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Compound Detail

CHEMBL5395820

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C[C@@H](CN1CC(C(=O)N2CCN(c3ncc(C(F)(F)F)cn3)CC2)C1)Nc1cn[nH]c(=O)c1C(F)(F)F

Basic Information

ChEMBL ID CHEMBL5395820
Phase Preclinical
Structure Type MOL
InChI Key BMPSOKZAIFFMLK-LBPRGKRZSA-N
10
Targets
12
Activities
1
Assay Types
15
PK Parameters
14
Publications
0
Known Names

Molecular Properties

534.5
MW (Da)
1.68
ALogP
8
HBA
2
HBD
110.3
PSA (Ų)
0.54
QED
1
Ro5 Violations
6
Rot. Bonds

Drug Information

Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C21H24F6N8O2
MW 534.47
Aromatic Rings 2
Heavy Atoms 37
NP-Likeness -1.63

Activity Summary

IC50 12 meas. best 8.12

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Protein mono-ADP-ribosyltransferase TIPARP
CHEMBL2380188
IC50 8.12 8.12 7.6 2
Poly [ADP-ribose] polymerase tankyrase-1
CHEMBL6164
IC50 6.76 6.76 174.0 1
Poly [ADP-ribose] polymerase tankyrase-2
CHEMBL6154
IC50 6.64 6.64 227.0 1
Protein mono-ADP-ribosyltransferase PARP10
CHEMBL2429708
IC50 6.49 6.49 325.0 1
Protein mono-ADP-ribosyltransferase PARP12
CHEMBL2429709
IC50 6.34 6.34 453.0 1
Poly [ADP-ribose] polymerase 2
CHEMBL5366
IC50 6.26 6.26 546.0 1
NCI-H1373
CHEMBL4296389
IC50 5.96 5.96 1090.0 1
Protein mono-ADP-ribosyltransferase PARP14
CHEMBL2176777
IC50 5.66 5.66 2172.0 1
CT26
CHEMBL613866
IC50 4.89 4.8 12850.0 2
Protein mono-ADP-ribosyltransferase PARP11
CHEMBL2380189
IC50 4.49 4.49 32184.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 591.1 ng.hr.mL-1 Mus musculus
AUC 5663.5 ng.hr.mL-1 Mus musculus
CL 29.02 mL.min-1.kg-1 Mus musculus
CL 30.27 mL.min-1.kg-1 Mus musculus
Cmax 783205792654.41 nM Mus musculus
Cmax 4303328531068.16 nM Mus musculus
F 95.8 % Mus musculus
MRT 1.68 hr Mus musculus
MRT 1.97 hr Mus musculus
T1/2 1.44 hr Mus musculus
T1/2 1.74 hr Mus musculus
Tmax 0.08 hr Mus musculus
Tmax 0.58 hr Mus musculus
Vd 3.659 L.kg-1 Mus musculus
Vd 4.584 L.kg-1 Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 7.6 nM 8.12 Inhibition of human recombinant N-terminal FLAG tagged PARP7 (400 to 657 end res... 36576395
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 7.6 nM 8.12 Inhibition of human recombinant N-terminal FLAG-tagged PARP7 (400 to 657 end res... 36576395
Poly [ADP-ribose] polymerase tankyrase-1 IC50 = 174.0 nM 6.76 Inhibition of human recombinant N-terminal GST-tagged PARP5a (1001 to 1327 end r... 36576395
Poly [ADP-ribose] polymerase tankyrase-2 IC50 = 227.0 nM 6.64 Inhibition of human recombinant N-terminal GST-tagged PARP5b (667 to 1166 end re... 36576395
Protein mono-ADP-ribosyltransferase PARP10 IC50 = 325.0 nM 6.49 Inhibition of human recombinant N-terminal FLAG-tagged / C-terminal Strep-tagged... 36576395
Protein mono-ADP-ribosyltransferase PARP12 IC50 = 453.0 nM 6.34 Inhibition of human recombinant N-terminal GST-tagged PARP12 (500 to 701 end res... 36576395
Poly [ADP-ribose] polymerase 2 IC50 = 546.0 nM 6.26 Inhibition of human recombinant N-terminal GST-tagged PARP2 (2 to 583 residues) ... 36576395
NCI-H1373 IC50 = 1090.0 nM 5.96 Antiproliferative activity against human NCI-H1373 cells assessed as inhibition ... 36576395
Protein mono-ADP-ribosyltransferase PARP14 IC50 = 2172.0 nM 5.66 Inhibition of human recombinant N-terminal 6his-tagged / GST-tagged PARP14 (1470... 36576395
CT26 IC50 = 12850.0 nM 4.89 Antiproliferative activity against mouse CT26 cells assessed as inhibition of ce... 36576395
CT26 IC50 = 19470.0 nM 4.71 Antiproliferative activity against mouse CT26 cells assessed as inhibition of ce... 36576395
Protein mono-ADP-ribosyltransferase PARP11 IC50 = 32184.0 nM 4.49 Inhibition of human recombinant N-terminal GST-tagged / C-terminal His-tagged PA... 36576395

Literature References

PubMed DOI Target Context # Activities
36576395 10.1021/acs.jmedchem.2c01452 ADMET 22
36576395 10.1021/acs.jmedchem.2c01452 CT26 17
36576395 10.1021/acs.jmedchem.2c01452 Protein mono-ADP-ribosyltransferase TIPARP 6
36576395 10.1021/acs.jmedchem.2c01452 NCI-H1373 1
36576395 10.1021/acs.jmedchem.2c01452 Poly [ADP-ribose] polymerase 1 1
36576395 10.1021/acs.jmedchem.2c01452 Poly [ADP-ribose] polymerase 2 1
36576395 10.1021/acs.jmedchem.2c01452 Poly [ADP-ribose] polymerase tankyrase-1 1
36576395 10.1021/acs.jmedchem.2c01452 Poly [ADP-ribose] polymerase tankyrase-2 1
36576395 10.1021/acs.jmedchem.2c01452 Protein mono-ADP-ribosyltransferase PARP10 1
36576395 10.1021/acs.jmedchem.2c01452 Protein mono-ADP-ribosyltransferase PARP11 1
36576395 10.1021/acs.jmedchem.2c01452 Protein mono-ADP-ribosyltransferase PARP12 1
36576395 10.1021/acs.jmedchem.2c01452 Protein mono-ADP-ribosyltransferase PARP14 1
36576395 10.1021/acs.jmedchem.2c01452 AML12 1
36576395 10.1021/acs.jmedchem.2c01452 Voltage-gated inwardly rectifying potassium channel KCNH2 1

Data from ChEMBL 36 via Core Engine