PF-04937319

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Search structure


Synonyms	Pf-04937319
Status
Molecule Category	Free-form
UNII	7E99B9ZM19


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

Structure


InChI Key	MASKQITXHVYVFL-UHFFFAOYSA-N
Smiles	Cc1cnc(NC(=O)c2cc(Oc3cnc(C(=O)N(C)C)nc3)c3cc(C)oc3c2)cn1
InChI	InChI=1S/C22H20N6O4/c1-12-8-24-19(11-23-12)27-21(29)14-6-17-16(5-13(2)31-17)18(7-14)32-15-9-25-20(26-10-15)22(30)28(3)4/h5-11H,1-4H3,(H,24,27,29)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C22H20N6O4
Molecular Weight	432.44
AlogP	3.38
Hydrogen Bond Acceptor	8.0
Hydrogen Bond Donor	1.0
Number of Rotational Bond	5.0
Polar Surface Area	123.34
Molecular species	NEUTRAL
Aromatic Rings	4.0
Heavy Atoms	32.0

Bioactivity

Mechanism of Action	Action	Reference
Hexokinase type IV activator	ACTIVATOR	PubMed


Protein: Hexokinase type IV Description: Hexokinase-4 Organism : Homo sapiens P35557 ENSG00000106633

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme	174-1090	-	189	-	-
Ion channel Voltage-gated ion channel Potassium channels Voltage-gated potassium channel	-	-	-	-	0

Assay Description	Organism	Bioactivity	Reference
Activation of human recombinant glucokinase using 6.5 mM glucose by spectrophotometric analysis	Homo sapiens	188.0 nM
Induction of glucokinase translocation from nucleus to cytoplasm in cryopreserved rat hepatocytes after 1 hr by Hoechst staining-based fluorescence microscopic analysis	Rattus norvegicus	900.0 nM
Activation of human recombinant glucokinase by matrix assay in presence of glucose	Homo sapiens	190.0 nM
Activation of recombinant human glucokinase assessed as formation of glucose-6-phosphate by G6PDH/NADP coupled assay	Homo sapiens	188.0 nM
Activation of rat glucokinase	Rattus norvegicus	407.0 nM
Inhibition of dofetilide binding to human ERG at 10 uM relative to control	Homo sapiens	0.0 %
Induction of glucokinase translocation from nucleus to cytoplasm in rat hepatocytes in presence of 8.9 mM glucose	Rattus norvegicus	900.0 nM
Induction of glucokinase translocation from nucleus to cytoplasm in rat hepatocytes in presence of 15 mM glucose	Rattus norvegicus	600.0 nM
Binding affinity to biotinylated human recombinant glucokinase expressed in Escherichia coli assessed as dissociation rate constant by SPR method	Homo sapiens	189.2 nM
Activation of recombinant human glucokinase assessed as formation of glucose-6-phosphate by G6PDH/NADP coupled assay	Homo sapiens	174.0 nM
Activation of recombinant human liver glucokinase 2 assessed as reduction in NADH production in presence of 5 mM glucose by G6PDH coupled assay	Homo sapiens	930.0 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	-4.84 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	8.831 %
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	-0.16 %		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	-0.16 %

Cross References

Resources	Reference
ChEMBL	CHEMBL2165615
DrugBank	DB15009
FDA SRS	7E99B9ZM19
PDB	S41
PubChem	46916694
SureChEMBL	SCHEMBL1720691
ZINC	ZINC000068246554

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).