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Compound Detail

CHEMBL2177300

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CC(=O)N1c2ccc(-c3ccc(C(=O)O)cc3)cc2[C@H](Nc2ccc(Cl)cc2)C[C@@H]1C

Basic Information

ChEMBL ID CHEMBL2177300
Phase Preclinical
Structure Type MOL
InChI Key FAWSUKOIROHXAP-NPMXOYFQSA-N
21
Targets
53
Activities
3
Assay Types
24
PK Parameters
20
Publications
0
Known Names

Molecular Properties

434.9
MW (Da)
6.00
ALogP
3
HBA
2
HBD
69.6
PSA (Ų)
0.53
QED
1
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C25H23ClN2O3
MW 434.92
Aromatic Rings 3
Heavy Atoms 31
NP-Likeness -0.58

Activity Summary

IC50 36 meas. best 9.6
Kd 12 meas. best 8.36
EC50 5 meas. best 6.98

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Bromodomain-containing protein 3
CHEMBL1795186
IC50 9.6 8.12 0.3 5
Bromodomain-containing protein 4
CHEMBL1163125
IC50 9.4 7.9825 0.4 8
Bromodomain-containing protein 2
CHEMBL1293289
IC50 8.5 7.072 3.2 5
Bromodomain-containing protein 4
CHEMBL1163125
Kd 8.36 8.042 4.4 5
Bromodomain-containing protein 3
CHEMBL1795186
Kd 7.7 7.7 20.0 1
Bromodomain-containing protein 2
CHEMBL1293289
Kd 7.6 7.6 25.0 1
Bromodomain testis-specific protein
CHEMBL1795185
IC50 7.3 5.4333 50.1 3
PBMC
CHEMBL613107
IC50 7.3 7.3 50.1 1
MV4-11
CHEMBL613835
EC50 6.98 6.98 104.7 1
Unchecked
CHEMBL612545
EC50 6.7 6.605 200.0 2
HL-60
CHEMBL383
EC50 6.69 6.69 204.2 1
Whole blood
CHEMBL2367389
IC50 6.4 6.4 398.1 1
Protein polybromo-1
CHEMBL1795184
IC50 6.2 6.2 631.0 1
LOUCY
CHEMBL2366252
EC50 6.16 6.16 700.0 1
Unchecked
CHEMBL612545
Kd 5.82 5.7625 1520.0 4
CREB-binding protein
CHEMBL5747
Kd 5.2 5.2 6300.0 1
Transcription intermediary factor 1-alpha
CHEMBL3108638
IC50 5.0 4.9 10000.0 2
Cytochrome P450 2C19
CHEMBL3622
IC50 4.92 4.92 12000.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 4.89 4.89 13000.0 1
E3 ubiquitin-protein ligase TRIM33
CHEMBL2176772
IC50 4.8 4.8 15848.9 1
Cytochrome P450 3A4
CHEMBL340
IC50 4.68 4.59 21000.0 2
Transcription initiation factor TFIID subunit 1
CHEMBL3217390
IC50 4.5 4.5 31622.8 1
Bromodomain and WD repeat-containing protein 1
CHEMBL3351192
IC50 4.5 4.5 31622.8 1
Histone acetyltransferase p300
CHEMBL3784
IC50 4.5 4.5 31622.8 1
Transcription initiation factor TFIID subunit 1-like
CHEMBL3108641
IC50 4.5 4.5 31622.8 1
CREB-binding protein
CHEMBL5747
IC50 4.5 4.5 31622.8 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 6028.0 ng.hr.mL-1 Mus musculus
AUC 539.0 ng.hr.mL-1 Rattus norvegicus
AUC 5900.0 ng.hr.mL-1 Canis lupus familiaris
AUC 10968.0 ng.hr.mL-1 Macaca fascicularis
CL 3.1 mL.min-1.kg-1 Mus musculus
CL 26.0 mL.min-1.kg-1 Rattus norvegicus
CL 6.0 mL.min-1.kg-1 Canis lupus familiaris
CL 3.0 mL.min-1.kg-1 Macaca fascicularis
F 45.0 % Mus musculus
F 28.0 % Rattus norvegicus
F 80.0 % Canis lupus familiaris
F 103.0 % Macaca fascicularis
F 80.0 % Canis lupus familiaris
F 100.0 % Macaca mulatta
Fu 0.013 - Mus musculus
Fu 0.009 - Rattus norvegicus
Fu 0.065 - Canis lupus familiaris
Fu 0.017 - Homo sapiens
T1/2 3.6 hr Mus musculus
T1/2 8.0 hr Rattus norvegicus
T1/2 1.8 hr Canis lupus familiaris
T1/2 2.7 hr Macaca fascicularis
T1/2 1.8 hr Canis lupus familiaris
T1/2 2.7 hr Macaca mulatta

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Bromodomain-containing protein 3 IC50 = 0.2512 nM 9.6 Binding affinity to full-length BRD4 short isoform (unknown origin) by BROMOscan... 25249180
Bromodomain-containing protein 4 IC50 = 0.3981 nM 9.4 Inhibition of human BRD4 bromodomain 1 by BROMOscan assay 25249180
Bromodomain-containing protein 4 IC50 = 0.3981 nM 9.4 Inhibition of human BRD4 bromodomain 1/2 by BROMOscan assay 25249180
Bromodomain-containing protein 3 IC50 = 0.631 nM 9.2 Inhibition of human BRD3 bromodomain 1 by BROMOscan assay 25249180
Bromodomain-containing protein 3 IC50 = 1.995 nM 8.7 Inhibition of human BRD3 bromodomain 2 by BROMOscan assay 25249180
Bromodomain-containing protein 4 IC50 = 3.162 nM 8.5 Inhibition of human BRD4 bromodomain 2 by BROMOscan assay 25249180
Bromodomain-containing protein 2 IC50 = 3.162 nM 8.5 Inhibition of human BRD2 bromodomain 2 by BROMOscan assay 25249180
Bromodomain-containing protein 4 Kd = 4.4 nM 8.36 Binding affinity to His6-tagged BRD4 (1 to 477 aa) (unknown origin) by ITC metho... 25249180
Bromodomain-containing protein 4 Kd = 4.4 nM 8.36 Binding affinity to BRD4 (unknown origin) by isothermal titration calorimetry 30542529
Bromodomain-containing protein 4 Kd = 6.23 nM 8.21 Binding affinity to human BRD4 BD 1 assessed as dissociation constant by ITC ana... 38048437
Bromodomain-containing protein 4 IC50 = 6.31 nM 8.2 Displacement of (+)-JQ1 from 6H-Thr BRD4 Y97A mutant BD2 (unknown origin) after ... 29656650
Bromodomain-containing protein 4 IC50 = 15.85 nM 7.8 Displacement of (+)-JQ1 from 6H-Thr BRD4 Y390A mutant BD1 (unknown origin) after... 29656650
Bromodomain-containing protein 3 Kd = 20.0 nM 7.7 Binding affinity to His6-tagged BRD3 (1 to 475 aa) (unknown origin) by SPR metho... 25249180
Bromodomain-containing protein 4 IC50 = 22.0 nM 7.66 Inhibition of BRD4 (unknown origin) 28765013
Bromodomain-containing protein 4 Kd = 23.0 nM 7.64 Binding affinity to His6-tagged BRD4 (1 to 477 aa) (unknown origin) by SPR metho... 25249180
Bromodomain-containing protein 4 Kd = 23.0 nM 7.64 Binding affinity to BRD4 (unknown origin) by surface plasmon resonance analysis 30542529
Bromodomain-containing protein 2 Kd = 25.0 nM 7.6 Binding affinity to His6-tagged BRD2 (1 to 473 aa) (unknown origin) by SPR metho... 25249180
Bromodomain-containing protein 2 IC50 = 30.0 nM 7.52 Inhibition of recombinant human BRD2 bromodomain 2 (342 to 460 residues) using b... 29170024
Bromodomain testis-specific protein IC50 = 50.12 nM 7.3 Inhibition of BRDT (unknown origin) by TR-FRET assay 25249180
PBMC IC50 = 50.12 nM 7.3 Inhibition of LPS-induced IL6 production in human PBMC after 18 to 24 hrs by imm... 25249180

Literature References

PubMed DOI Target Context # Activities
25249180 10.1021/jm5010539 Mus musculus 8
25249180 10.1021/jm5010539 Bromodomain-containing protein 4 7
25249180 10.1021/jm5010539 Bromodomain-containing protein 3 6
38048437 10.1021/acs.jmedchem.3c01321 Unchecked 6
25249180 10.1021/jm5010539 Bromodomain-containing protein 2 5
25249180 10.1021/jm5010539 Rattus norvegicus 5
25249180 10.1021/jm5010539 Cynomolgus monkey 5
25249180 10.1021/jm5010539 Canis familiaris 5
25249180 10.1021/jm5010539 ADMET 4
28595007 10.1021/acs.jmedchem.6b01912 von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 4 4
30542529 10.1039/C8MD00198G ADMET 4
33691794 10.1186/s13148-021-01037-1 A549 4
25249180 10.1021/jm5010539 Molecular identity unknown 4
25249180 10.1021/jm5010539 Bromodomain testis-specific protein 3
25249180 10.1021/jm5010539 Cytochrome P450 3A4 3
29656650 10.1021/acs.jmedchem.7b01666 Bromodomain-containing protein 4 3
29170024 10.1016/j.bmc.2017.10.042 Unchecked 3
25249180 10.1021/jm5010539 CREB-binding protein 2
29170024 10.1016/j.bmc.2017.10.042 Bromodomain-containing protein 2 2
25249180 10.1021/jm5010539 Protein polybromo-1 2

Data from ChEMBL 36 via Core Engine