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Compound Detail

CHEMBL2017291

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COc1cc2c(cc1-c1c(C)noc1C)ncc1[nH]c(=O)n([C@H](C)c3ccccn3)c12

Basic Information

ChEMBL ID CHEMBL2017291
Phase Preclinical
Structure Type MOL
InChI Key VUVUVNZRUGEAHB-CYBMUJFWSA-N

Known Names

GSK1210151A
36
Targets
189
Activities
4
Assay Types
30
PK Parameters
20
Publications
1
Known Names

Molecular Properties

415.4
MW (Da)
4.16
ALogP
7
HBA
1
HBD
98.8
PSA (Ų)
0.47
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 C23H21N5O3
MW 415.45
Aromatic Rings 5
Heavy Atoms 31
NP-Likeness -1.04

Activity Summary

IC50 167 meas. best 7.82
Kd 11 meas. best 7.7
Ki 10 meas. best 8.14
EC50 1 meas. best 5.16

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Bromodomain-containing protein 3
CHEMBL1795186
Ki 8.14 7.895 7.2 2
Bromodomain-containing protein 4
CHEMBL1163125
Ki 8.05 7.3317 9.0 6
Bromodomain-containing protein 2
CHEMBL1293289
Ki 8.05 7.675 9.0 2
Bromodomain-containing protein 3
CHEMBL1795186
IC50 7.82 6.5818 15.0 17
NOMO-1
CHEMBL2366198
IC50 7.82 7.82 15.0 1
Bromodomain testis-specific protein
CHEMBL1795185
IC50 7.82 6.4158 15.0 12
Bromodomain-containing protein 4
CHEMBL1163125
IC50 7.82 6.7453 15.0 45
Bromodomain-containing protein 2
CHEMBL1293289
IC50 7.82 6.4582 15.0 17
Bromodomain-containing protein 3
CHEMBL1795186
Kd 7.7 7.58 20.0 4
MV4-11
CHEMBL613835
IC50 7.58 6.9575 26.0 8
Unchecked
CHEMBL612545
IC50 7.52 6.628 30.0 5
C-C motif chemokine 2
CHEMBL1649052
IC50 7.4 7.05 39.8 2
PBMC
CHEMBL613107
IC50 7.4 7.0 39.8 3
Bromodomain-containing protein 4
CHEMBL1163125
Kd 7.28 6.9875 52.8 4
Bromodomain-containing protein 2
CHEMBL1293289
Kd 7.26 7.205 54.8 2
MOLM-13
CHEMBL3706572
IC50 6.92 6.78 120.0 2
HL-60
CHEMBL383
IC50 6.9 6.5533 125.9 3
THP-1
CHEMBL614245
IC50 6.87 6.87 134.2 1
RS4-11
CHEMBL2366159
IC50 6.72 6.72 192.0 1
Blood
CHEMBL613416
IC50 6.7 6.255 199.5 6
Mus musculus
CHEMBL375
IC50 6.64 6.64 228.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 6.52 6.52 299.0 1
HT-29
CHEMBL384
IC50 6.03 6.03 945.0 1
HEL
CHEMBL613888
IC50 6.0 6.0 1000.0 1
Blood
CHEMBL613615
IC50 5.9 5.9 1260.0 1
Voltage-dependent P/Q-type calcium channel subunit alpha-1A
CHEMBL4266
IC50 5.9 5.9 1260.0 1
Acetylcholine receptor subunit alpha
CHEMBL4808
IC50 5.9 5.9 1260.0 1
CREB-binding protein
CHEMBL5747
Kd 5.51 5.51 3084.0 1
3',5'-cyclic-AMP phosphodiesterase 4B
CHEMBL275
IC50 5.44 5.4267 3630.0 3
Cytochrome P450 2C9
CHEMBL3397
IC50 5.38 5.152 4170.0 5
Unchecked
CHEMBL612545
EC50 5.16 5.16 7000.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 5.01 4.8 9700.0 8
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.0 4.8 10000.0 3
Substance-P receptor
CHEMBL249
IC50 4.9 4.9 12600.0 2
Solute carrier organic anion transporter family member 1B1
CHEMBL1697668
IC50 4.9 4.9 12600.0 2
Potassium voltage-gated channel subfamily A member 5
CHEMBL4306
IC50 4.8 4.8 15800.0 2
Cytochrome P450 2C19
CHEMBL3622
IC50 4.78 4.78 16596.0 1
MEG-01
CHEMBL2366084
IC50 4.6 4.6 25000.0 1
Vasopressin V1a receptor
CHEMBL1889
IC50 4.5 4.5 31600.0 2
Cytochrome P450 2D6
CHEMBL289
IC50 4.42 4.42 38020.0 2
Voltage-gated inwardly rectifying potassium channel KCNH3
CHEMBL2363017
IC50 4.4 4.4 40000.0 1
Amine oxidase [flavin-containing] B
CHEMBL2039
IC50 4.3 4.3 50000.0 2
Sodium channel protein type 5 subunit alpha
CHEMBL1980
IC50 4.1 4.1 79400.0 2

Pharmacokinetic Data

Parameter Value Units Species
AUC 282506.0 ng.hr.mL-1 Mus musculus
AUC 6231.75 ng.hr.mL-1 Mus musculus
AUC 6356.39 ng.hr.mL-1 Mus musculus
AUC 7561.19 ng.hr.mL-1 Mus musculus
AUC 7935.1 ng.hr.mL-1 Mus musculus
AUC 955.53 ng.hr.mL-1 Rattus norvegicus
AUC 997.08 ng.hr.mL-1 Rattus norvegicus
AUC 1163.26 ng.hr.mL-1 Rattus norvegicus
AUC 1204.8 ng.hr.mL-1 Rattus norvegicus
AUC 457.0 ng.hr.mL-1 Canis lupus familiaris
AUC 498.54 ng.hr.mL-1 Canis lupus familiaris
AUC 207.72 ng.hr.mL-1 Canis lupus familiaris
AUC 124.63 ng.hr.mL-1 Canis lupus familiaris
AUC 282090.55 ng.hr.mL-1 Mus musculus
CL 18.0 mL.min-1.kg-1 Rattus norvegicus
CL 8.0 mL.min-1.kg-1 Mus musculus
CL 15.0 mL.min-1.kg-1 Sus scrofa
CL 38.0 mL.min-1.kg-1 Canis lupus familiaris
CL 18.0 mL.min-1.kg-1 Rattus norvegicus
CL 0.86 mL.min-1.kg-1 Homo sapiens
CL 0.86 mL.min-1.kg-1 Sus scrofa
CL 9.8 mL.min-1.kg-1 Canis lupus familiaris
CL 0.86 mL.min-1.kg-1 Rattus norvegicus
CL 1.1 mL.min-1.kg-1 Homo sapiens
CL 0.53 mL.min-1.kg-1 Sus scrofa
CL 17.0 mL.min-1.kg-1 Canis lupus familiaris
CL 0.53 mL.min-1.kg-1 Rattus norvegicus
CL 3.24 uL.min-1.(10^6cells)-1 Homo sapiens
CL 3.39 uL.min-1.(10^6cells)-1 Rattus norvegicus
CL 7.59 mL.min-1.g-1 Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Bromodomain-containing protein 3 Ki = 7.2 nM 8.14 Displacement of FAM-labeled ZBA248 from BRD3 BD1 (24 to 144 amino acid residues)... 26080064
Bromodomain-containing protein 2 Ki = 9.0 nM 8.05 Displacement of FAM-labeled ZBA248 from BRD2 BD1 (72 to 205 amino acid residues)... 26080064
Bromodomain-containing protein 4 Ki = 9.0 nM 8.05 Displacement of FAM-labeled ZBA248 from BRD4 BD1 (44 to 168 amino acid residues)... 26080064
Bromodomain-containing protein 4 Ki = 9.0 nM 8.05 Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-ta... 28463487
Bromodomain-containing protein 2 IC50 = 15.0 nM 7.82 Affinity Phenotypic Cellular interaction: (Inhibition of MLL-fusion leukemic NOM... -
Bromodomain-containing protein 3 IC50 = 15.0 nM 7.82 Affinity Phenotypic Cellular interaction: (Inhibition of MLL-fusion leukemic NOM... -
Bromodomain-containing protein 4 IC50 = 15.0 nM 7.82 Affinity Phenotypic Cellular interaction: (Inhibition of MLL-fusion leukemic NOM... -
Bromodomain testis-specific protein IC50 = 15.0 nM 7.82 Affinity Phenotypic Cellular interaction: (Inhibition of MLL-fusion leukemic NOM... -
NOMO-1 IC50 = 15.0 nM 7.82 Antiproliferative activity against human NOMO-1 cells harboring MLL-AF9 assessed... 21964340
Bromodomain-containing protein 4 IC50 = 18.0 nM 7.75 Inhibition of His-FLAG-tagged BRD4 binding domain1 (unknown origin) binding to H... 24900758
Bromodomain-containing protein 4 IC50 = 18.0 nM 7.75 Inhibition of BRD4 bromodomain 1 (unknown origin) 26572217
Bromodomain-containing protein 4 IC50 = 18.0 nM 7.75 Inhibition of His/FLAG-tagged BRD4 BD1 (unknown origin) using histone H4-TetraAc... 26985289
Bromodomain-containing protein 3 Kd = 20.0 nM 7.7 Selectivity interaction (SPR measurement) EUB0000102c BRD3 -
Bromodomain-containing protein 3 Kd = 20.0 nM 7.7 Binding affinity to His6-tagged BRD3 (1 to 434 residues) (unknown origin) at pH ... 21964340
Bromodomain-containing protein 3 Ki = 22.3 nM 7.65 Displacement of FAM-labeled ZBA248 from BRD3 BD2 (306 to 417 amino acid residues... 26080064
Bromodomain-containing protein 4 IC50 = 25.12 nM 7.6 Inhibition of BDR4-BD1 (unknown origin) by TR-FRET assay 34547507
Bromodomain-containing protein 4 IC50 = 25.0 nM 7.6 Displacement of Biotin-tagged [Lys(5,8,12,16)Ac]H4(1 to 21) peptide from GST-tag... 37659219
Bromodomain-containing protein 4 IC50 = 25.12 nM 7.6 Inhibition of BRD4 BD1 (unknown origin) by TR-FRET assay 37736196
Bromodomain-containing protein 4 IC50 = 25.12 nM 7.6 Displacement of Alexa Fluor 647 labelled ligand from recombinant human N-termina... 34387088
Bromodomain-containing protein 4 IC50 = 25.12 nM 7.6 Displacement of Alexa Fluor 647 labelled I-BET762 from N-terminal His6-tagged hu... 32787145

Literature References

PubMed DOI Target Context # Activities
21964340 10.1038/nature10509 ADMET 45
21964340 10.1038/nature10509 Unchecked 44
21964340 10.1038/nature10509 MV4-11 28
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
- 10.6019/CHEMBL5444388 Bromodomain testis-specific protein 11
- 10.6019/CHEMBL5444388 Bromodomain-containing protein 3 11
- 10.6019/CHEMBL5444388 Bromodomain-containing protein 2 11
- 10.6019/CHEMBL5444388 Bromodomain-containing protein 4 11
21964340 10.1038/nature10509 MOLM-13 9
- 10.6019/CHEMBL4689842 U2OS 9
21964340 10.1038/nature10509 K562 9
22437115 10.1016/j.bmcl.2012.02.041 Salmonella typhimurium 8
22437115 10.1016/j.bmcl.2012.02.041 Blood 8
- 10.6019/CHEMBL4689842 Fibroblast 8
30108844 10.1039/C7MD00083A MV4-11 7
22437115 10.1016/j.bmcl.2012.02.041 Mus musculus 7
- 10.6019/CHEMBL4689842 HEK-293T 7
26080064 10.1021/acs.jmedchem.5b00613 Bromodomain-containing protein 4 6
21964340 10.1038/nature10509 Bromodomain-containing protein 4 6

Data from ChEMBL 36 via Core Engine