cell-based assay 19888760
Poly [ADP-ribose] polymerase 1 EC50 = 2.0 nM 8.7 Inhibition of PARP1 in human C41 cells 19143569
Poly [ADP-ribose] polymerase 1 Kd = 2.9 nM 8.54 Binding affinity to PARP1 (unknown origin) assessed as apparent dissociation con... 34570508
Poly [ADP-ribose] polymerase 2 Ki = 2.9 nM 8.54 Inhibition of PARP2 (unknown origin) assessed as inhibition constant 33650861
Poly [ADP-ribose] polymerase 2 IC50 = 2.9 nM 8.54 Inhibition of human PARP2 expressed in Escherichia coli using biotinylated histo... 31042381
Poly [ADP-ribose] polymerase 1 IC50 = 3.311 nM 8.48 Inhibition of full length recombinant human His6-tagged PARP1 expressed in Esche... 28001384
Poly [ADP-ribose] polymerase 1 Ki = 3.3 nM 8.48 Inhibition of PARP1 (unknown origin) 35051747
Poly [ADP-ribose] polymerase 1 IC50 = 3.3 nM 8.48 Inhibition of PARP1 (unknown origin) 37197461
Poly [ADP-ribose] polymerase 1 IC50 = 3.3 nM 8.48 Inhibition of full length recombinant human His6-tagged PARP1 expressed in Esche... 28001384
Poly [ADP-ribose] polymerase 1 IC50 = 4.73 nM 8.32 Inhibition of recombinant human PARP1 using HRP as substrate by ELISA analysis 38911148
Poly [ADP-ribose] polymerase 1 IC50 = 4.73 nM 8.32 Inhibition of human PARP1 using [3H]NAD as substrate after 1 min by microplate s... 26652717
Poly [ADP-ribose] polymerase 1 Ki = 5.0 nM 8.3 Inhibition of human recombinant PARP1 19143569

Literature References

PubMed DOI Target Context # Activities
19143569 10.1021/jm801171j MX1 8
24893124 10.1021/jm500415t Homo sapiens 7
19143569 10.1021/jm801171j Mus musculus 6
19143569 10.1021/jm801171j Rattus norvegicus 6
19143569 10.1021/jm801171j Canis familiaris 6
19143569 10.1021/jm801171j Cynomolgus monkey 6
37197461 10.1021/acsmedchemlett.3c00065 Poly [ADP-ribose] polymerase 1 6
28001384 10.1021/acs.jmedchem.6b00990 Poly [ADP-ribose] polymerase 1 6
19143569 10.1021/jm801171j B16-F10 5
19143569 10.1021/jm801171j Plasma 5
33691794 10.1186/s13148-021-01037-1 A549 5
23850199 10.1016/j.bmcl.2013.06.055 Poly [ADP-ribose] polymerase 1 4
27353531 10.1016/j.bmcl.2016.06.045 Poly [ADP-ribose] polymerase 1 4
27561983 10.1016/j.bmc.2016.08.016 Poly [ADP-ribose] polymerase 1 4
28001384 10.1021/acs.jmedchem.6b00990 Poly [ADP-ribose] polymerase 2 4
28001384 10.1021/acs.jmedchem.6b00990 Protein mono-ADP-ribosyltransferase PARP10 4
37484567 10.1039/d3md00117b Unchecked 4
34570508 10.1021/acs.jmedchem.1c01012 Poly [ADP-ribose] polymerase 1 3
31042381 10.1021/acs.jmedchem.8b01709 Poly [ADP-ribose] polymerase 1 3
24922587 10.1021/jm5002502 ADMET 3

Data from ChEMBL 36 via Core Engine