GSK189254

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Search structure


Synonyms	Gsk189254
Status
Molecule Category	Free-form
UNII	5T4TX6CO53


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	WROHEWWOCPRMIA-UHFFFAOYSA-N
Smiles	CNC(=O)c1ccc(Oc2ccc3c(c2)CCN(C2CCC2)CC3)nc1
InChI	InChI=1S/C21H25N3O2/c1-22-21(25)17-6-8-20(23-14-17)26-19-7-5-15-9-11-24(18-3-2-4-18)12-10-16(15)13-19/h5-8,13-14,18H,2-4,9-12H2,1H3,(H,22,25)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C21H25N3O2
Molecular Weight	351.45
AlogP	3.19
Hydrogen Bond Acceptor	4.0
Hydrogen Bond Donor	1.0
Number of Rotational Bond	4.0
Polar Surface Area	54.46
Molecular species	BASE
Aromatic Rings	2.0
Heavy Atoms	26.0

Bioactivity

Mechanism of Action	Action	Reference
Histamine H3 receptor antagonist	ANTAGONIST	PubMed


Protein: Histamine H3 receptor Description: Histamine H3 receptor Organism : Homo sapiens Q9Y5N1 ENSG00000101180

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Ion channel Voltage-gated ion channel Potassium channels Voltage-gated potassium channel	-	-	-	-	36
Membrane receptor Family A G protein-coupled receptor Small molecule receptor (family A GPCR) Monoamine receptor Histamine receptor	-	1	-	0-0	-
Secreted protein	-	-	-	-	60

Assay Description	Organism	Bioactivity	Reference
Binding affinity to histamine H3 receptor	None	0.12 nM
Antagonist activity at human cloned histamine H3 receptor expressed in CHO-K1 cells assessed as inhibition of R-alpha-methylhistamine-induced [35S]GTPgammaS binding	Homo sapiens	0.55 nM
Displacement of [3H]N-R-methylhistamine from human H3 receptor isolated from C6 cells	Homo sapiens	0.26 nM
Binding affinity to rat cortical histamine H3 receptor	Rattus norvegicus	0.631 nM
Binding affinity to human histamine H3 receptor	Homo sapiens	0.1259 nM
Binding affinity to human serum albumin by HPLC analysis	Homo sapiens	60.0 %
Inhibition of human ERG at 10 uM by patch clamp experiment	Homo sapiens	36.0 %
Displacement of [3H]-R-alpha-ethylhistamine from rat histamine H3 receptor expressed in HEK293 cells after 45 mins by liquid scintillation spectrometry	Rattus norvegicus	0.6761 nM
Displacement of [3H]-R-alpha-ethylhistamine from human histamine H3 receptor expressed in HEK293 cells after 45 mins by liquid scintillation spectrometry	Homo sapiens	0.1259 nM
Displacement of [3H]-R-alpha-ethylhistamine from histamine H3 receptor in human cerebral cortical tissue membranes after 45 mins by liquid scintillation spectrometry	Homo sapiens	0.257 nM
Displacement of [3H]-R-alpha-ethylhistamine from histamine H3 receptor in rat cerebral cortical tissue membranes after 45 mins by liquid scintillation spectrometry	Rattus norvegicus	2.63 nM
Antagonist activity at human histamine H3 receptor expressed in CHOK1 cells assessed as inhibition of GTPgammaS binding	Homo sapiens	0.1995 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	14.69 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	0.33 %		Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	0.33 %

Related Entries

Cross References

Resources	Reference
ChEMBL	CHEMBL517140
FDA SRS	5T4TX6CO53
Guide to Pharmacology	10736
SureChEMBL	SCHEMBL169579
ZINC	ZINC000003961799

CONTENTS

PREMIER has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875508. The JU receives support from the EU’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views reflect only the authors’ perspective and the JU is not responsible for any use that may be made of the information this manuscript contains.

Elements of the website have been developed under projects PREMIER and the Biocenter Finland Drug Discovery and Chemical Biology network. CSC-IT is thanked for providing computational resources. Content of the website is provided without guarantee for correctness. Data has been collected and integrated from multiple public sources, for the largest: FDA, HUGO Gene Nomenclature Committee, ChEMBL, IUPHAR/BPS guide to pharmacology, Reactome, UniProt, and Ensembl. Credit is given to Ensembl for collecting species images (provided under public domain licences such as Wikimedia and NHGRI).