WNT-974

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Search structure


Synonyms	LGK-974 LGK974 Lgk974 WNT974 Wnt-974 Wnt974
Status
Molecule Category	UNKNOWN
UNII	U27F40013Q


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

Structure


InChI Key	XXYGTCZJJLTAGH-UHFFFAOYSA-N
Smiles	Cc1cc(-c2ncc(CC(=O)Nc3ccc(-c4cnccn4)cn3)cc2C)ccn1
InChI	InChI=1S/C23H20N6O/c1-15-9-17(12-28-23(15)18-5-6-25-16(2)10-18)11-22(30)29-21-4-3-19(13-27-21)20-14-24-7-8-26-20/h3-10,12-14H,11H2,1-2H3,(H,27,29,30)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C23H20N6O
Molecular Weight	396.45
AlogP	3.79
Hydrogen Bond Acceptor	6.0
Hydrogen Bond Donor	1.0
Number of Rotational Bond	5.0
Polar Surface Area	93.55
Molecular species	NEUTRAL
Aromatic Rings	4.0
Heavy Atoms	30.0

Bioactivity

Mechanism of Action	Action	Reference
Probable protein-cysteine N-palmitoyltransferase porcupine inhibitor	INHIBITOR	PubMed PubMed ClinicalTrials


Protein: Probable protein-cysteine N-palmitoyltransferase porcupine Description: Protein-serine O-palmitoleoyltransferase porcupine Organism : Homo sapiens Q9H237 ENSG00000102312

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Transferase	-	0-1	-	-	-

Assay Description	Organism	Bioactivity	Reference
Inhibition of porcupine activity (unknown origin) expressed in human HT1080 cells assessed as suppression of Wnt3A-mediated super top flash activity by STF luciferase assay	Homo sapiens	0.4 nM
Inhibition of Wnt signaling (unknown origin) expressed in mouse L Wnt3A cells co-cultured with HEK293 cells after 48 hrs by Super-top flash reporter gene assay	Homo sapiens	0.9 nM
Inhibition of porcupine in mouse L Wnt3A cells co-cultured with HEK293 cells after 48 hrs by Super-top flash reporter gene assay	Mus musculus	0.9 nM
Inhibition of porcupine (unknown origin)	Homo sapiens	0.4 nM
Inhibition of porcupine in mouse L Wnt3A cells co-cultured with HEK293 cells assessed as suppression of Wnt signaling after 48 hrs by Super-top flash reporter gene assay	Mus musculus	0.9 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging	Homo sapiens	104.98 %
Inhibition of Wnt/beta-catenin pathway in mouse L Wnt3A cells at 10 uM after 48 hrs by TOP-flash dual reporter gene assay relative to control	Mus musculus	93.0 %
Inhibition of Wnt/beta-catenin pathway in mouse L Wnt3A cells after 48 hrs by TOP-flash dual reporter gene assay	Mus musculus	0.57 nM
Inhibition of PORCN in mouse Leydig cells overexpressing Wnt3A co-cultured with TM3 cells transfected with Wnt-luciferase gene after 24 hrs by luminescence assay	Mus musculus	0.4 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	30.89 %		SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	-21.55 %
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	-0.06 %		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	0.19 %		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	0.19 %		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	-0.06 %

Cross References

Resources	Reference
ChEBI	78030
ChEMBL	CHEMBL3188386
DrugBank	DB12561
FDA SRS	U27F40013Q
Guide to Pharmacology	11167
PubChem	46926973
SureChEMBL	SCHEMBL1723611
ZINC	ZINC000095930187

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).