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Compound Detail

CHEMBL4086276

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Cc1cc2c(cc1N1C(=O)c3cccc4c(CCCO)ccc(c34)C1=O)n(C)c(=O)n2C

Basic Information

ChEMBL ID CHEMBL4086276
Phase Preclinical
Structure Type MOL
InChI Key OFWWWKWUCDUISA-UHFFFAOYSA-N
8
Targets
48
Activities
3
Assay Types
13
PK Parameters
20
Publications
0
Known Names

Molecular Properties

429.5
MW (Da)
3.06
ALogP
6
HBA
1
HBD
84.5
PSA (Ų)
0.51
QED
0
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula C25H23N3O4
MW 429.48
Aromatic Rings 4
Heavy Atoms 32
NP-Likeness -0.54

Activity Summary

IC50 36 meas. best 8.22
Kd 11 meas. best 8.03
EC50 1 meas. best 7.16

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Bromodomain-containing protein 1
CHEMBL2176774
IC50 8.22 6.9907 6.0 14
Transcription initiation factor TFIID subunit 1
CHEMBL3217390
IC50 8.1 7.335 8.0 10
Transcription initiation factor TFIID subunit 1
CHEMBL3217390
Kd 8.03 6.832 9.3 5
Bromodomain-containing protein 1
CHEMBL2176774
Kd 7.44 7.4067 36.0 3
Transcription initiation factor TFIID subunit 1
CHEMBL3217390
EC50 7.16 7.16 70.0 1
Transcription initiation factor TFIID subunit 1-like
CHEMBL3108641
IC50 6.97 6.97 106.0 2
Transcription initiation factor TFIID subunit 1-like
CHEMBL3108641
Kd 6.63 6.63 234.7 1
Chromatin remodeling regulator CECR2
CHEMBL3108639
Kd 5.86 5.86 1390.0 1
CREB-binding protein
CHEMBL5747
Kd 5.86 5.86 1390.0 1
CREB-binding protein
CHEMBL5747
IC50 5.77 5.77 1710.0 1
Peregrin
CHEMBL3132741
IC50 5.64 5.426 2280.0 5
Bromodomain and PHD finger-containing protein 3
CHEMBL3108644
IC50 5.61 5.3767 2450.0 3
MDA-MB-231
CHEMBL400
IC50 4.32 4.32 48000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 1000.0 ng.hr.mL-1 Rattus norvegicus
AUC 1500.0 ng.hr.mL-1 Rattus norvegicus
CL 3.167 mL.min-1.kg-1 Mus musculus
CL 2.5 mL.min-1.kg-1 Rattus norvegicus
CL 0.01667 mL.min-1.kg-1 Canis lupus familiaris
CL 0.01667 mL.min-1.kg-1 Homo sapiens
CL 63.33 mL.min-1.kg-1 Rattus norvegicus
CL 25.0 mL.min-1.kg-1 Canis lupus familiaris
CL 12.17 mL.min-1.kg-1 Rattus norvegicus
F 73.0 % Rattus norvegicus
Fu 0.0058 - Mus musculus
Fu 0.043 - Homo sapiens
T1/2 10.0 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Bromodomain-containing protein 1 IC50 = 6.0 nM 8.22 Inhibition of recombinant human BRD1 (E556 to A688 residues) expressed in bacter... 27935314
Bromodomain-containing protein 1 IC50 = 6.0 nM 8.22 Selectivity interaction (Enzyme activity assay (BROMOscan®)) EUB0000191c BRD1 -
Transcription initiation factor TFIID subunit 1 IC50 = 8.0 nM 8.1 Inhibition of human GST-tagged TAF1 BD2 (1519 to 1651 residues) expressed in Esc... 28402630
Transcription initiation factor TFIID subunit 1 IC50 = 8.0 nM 8.1 Affinity Biochemical interaction (TR-FRET assay) EUB0000191c TAF1 -
Transcription initiation factor TFIID subunit 1 Kd = 9.3 nM 8.03 Binding affinity to human TAF1 tandem bromodomain (1373 to 1499 residues) transf... 35191694
Transcription initiation factor TFIID subunit 1 IC50 = 11.0 nM 7.96 Inhibition of human GST-tagged TAF1 BD2 (1519 to 1651 residues) expressed in Esc... 28402630
Transcription initiation factor TFIID subunit 1 IC50 = 13.0 nM 7.89 Inhibition of recombinant human TAF1 (D1521 to D1656 residues) expressed in bact... 27935314
Transcription initiation factor TFIID subunit 1 IC50 = 13.0 nM 7.89 Selectivity interaction (Enzyme activity assay (BROMOscan®)) EUB0000191c TAF1 -
Transcription initiation factor TFIID subunit 1 Kd = 16.61 nM 7.78 Binding affinity to human GST-tagged TAF1 BD2 (1519 to 1651 residues) expressed ... 28402630
Transcription initiation factor TFIID subunit 1 IC50 = 17.0 nM 7.77 Inhibition of human GST-tagged TAF1 BD2 (1519 to 1651 residues) expressed in Esc... 28402630
Transcription initiation factor TFIID subunit 1 IC50 = 17.0 nM 7.77 Selectivity interaction (ITC) EUB0000191c TAF1 -
Bromodomain-containing protein 1 Kd = 36.0 nM 7.44 Binding affinity to human BRPF2 BD (563 to 688 residues) expressed in Escherichi... 28402630
Bromodomain-containing protein 1 Kd = 37.0 nM 7.43 Binding affinity to human BRPF2 BD (563 to 688 residues) expressed in Escherichi... 28402630
Bromodomain-containing protein 1 IC50 = 45.0 nM 7.35 Selectivity interaction (ITC) EUB0000191c BRD1 -
Bromodomain-containing protein 1 Kd = 44.64 nM 7.35 Binding affinity to human BRPF2 BD (563 to 688 residues) expressed in Escherichi... 28402630
Transcription initiation factor TFIID subunit 1 Kd = 46.7 nM 7.33 Binding affinity to human TAF1 BD 2 (1501 to 1635 residues) transfected in Esche... 35191694
Bromodomain-containing protein 1 IC50 = 62.0 nM 7.21 Inhibition of human BRPF2 (563 to 688 residues) expressed in Escherichia coli BL... 28402630
Bromodomain-containing protein 1 IC50 = 67.0 nM 7.17 Affinity Biochemical interaction (TR-FRET assay) EUB0000191c BRD1 -
Bromodomain-containing protein 1 IC50 = 67.0 nM 7.17 Inhibition of human BRPF2 (563 to 688 residues) expressed in Escherichia coli BL... 28402630
Transcription initiation factor TFIID subunit 1 EC50 = 70.0 nM 7.16 Binding affinity to TAF1 in HEK293T cells assessed as increase in TAF1 level by ... 35191694

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL4689842 U2OS 346
- 10.6019/CHEMBL4689842 Fibroblast 345
- 10.6019/CHEMBL4689842 HEK-293T 340
27935314 10.1021/acs.jmedchem.6b00923 ADMET 17
28402630 10.1021/acs.jmedchem.7b00306 Bromodomain-containing protein 1 15
28402630 10.1021/acs.jmedchem.7b00306 ADMET 13
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
28402630 10.1021/acs.jmedchem.7b00306 Transcription initiation factor TFIID subunit 1 11
27935314 10.1021/acs.jmedchem.6b00923 No relevant target 9
28402630 10.1021/acs.jmedchem.7b00306 Liver 8
35191694 10.1021/acs.jmedchem.1c01999 Unchecked 8
28402630 10.1021/acs.jmedchem.7b00306 Bromodomain-containing protein 4 7
28402630 10.1021/acs.jmedchem.7b00306 Unchecked 7
28402630 10.1021/acs.jmedchem.7b00306 Peregrin 7
28402630 10.1021/acs.jmedchem.7b00306 Rattus norvegicus 6
28402630 10.1021/acs.jmedchem.7b00306 No relevant target 6
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
35191694 10.1021/acs.jmedchem.1c01999 Transcription initiation factor TFIID subunit 1 6
28402630 10.1021/acs.jmedchem.7b00306 Protein polybromo-1 6

Data from ChEMBL 36 via Core Engine