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Compound Detail

CHEMBL5558410

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COc1ccc(Cl)cc1-c1cc(C)ncc1C(=O)Nc1nnc(OCC2CCN(C(=O)c3cc(Cc4n[nH]c(=O)c5ccccc45)ccc3F)CC2)s1

Basic Information

ChEMBL ID CHEMBL5558410
Phase Preclinical
Structure Type MOL
InChI Key BWTOWBOMDHKCDB-UHFFFAOYSA-N
14
Targets
15
Activities
1
Assay Types
16
PK Parameters
18
Publications
0
Known Names

Molecular Properties

754.2
MW (Da)
6.72
ALogP
10
HBA
2
HBD
152.3
PSA (Ų)
0.16
QED
2
Ro5 Violations
10
Rot. Bonds

Drug Information

Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C38H33ClFN7O5S
MW 754.24
Aromatic Rings 6
Heavy Atoms 53
NP-Likeness -1.59

Activity Summary

IC50 15 meas. best 8.64

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Poly [ADP-ribose] polymerase 2
CHEMBL5366
IC50 8.64 8.64 2.3 1
Poly [ADP-ribose] polymerase 1
CHEMBL3105
IC50 8.27 8.27 5.4 1
DNA polymerase theta
CHEMBL6025
IC50 7.34 7.2 45.6 2
Protein mono-ADP-ribosyltransferase PARP3
CHEMBL5083
IC50 7.29 7.29 51.2 1
Poly [ADP-ribose] polymerase tankyrase-2
CHEMBL6154
IC50 6.81 6.81 156.0 1
Protein mono-ADP-ribosyltransferase TIPARP
CHEMBL2380188
IC50 6.71 6.71 194.0 1
Poly [ADP-ribose] polymerase tankyrase-1
CHEMBL6164
IC50 6.69 6.69 206.0 1
Protein mono-ADP-ribosyltransferase PARP10
CHEMBL2429708
IC50 5.96 5.96 1103.0 1
MDA-MB-436
CHEMBL4296465
IC50 5.57 5.57 2700.0 1
SW48
CHEMBL614055
IC50 5.54 5.54 2900.0 1
Protein mono-ADP-ribosyltransferase PARP8
CHEMBL3091262
IC50 5.53 5.53 2934.0 1
HCT-116
CHEMBL394
IC50 5.05 5.05 8900.0 1
SK-OV-3
CHEMBL614925
IC50 4.72 4.72 18900.0 1
HCC1937
CHEMBL1075458
IC50 4.68 4.68 20900.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 723.8 ng.hr.mL-1 Rattus norvegicus
AUC 738.0 ng.hr.mL-1 Rattus norvegicus
CL 681.02 mL.min-1.kg-1 Homo sapiens
CL 802.0 mL.min-1.kg-1 Rattus norvegicus
CL 1069.93 mL.min-1.kg-1 Mus musculus
CL 22.67 mL.min-1.kg-1 Rattus norvegicus
Cmax 1.945 ug.mL-1 Rattus norvegicus
MRT 0.6 hr Rattus norvegicus
T1/2 0.03917 hr Homo sapiens
T1/2 0.05183 hr Rattus norvegicus
T1/2 0.085 hr Mus musculus
T1/2 2.0 hr Rattus norvegicus
T1/2 38.5 hr Rattus norvegicus
T1/2 38.5 hr Mus musculus
Tmax 0.08 hr Rattus norvegicus
Vd 3.973 L.kg-1 Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Poly [ADP-ribose] polymerase 2 IC50 = 2.3 nM 8.64 Inhibition of PARP2 (unknown origin) 38375763
Poly [ADP-ribose] polymerase 1 IC50 = 5.4 nM 8.27 Inhibition of human PARP1 incubated for 90 mins by colorimetric assay 38375763
DNA polymerase theta IC50 = 45.6 nM 7.34 Inhibition of DNA polymerase theta (unknown origin) ATPase activity incubated fo... 38375763
Protein mono-ADP-ribosyltransferase PARP3 IC50 = 51.2 nM 7.29 Inhibition of PARP3 (unknown origin) 38375763
DNA polymerase theta IC50 = 88.0 nM 7.06 Inhibition of DNA polymerase theta mediated TMEJ repair activity in HEK293 cells... 38375763
Poly [ADP-ribose] polymerase tankyrase-2 IC50 = 156.0 nM 6.81 Inhibition of PARP5b (unknown origin) 38375763
Protein mono-ADP-ribosyltransferase TIPARP IC50 = 194.0 nM 6.71 Inhibition of PARP7 (unknown origin) 38375763
Poly [ADP-ribose] polymerase tankyrase-1 IC50 = 206.0 nM 6.69 Inhibition of PARP5a (unknown origin) 38375763
Protein mono-ADP-ribosyltransferase PARP10 IC50 = 1103.0 nM 5.96 Inhibition of PARP10 (unknown origin) 38375763
MDA-MB-436 IC50 = 2700.0 nM 5.57 Antiproliferative activity against BRCA1-deficient human MDA-MB-436 cells assess... 38375763
SW48 IC50 = 2900.0 nM 5.54 Antiproliferative activity against BRCA2-deficient human SW48 cells assessed as ... 38375763
Protein mono-ADP-ribosyltransferase PARP8 IC50 = 2934.0 nM 5.53 Inhibition of PARP8 (unknown origin) 38375763
HCT-116 IC50 = 8900.0 nM 5.05 Antiproliferative activity against BRCA2-deficient human HCT-116 cells assessed ... 38375763
SK-OV-3 IC50 = 18900.0 nM 4.72 Antiproliferative activity against BRCA-proficient human SK-OV-3 cells assessed ... 38375763
HCC1937 IC50 = 20900.0 nM 4.68 Antiproliferative activity against BRCA1-deficient human HCC1937 cells assessed ... 38375763

Literature References

PubMed DOI Target Context # Activities
38375763 10.1021/acs.jmedchem.3c02096 ADMET 23
38375763 10.1021/acs.jmedchem.3c02096 MDA-MB-231 10
38375763 10.1021/acs.jmedchem.3c02096 MDA-MB-436 3
38375763 10.1021/acs.jmedchem.3c02096 Poly [ADP-ribose] polymerase 1 2
38375763 10.1021/acs.jmedchem.3c02096 Unchecked 2
38375763 10.1021/acs.jmedchem.3c02096 DNA polymerase theta 2
38375763 10.1021/acs.jmedchem.3c02096 HCC1937 1
38375763 10.1021/acs.jmedchem.3c02096 HCT-116 1
38375763 10.1021/acs.jmedchem.3c02096 SW48 1
38375763 10.1021/acs.jmedchem.3c02096 SK-OV-3 1
38375763 10.1021/acs.jmedchem.3c02096 MCF-10A 1
38375763 10.1021/acs.jmedchem.3c02096 Poly [ADP-ribose] polymerase 2 1
38375763 10.1021/acs.jmedchem.3c02096 Protein mono-ADP-ribosyltransferase PARP3 1
38375763 10.1021/acs.jmedchem.3c02096 Poly [ADP-ribose] polymerase tankyrase-1 1
38375763 10.1021/acs.jmedchem.3c02096 Poly [ADP-ribose] polymerase tankyrase-2 1
38375763 10.1021/acs.jmedchem.3c02096 Protein mono-ADP-ribosyltransferase TIPARP 1
38375763 10.1021/acs.jmedchem.3c02096 Protein mono-ADP-ribosyltransferase PARP8 1
38375763 10.1021/acs.jmedchem.3c02096 Protein mono-ADP-ribosyltransferase PARP10 1

Data from ChEMBL 36 via Core Engine