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Compound Detail

CHEMBL5095043

ATAMPARIB
Phase I
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Phase I
C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F

Basic Information

ChEMBL ID CHEMBL5095043
Name ATAMPARIB
Phase Phase I
Structure Type MOL
InChI Key UQZCQKXJAXKZQH-LBPRGKRZSA-N

Known Names

Atamparib Rbn 2397 Rbn-2397 RBN2397
16
Targets
51
Activities
2
Assay Types
30
PK Parameters
20
Publications
4
Known Names
2
Indications

Molecular Properties

523.4
MW (Da)
2.15
ALogP
8
HBA
2
HBD
116.3
PSA (Ų)
0.40
QED
1
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Flags

Chemical Probe
USAN Stem -ampa-; -parib
USAN Year 2022

Extended Properties

Molecular Formula C20H23F6N7O3
MW 523.44
Aromatic Rings 2
Heavy Atoms 36
NP-Likeness -1.60

Indications

Carcinoma, Non-Small-Cell Lung Neoplasms

Activity Summary

IC50 49 meas. best 8.52
Kd 2 meas. best 9.66

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Protein mono-ADP-ribosyltransferase TIPARP
CHEMBL2380188
Kd 9.66 9.66 0.2 2
Protein mono-ADP-ribosyltransferase TIPARP
CHEMBL2380188
IC50 8.52 8.404 3.0 10
NCI-H1373
CHEMBL4296389
IC50 8.32 7.34 4.8 5
Poly [ADP-ribose] polymerase 2
CHEMBL5366
IC50 8.28 7.8533 5.3 6
Protein mono-ADP-ribosyltransferase PARP12
CHEMBL2429709
IC50 7.6 7.59 25.0 2
Poly [ADP-ribose] polymerase 1
CHEMBL3105
IC50 7.54 7.395 29.0 6
MV4-11
CHEMBL613835
IC50 6.29 5.695 510.0 2
U-937
CHEMBL612794
IC50 6.14 5.41 730.0 2
Protein mono-ADP-ribosyltransferase PARP3
CHEMBL5083
IC50 5.75 5.75 1800.0 1
Protein mono-ADP-ribosyltransferase PARP11
CHEMBL2380189
IC50 5.64 5.64 2281.0 2
Protein mono-ADP-ribosyltransferase PARP14
CHEMBL2176777
IC50 5.64 5.64 2300.0 1
CT26
CHEMBL613866
IC50 5.64 5.255 2310.0 4
Cytochrome P450 2C9
CHEMBL3397
IC50 5.5 5.5 3130.0 1
Poly [ADP-ribose] polymerase tankyrase-2
CHEMBL6154
IC50 5.46 5.3775 3446.0 4
Unchecked
CHEMBL612545
IC50 5.34 5.34 4540.0 1
Protein mono-ADP-ribosyltransferase PARP4
CHEMBL6142
IC50 5.04 5.04 9200.0 1
Protein mono-ADP-ribosyltransferase PARP16
CHEMBL4105981
IC50 4.6 4.6 25000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 256.0 ng.hr.mL-1 Mus musculus
AUC 656.0 ng.hr.mL-1 Mus musculus
AUC 470.0 ng.hr.mL-1 Mus musculus
AUC 617.0 ng.hr.mL-1 Mus musculus
AUC 4694.0 ng.hr.mL-1 Canis lupus familiaris
AUC 5508.0 ng.hr.mL-1 Canis lupus familiaris
CL 67.05 mL.min-1.kg-1 Mus musculus
CL 259.29 mL.min-1.kg-1 Mus musculus
CL 67.05 mL.min-1.kg-1 Mus musculus
CL 72.6 mL.min-1.kg-1 Mus musculus
CL 16.2 mL.min-1.kg-1 Canis lupus familiaris
CL 23.2 mL.min-1.kg-1 Homo sapiens
CL 94.8 mL.min-1.kg-1 Macaca mulatta
CL 17.1 mL.min-1.kg-1 Canis lupus familiaris
CL 110.0 mL.min-1.kg-1 Rattus norvegicus
CL 345.0 mL.min-1.kg-1 Mus musculus
Cmax 1446202047990.22 nM Mus musculus
Cmax 2495605991135.56 nM Mus musculus
Cmax 1900886.44 nM Mus musculus
Cmax 3433058.23 nM Canis lupus familiaris
F 25.67 % Mus musculus
F 25.67 % Mus musculus
F 26.2 % Mus musculus
F 23.4 % Canis lupus familiaris
MRT 0.2 hr Mus musculus
MRT 0.9 hr Mus musculus
T1/2 0.15 hr Mus musculus
T1/2 0.9 hr Mus musculus
T1/2 0.2 hr Mus musculus
T1/2 2.7 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Protein mono-ADP-ribosyltransferase TIPARP Kd = 0.22 nM 9.66 Binding affinity to PARP7 (unknown origin) assessed as dissociation constant 37826932
Protein mono-ADP-ribosyltransferase TIPARP Kd = 0.22 nM 9.66 Binding affinity to PARP7 (unknown origin) assessed as dissociation constant 35608571
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 3.0 nM 8.52 Displacement of fluorescent labeled RBN011198 from human NanoLuc-tagged full-len... 35500474
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 3.0 nM 8.52 Inhibition of PARP7 (unknown origin) by probe displacement assay 38059836
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 3.0 nM 8.52 Inhibition of PARP7 (unknown origin) 37843892
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 3.1 nM 8.51 Inhibition of PARP7 (unknown origin) incubated for 1 hr by chemiluminescence bas... 38277917
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 3.1 nM 8.51 Inhibition of N-terminal FLAG tagged human PARP7 (400 to 657 residues) preincuba... 38456618
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 3.06 nM 8.51 Inhibition of PARP7 (unknown origin) using histone as substrate incubated for 1 ... 37826932
NCI-H1373 IC50 = 4.76 nM 8.32 Antiproliferative activity against human NCI-H1373 cells assessed as inhibition ... 36576395
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 5.0 nM 8.3 Inhibition of human recombinant N-terminal FLAG tagged PARP7 (400 to 657 end res... 36576395
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 5.0 nM 8.3 Inhibition of human recombinant N-terminal FLAG-tagged PARP7 (400 to 657 end res... 36576395
Poly [ADP-ribose] polymerase 2 IC50 = 5.3 nM 8.28 Inhibition of N-terminal GST tagged human PARP2 (2 to 583 residues) infected in ... 38456618
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 5.6 nM 8.25 Inhibition of PARP7 (unknown origin) measured after 1 hr incubation by microplat... 38059836
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 8.0 nM 8.1 Inhibition of human recombinant N-terminal FLAG-tagged PARP7 (400 to 657(end) re... 37843892
Poly [ADP-ribose] polymerase 2 IC50 = 17.0 nM 7.77 Inhibition of PARP2 (unknown origin) by probe displacement assay 38059836
Poly [ADP-ribose] polymerase 2 IC50 = 17.0 nM 7.77 Inhibition of PARP2 (unknown origin) 35608571
Poly [ADP-ribose] polymerase 2 IC50 = 17.0 nM 7.77 Inhibition of human recombinant N-terminal GST-tagged PARP2 (2 to 583 residues) ... 36576395
Poly [ADP-ribose] polymerase 2 IC50 = 17.0 nM 7.77 Inhibition of PARP2 (unknown origin) 38456618
Poly [ADP-ribose] polymerase 2 IC50 = 17.4 nM 7.76 Inhibition of PARP2 (unknown origin) 38277917
Protein mono-ADP-ribosyltransferase PARP12 IC50 = 25.0 nM 7.6 Inhibition of PARP12 (unknown origin) by probe displacement assay 38059836

Literature References

PubMed DOI Target Context # Activities
37826932 10.1016/j.ejmech.2023.115836 ADMET 34
36576395 10.1021/acs.jmedchem.2c01452 ADMET 20
- 10.6019/CHEMBL5303304 Fibroblast 8
37826932 10.1016/j.ejmech.2023.115836 No relevant target 6
- 10.6019/CHEMBL5303304 HEK-293T 6
38059836 10.1021/acs.jmedchem.3c01764 ADMET 5
36576395 10.1021/acs.jmedchem.2c01452 CT26 5
38059836 10.1021/acs.jmedchem.3c01764 CT26 4
38456618 10.1021/acs.jmedchem.4c00090 NCI-H1373 4
38456618 10.1021/acs.jmedchem.4c00090 MV4-11 4
37826932 10.1016/j.ejmech.2023.115836 Protein mono-ADP-ribosyltransferase TIPARP 3
38456618 10.1021/acs.jmedchem.4c00090 Unchecked 3
38059836 10.1021/acs.jmedchem.3c01764 Protein mono-ADP-ribosyltransferase TIPARP 3
38456618 10.1021/acs.jmedchem.4c00090 Poly [ADP-ribose] polymerase 2 2
35608571 10.1021/acs.jmedchem.2c00281 Protein mono-ADP-ribosyltransferase TIPARP 2
38059836 10.1021/acs.jmedchem.3c01764 Poly [ADP-ribose] polymerase 1 2
38456618 10.1021/acs.jmedchem.4c00090 Poly [ADP-ribose] polymerase tankyrase-1 2
38456618 10.1021/acs.jmedchem.4c00090 U-937 2
38456618 10.1021/acs.jmedchem.4c00090 Poly [ADP-ribose] polymerase tankyrase-2 2
38456618 10.1021/acs.jmedchem.4c00090 Signal transducer and activator of transcription 1-alpha/beta 2

Data from ChEMBL 36 via Core Engine