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Compound Detail

CHEMBL4297454

ABBV-744
Phase I
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Phase I
CCNC(=O)c1cc2c(-c3cc(C(C)(C)O)ccc3Oc3c(C)cc(F)cc3C)cn(C)c(=O)c2[nH]1

Basic Information

ChEMBL ID CHEMBL4297454
Name ABBV-744
Phase Phase I
Structure Type MOL
InChI Key OEDSFMUSNZDJFD-UHFFFAOYSA-N

Known Names

Abbv-744
10
Targets
49
Activities
3
Assay Types
30
PK Parameters
20
Publications
1
Known Names
2
Indications

Molecular Properties

491.6
MW (Da)
5.06
ALogP
5
HBA
3
HBD
96.3
PSA (Ų)
0.35
QED
1
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Flags

Chemical Probe

Extended Properties

Molecular Formula C28H30FN3O4
MW 491.56
Aromatic Rings 4
Heavy Atoms 36
NP-Likeness -0.45

Indications

Leukemia, Myeloid, Acute Primary Myelofibrosis

Activity Summary

IC50 29 meas. best 9.19
Ki 16 meas. best 9.0
Kd 4 meas. best 8.8

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Bromodomain-containing protein 4
CHEMBL1163125
IC50 9.19 7.45 0.7 11
Bromodomain-containing protein 2
CHEMBL1293289
IC50 9.1 7.788 0.8 5
Bromodomain-containing protein 3
CHEMBL1795186
IC50 9.06 8.0233 0.9 3
Bromodomain testis-specific protein
CHEMBL1795185
Ki 9.0 7.52 1.0 2
Bromodomain-containing protein 4
CHEMBL1163125
Ki 8.85 7.53 1.4 10
Bromodomain-containing protein 4
CHEMBL1163125
Kd 8.8 7.31 1.6 4
Bromodomain-containing protein 2
CHEMBL1293289
Ki 8.34 7.135 4.6 2
Bromodomain-containing protein 3
CHEMBL1795186
Ki 8.31 6.905 4.9 2
SKM-1
CHEMBL2366085
IC50 8.17 8.17 6.7 1
MV4-11
CHEMBL613835
IC50 7.82 7.16 15.0 4
MOLM-13
CHEMBL3706572
IC50 7.41 7.41 39.0 1
Unchecked
CHEMBL612545
IC50 6.4 6.4 398.1 1
NCI-H1299
CHEMBL612255
IC50 5.8 5.8 1600.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.55 5.53 2800.0 2

Pharmacokinetic Data

Parameter Value Units Species
AUC 293.2 - Chlorocebus sabaeus
AUC 200.0 ng.hr.mL-1 Macaca mulatta
AUC 3800.0 ng.hr.mL-1 Mus musculus
AUC 500.0 ng.hr.mL-1 Rattus norvegicus
AUC 460.0 ng.hr.mL-1 Canis lupus familiaris
AUC 2350.0 ng.hr.mL-1 Mus musculus
AUC 120.0 ng.hr.mL-1 Rattus norvegicus
AUC 1050.0 ng.hr.mL-1 Canis lupus familiaris
AUC 14.0 ng.hr.mL-1 Macaca mulatta
CL 143.33 mL.min-1.kg-1 Homo sapiens
CL 750.0 mL.min-1.kg-1 Mus musculus
CL 200.0 mL.min-1.kg-1 Rattus norvegicus
CL 25.67 mL.min-1.kg-1 Macaca mulatta
CL 4.833 mL.min-1.kg-1 Mus musculus
CL 11.17 mL.min-1.kg-1 Rattus norvegicus
CL 4.0 mL.min-1.kg-1 Canis lupus familiaris
CL - - Rattus norvegicus
Cmax 427.21 nM Mus musculus
Cmax 24.41 nM Rattus norvegicus
Cmax 235.98 nM Canis lupus familiaris
Cmax 10.17 nM Macaca mulatta
F 58.0 % Mus musculus
F 24.0 % Rattus norvegicus
F 77.0 % Canis lupus familiaris
F 7.0 % Macaca mulatta
F 24.0 % Rattus norvegicus
T1/2 2.0 hr Macaca mulatta
T1/2 3.0 hr Mus musculus
T1/2 2.9 hr Rattus norvegicus
T1/2 4.4 hr Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Bromodomain-containing protein 4 IC50 = 0.65 nM 9.19 Inhibition of C-terminal His6-tagged BRD4 BD2 (unknown origin) using H-YSGRGK(Ac... 35333526
Bromodomain-containing protein 2 IC50 = 0.8 nM 9.1 Inhibition of BRD2 BD2 (unknown origin) using biotinylated tetra-acetylated H4 p... 38175809
Bromodomain-containing protein 3 IC50 = 0.88 nM 9.06 Inhibition of C-terminal His6-tagged BRD3 BD2 (unknown origin) using H-YSGRGK(Ac... 35333526
Bromodomain-containing protein 2 IC50 = 0.92 nM 9.04 Inhibition of C-terminal His6-tagged BRD2 BD2 (unknown origin) using H-YSGRGK(Ac... 35333526
Bromodomain-containing protein 4 IC50 = 1.0 nM 9.0 Inhibition of BRD4 BD2 (unknown origin) using biotinylated tetra-acetylated H4 p... 38175809
Bromodomain testis-specific protein Ki = 1.0 nM 9.0 Inhibition of BRDT BD2 (unknown origin) after 1 hr by TR-FRET assay 32324999
Bromodomain-containing protein 3 IC50 = 1.4 nM 8.85 Inhibition of BRD3 BD2 (unknown origin) using biotinylated tetra-acetylated H4 p... 38175809
Bromodomain-containing protein 4 Ki = 1.4 nM 8.85 TR-FRET Assay: Compound dilution series were prepared in DMSO via an approximate... -
Bromodomain-containing protein 4 Ki = 1.4 nM 8.85 TR-FRET Assay: Compound dilution series were prepared in DMSO via an approximate... -
Bromodomain-containing protein 4 Ki = 1.6 nM 8.8 Inhibition of BRD4 BD1 (unknown origin) 33616410
Bromodomain-containing protein 4 Kd = 1.6 nM 8.8 Inhibition of BRD4-BD2 (unknown origin) assessed as dissociation constant by TR-... 35348328
Bromodomain-containing protein 4 Ki = 1.6 nM 8.8 Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expres... 32324999
Bromodomain-containing protein 4 Ki = 1.6 nM 8.8 Inhibition of BRD4 BD2 (unknown origin) 37478496
Bromodomain-containing protein 4 IC50 = 1.78 nM 8.75 Inhibition of BRD4-BD2 (unknown origin) preincubated for 30 mins followed by sub... 35395439
Bromodomain-containing protein 4 Kd = 2.1 nM 8.68 Binding affinity to human partial length BRD4 BD2 expressed in bacterial express... 34236185
Bromodomain-containing protein 2 IC50 = 2.9 nM 8.54 Inhibition of BRDT BD2 (unknown origin) using biotinylated tetra-acetylated H4 p... 38175809
Bromodomain-containing protein 4 IC50 = 3.3 nM 8.48 Inhibition of His-tagged BRD4 bromodomain 2 (unknown origin) using [Lys (5,8,12,... 33077265
Bromodomain-containing protein 2 Ki = 4.6 nM 8.34 Inhibition of N-terminal His6-tagged human BRD2 BD2 (348 to 455 residues) after ... 32324999
Bromodomain-containing protein 3 Ki = 4.9 nM 8.31 Inhibition of BRD3 BD2 (unknown origin) after 1 hr by TR-FRET assay 32324999
Bromodomain-containing protein 4 IC50 = 6.31 nM 8.2 Binding affinity to 6His-Thr-BRD4 (1 to 477 residues) BD2 domain Y390A mutant (u... 34255512

Literature References

PubMed DOI Target Context # Activities
32324999 10.1021/acs.jmedchem.0c00628 ADMET 44
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5058564 Fibroblast 7
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
- 10.6019/CHEMBL5058564 HEK-293T 5
32324999 10.1021/acs.jmedchem.0c00628 Bromodomain-containing protein 4 5
- 10.1158/2159-8290.CD-23-0050 Colon cancer organoid 5
38175809 10.1021/acs.jmedchem.3c02104 Unchecked 4
38175809 10.1021/acs.jmedchem.3c02104 Bromodomain-containing protein 2 4
34255512 10.1021/acs.jmedchem.1c00365 ADMET 4
32353859 10.1038/s41586-020-2286-9 SARS-CoV-2 3
34255512 10.1021/acs.jmedchem.1c00365 No relevant target 3
37478496 10.1021/acs.jmedchem.3c01028 Bromodomain-containing protein 4 2
35348328 10.1021/acs.jmedchem.1c02168 Bromodomain-containing protein 4 2
33077265 10.1016/j.ejmech.2020.112868 MV4-11 2
33077265 10.1016/j.ejmech.2020.112868 Bromodomain-containing protein 4 2
32324999 10.1021/acs.jmedchem.0c00628 Bromodomain testis-specific protein 2
32353859 10.1038/s41586-020-2286-9 Vero C1008 2
33616410 10.1021/acs.jmedchem.0c01487 Bromodomain-containing protein 4 2

Data from ChEMBL 36 via Core Engine