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Compound Detail

CHEMBL517140

GSK189254
🧪 Phase II
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🧪 Phase II
CNC(=O)c1ccc(Oc2ccc3c(c2)CCN(C2CCC2)CC3)nc1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL517140
Name GSK189254
Phase Phase II
Structure Type MOL
InChI Key WROHEWWOCPRMIA-UHFFFAOYSA-N

Known Names

GSK-189254 Gsk189254
2
Targets
10
Activities
2
Assay Types
5
PK Parameters
20
Publications
2
Known Names
1
Indications
1
Mechanisms

Molecular Properties

351.4
MW (Da)
3.19
ALogP
4
HBA
1
HBD
54.5
PSA (Ų)
0.92
QED
0
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Extended Properties

Molecular Formula C21H25N3O2
MW 351.45
Aromatic Rings 2
Heavy Atoms 26
NP-Likeness -1.23

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Histamine H3 receptor antagonist ANTAGONIST Histamine H3 receptor ✓ ✓

Indications

Narcolepsy

Activity Summary

Ki 9 meas. best 9.92
IC50 1 meas. best 9.26

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Histamine H3 receptor
CHEMBL264
 Ki 9.92 9.7667 0.1 6
Histamine H3 receptor
CHEMBL264
 IC50 9.26 9.26 0.6 1
Histamine H3 receptor
CHEMBL4124
 Ki 9.2 8.9833 0.6 3

Pharmacokinetic Data

Parameter Value Units Species
AUC 2596.0 ng.hr.mL-1 Rattus norvegicus
CL 0.5 mL.min-1.g-1 Homo sapiens
CL 0.5 mL.min-1.g-1 Rattus norvegicus
Cmax 1237.73 nM Rattus norvegicus
F 51.0 % Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Histamine H3 receptor Ki = 0.12 nM 9.92 Binding affinity to histamine H3 receptor 19456097
Histamine H3 receptor Ki = 0.1259 nM 9.9 Binding affinity to human histamine H3 receptor 21062081
Histamine H3 receptor Ki = 0.1259 nM 9.9 Displacement of [3H]-R-alpha-ethylhistamine from human histamine H3 receptor exp... 24269482
Histamine H3 receptor Ki = 0.1995 nM 9.7 Antagonist activity at human histamine H3 receptor expressed in CHOK1 cells asse... 24269482
Histamine H3 receptor Ki = 0.26 nM 9.59 Displacement of [3H]N-R-methylhistamine from human H3 receptor isolated from C6 ... 20945906
Histamine H3 receptor Ki = 0.257 nM 9.59 Displacement of [3H]-R-alpha-ethylhistamine from histamine H3 receptor in human ... 24269482
Histamine H3 receptor IC50 = 0.55 nM 9.26 Antagonist activity at human cloned histamine H3 receptor expressed in CHO-K1 ce... 18841880
Histamine H3 receptor Ki = 0.631 nM 9.2 Binding affinity to rat cortical histamine H3 receptor 21062081
Histamine H3 receptor Ki = 0.6761 nM 9.17 Displacement of [3H]-R-alpha-ethylhistamine from rat histamine H3 receptor expre... 24269482
Histamine H3 receptor Ki = 2.63 nM 8.58 Displacement of [3H]-R-alpha-ethylhistamine from histamine H3 receptor in rat ce... 24269482

Literature References

PubMed DOI Target Context # Activities
24269482 10.1016/j.bmcl.2013.09.090 Histamine H3 receptor 5
24269482 10.1016/j.bmcl.2013.09.090 Rattus norvegicus 4
21824776 10.1016/j.bmcl.2011.06.094 Rattus norvegicus 3
- 10.6019/CHEMBL4495565 SARS-CoV-2 2
21062081 10.1021/jm100064d Histamine H3 receptor 2
24269482 10.1016/j.bmcl.2013.09.090 Liver microsome 2
24269482 10.1016/j.bmcl.2013.09.090 ADMET 1
24269482 10.1016/j.bmcl.2013.09.090 Blood 1
24269482 10.1016/j.bmcl.2013.09.090 Histamine H1 receptor 1
24269482 10.1016/j.bmcl.2013.09.090 Histamine H2 receptor 1
24269482 10.1016/j.bmcl.2013.09.090 Histamine H4 receptor 1
24269482 10.1016/j.bmcl.2013.09.090 Voltage-gated inwardly rectifying potassium channel KCNH2 1
24269482 10.1016/j.bmcl.2013.09.090 No relevant target 1
18841880 10.1021/jm800569w Histamine H3 receptor 1
24269482 10.1016/j.bmcl.2013.09.090 Albumin 1
24076172 10.1016/j.bmcl.2013.09.006 Rattus norvegicus 1
21824776 10.1016/j.bmcl.2011.06.094 Nucleic Acid 1
21824776 10.1016/j.bmcl.2011.06.094 Brain 1
20945906 10.1021/jm100666w Histamine H3 receptor 1
19456097 10.1021/jm900409x Histamine H3 receptor 1

Data from ChEMBL 36 via Core Engine