LINERIXIBAT

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Search structure


Synonyms	GSK2330672 Gsk-2330672 Gsk2330672 Linerixibat
Status
Molecule Category	UNKNOWN
UNII	386012Z45S


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

Structure


InChI Key	CZGVOBIGEBDYTP-VSGBNLITSA-N
Smiles	CCCC[C@]1(CC)CS(=O)(=O)c2cc(CNC(CC(=O)O)CC(=O)O)c(OC)cc2[C@@H](c2ccccc2)N1
InChI	InChI=1S/C28H38N2O7S/c1-4-6-12-28(5-2)18-38(35,36)24-13-20(17-29-21(14-25(31)32)15-26(33)34)23(37-3)16-22(24)27(30-28)19-10-8-7-9-11-19/h7-11,13,16,21,27,29-30H,4-6,12,14-15,17-18H2,1-3H3,(H,31,32)(H,33,34)/t27-,28-/m1/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C28H38N2O7S
Molecular Weight	546.69
AlogP	3.91
Hydrogen Bond Acceptor	7.0
Hydrogen Bond Donor	4.0
Number of Rotational Bond	13.0
Polar Surface Area	142.03
Molecular species	ACID
Aromatic Rings	2.0
Heavy Atoms	38.0

Bioactivity

Mechanism of Action	Action	Reference
Ileal bile acid transporter inhibitor	INHIBITOR	PubMed


Protein: Ileal bile acid transporter Description: Ileal sodium/bile acid cotransporter Organism : Homo sapiens Q12908 ENSG00000125255

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC10 family of sodium-bile acid co-transporters	-	2	-	-	-

Assay Description	Organism	Bioactivity	Reference
Inhibition of rat ASBT expressed in HEK293 cells assessed as inhibition of [3H]-taurocholate uptake after 90 mins by scintillation counting analysis	Rattus norvegicus	1.9 nM
Inhibition of mouse ASBT expressed in HEK293 cells assessed as inhibition of [3H]-taurocholate uptake after 90 mins by scintillation counting analysis	Mus musculus	2.1 nM
Inhibition of human ASBT expressed in HEK293 cells assessed as inhibition of [3H]-taurocholate uptake after 90 mins by scintillation counting analysis	Homo sapiens	42.0 nM
Inhibition Assay: On the day of the uptake experiment, 10 mM HEPES was added to Hank's Balanced Salt Solution, and the pH was adjusted to 7.4 with TRIS (HBSSH). The assay buffer was prepared by adding 100 uM [3H]-taurocholate and 10 uM cold taurocholate to room temperature HBSSH. A separate washing buffer was prepared by adding 10 uM cold taurocholate to HBSSH (30 ml per assay plate) and placed on ice. Using 100% DMSO, 8 point, 3-fold dilution curves for each test compound was prepared starting at 200 uM. Similarly, an 8 point dose response curve was prepared of the control compound [(3R,5R)-3-butyl-3-ethyl-7,8-bis(methyloxy)-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (Brieaddy, L. E. WO9605188, 1996)] starting at 1.8 mM. Drug plates were created by adding 3 uL of each concentration to a v-bottom 96-well plate then diluted 60-fold with 177 uL of assay buffer. Plates were removed from the incubator and allowed to cool to ambient temperature.	None	43.0 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	1.5 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	4.29 %		SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	19.25 %
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	-0.1 %		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	-0.23 %		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	-0.1 %		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	-0.23 %

Cross References

Resources	Reference
ChEMBL	CHEMBL2387408
DrugBank	DB11729
FDA SRS	386012Z45S
PubChem	53492727
SureChEMBL	SCHEMBL2586025
ZINC	ZINC000096270862

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).