SELONSERTIB

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Search structure


Synonyms	GS-4997 Gs-4997 Selonsertib
Status
Molecule Category	UNKNOWN
UNII	NS3988A2TC


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

Structure


InChI Key	YIDDLAAKOYYGJG-UHFFFAOYSA-N
Smiles	Cc1cc(F)c(C(=O)Nc2cccc(-c3nncn3C(C)C)n2)cc1-n1cnc(C2CC2)c1
InChI	InChI=1S/C24H24FN7O/c1-14(2)32-13-27-30-23(32)19-5-4-6-22(28-19)29-24(33)17-10-21(15(3)9-18(17)25)31-11-20(26-12-31)16-7-8-16/h4-6,9-14,16H,7-8H2,1-3H3,(H,28,29,33)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C24H24FN7O
Molecular Weight	445.5
AlogP	4.68
Hydrogen Bond Acceptor	7.0
Hydrogen Bond Donor	1.0
Number of Rotational Bond	6.0
Polar Surface Area	90.52
Molecular species	NEUTRAL
Aromatic Rings	4.0
Heavy Atoms	33.0

Bioactivity

Mechanism of Action	Action	Reference
Mitogen-activated protein kinase kinase kinase 5 inhibitor	INHIBITOR	PubMed


Protein: Mitogen-activated protein kinase kinase kinase 5 Description: Mitogen-activated protein kinase kinase kinase 5 Organism : Homo sapiens Q99683 ENSG00000197442

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Kinase Protein Kinase STE protein kinase group STE protein kinase STE11 family STE protein kinase ASK	-	6247	-	-	-
Enzyme Kinase Protein Kinase STE protein kinase group STE protein kinase STE11 family	2	3-24	-	-	-

Assay Description	Organism	Bioactivity	Reference
Inhibition of recombinant human N-terminal GST-tagged ASK1 catalytic domain (654 to 971 residues) expressed in baculovirus infected sf21 cells using STK3 as substrate after 60 mins by HTRF assay	Homo sapiens	5.012 nM
Inhibition of ASK1 (unknown origin) using biotin-MBP as substrate after 20 mins by TR-FRET assay	Homo sapiens	5.0 nM
Inhibition of ASK1 (unknown origin)	Homo sapiens	6.0 nM
Inhibition of human ASK1 using myelin basic protein substrate pre-incubated for 20 mins before [33P]-ATP addition and measured after 2 hrs by filter-binding method	Homo sapiens	5.9 nM
Inhibition of V5 tagged human ASK1 expressed in HEK-293T cells assessed as reduction in T838 autophosphorylation incubated for 1 hr	Homo sapiens	20.0 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	6.84 %
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	-0.28 %		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	-0.28 %
Inhibition of V5 tagged human ASK1 expressed in HEK293T cells assessed as reduction in T848 autophosphorylation incubated for 1 hr by MSD assay	Homo sapiens	20.0 nM
Inhibition of human ASK1 using myelin basic protein substrate preincubated for 20 mins before [33P]-ATP addition and measured after 2 hrs by filter-binding method	Homo sapiens	5.5 nM
Inhibition of ASK1 (unknown origin)	Homo sapiens	24.4 nM
Inhibition of ASK1 (unknown origin) by competitive TR-FRET assay	Homo sapiens	5.0 nM
Inhibition of ASK1 (unknown origin)	Homo sapiens	3.0 nM
Inhibition of ASK1 (unknown origin) by cell based assay	Homo sapiens	2.0 nM
Inhibition of ASK1 in human HEK293 cells transfected with AP1 assessed as inhibition of AP1-induced luciferase activity at 10 uM preincubated for 1 hr followed by PMA stimulation and measured after 6 hrs by luciferase reporter assay	Homo sapiens	76.67 %
Inhibition of ASK1 (unknown origin)	Homo sapiens	5.9 nM
Inhibition of human full length recombinant ASK1 using STK-Substrate-3 biotin as substrate in presence of ATP measured after 2 hrs by HTRP kinase assay	Homo sapiens	12.9 nM
Inhibition of ASK1 in human HEK293 cells transfected with AP1 assessed as inhibition of AP1-induced firefly luciferase activity at 10 uM preincubated for 1 hr followed by PMA stimulation and measured after 6 hrs by luciferase reporter assay relative to control	Homo sapiens	76.7 %

Cross References

Resources	Reference
ChEMBL	CHEMBL3916717
DrugBank	DB14916
FDA SRS	NS3988A2TC
Guide to Pharmacology	9040
PDB	NJV
PubChem	71245288
SureChEMBL	SCHEMBL14672984
ZINC	ZINC000149387856

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).