LUVADAXISTAT

/static/temp/default.svg

Search structure


Synonyms	Luvadaxistat TAK-831 TAK831 Tak-831
Status
Molecule Category	UNKNOWN
UNII	76IC00YRVR


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

Structure


InChI Key	QBQMUMMSYHUDFM-UHFFFAOYSA-N
Smiles	O=c1[nH]nc(CCc2ccc(C(F)(F)F)cc2)cc1O
InChI	InChI=1S/C13H11F3N2O2/c14-13(15,16)9-4-1-8(2-5-9)3-6-10-7-11(19)12(20)18-17-10/h1-2,4-5,7H,3,6H2,(H,17,19)(H,18,20)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C13H11F3N2O2
Molecular Weight	284.24
AlogP	2.28
Hydrogen Bond Acceptor	3.0
Hydrogen Bond Donor	2.0
Number of Rotational Bond	3.0
Polar Surface Area	65.98
Molecular species	NEUTRAL
Aromatic Rings	2.0
Heavy Atoms	20.0

Assay Description	Organism	Bioactivity	Reference
Inhibition of rat full length DAAO overexpressed in HEK293 cells after 30 mins by plate reader analysis	Rattus norvegicus	5.0 nM
Inhibition of mouse full length DAAO overexpressed in HEK293 cells after 30 mins by plate reader analysis	Mus musculus	5.9 nM
Inhibition of human full length DAAO overexpressed in HEK293 cells after 30 mins by plate reader analysis	Homo sapiens	27.0 nM
Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	Homo sapiens	12.0 nM
Inhibition Assay: The DAAO inhibitory activity was measured by assaying the amount of hydrogen peroxide (H2O2) produced by reacting DAAO protein with flavin adenine dinucleotide (FAD) and D-alanine. The amount of H2O2 was determined by measuring the fluorescence generated on conversion of Amplex red (manufactured by Invitrogen Co.) into resorufin by the reaction of H2O2 with horseradish peroxidase (HRP). 4 uL of 4% dimethyl sulfoxide (DMSO) buffer (50 mM sodium phosphate (pH 7.5), 0.02% CHAPS) solution of the test compound was added to 384-well black, low volume plate, a mixed solution (4 uL) of recombinant human DAAO protein (15 nM), which had been expressed in Escherichia coli and purified, and 18 uM FAD was added, and the mixture was incubated at room temperature for 15 min. After incubation, a mixed buffer (4 uL) of 2.25 mM D-alanine, 1.5 U/mL HRP and 150 uM Amplex red was added, the mixture was incubated at room temperature for 30 min.	Homo sapiens	12.0 nM
Inhibition Assay: This test was performed by partially modifying the method of Philip et. al. (J. Biomol. Screen. Vol. 11, pp 481-487, 2006). HEK293 cells that stably express human DAAO were suspended in Cellbanker solution at 5×106 cells/ml and cryopreserved at −80° C. At the time of measurement, the cells were centrifuged at 1000 rpm for one min and the Cellbanker solution was removed. The cells were resuspended at 5×106 cells/ml in FAD-containing buffer (50 mM sodium phosphate [pH 7.5], 18 μM FAD, 0.02% CHAPS). A 4% DMSO buffer solution (50 mM sodium phosphate [pH 7.5], 0.02% CHAPS) of the test compound (4 μL) was added to a 384-well black, low volume plate, the cell suspension (4 μL) was added, and the mixture was incubated at room temperature for 15 min. After incubation, a mixed buffer (4 μL) of 150 mM D-alanine, 1.5 U/mL HRP and 240 μM Amplex red was added to the plate, and the mixture was incubated at room temperature for 30 min, and the fluorescence (excitation w	Homo sapiens	27.0 nM
In Vitro DAAO Enzyme Assay: Human DAAO enzyme was supplied by the Takeda Pharmaceutical Company (Osaka) and each batch was tested and used at concentrations giving comparable levels of activity. The Km of D-Serine was measured for each enzyme batch to maintain consistency; this Km was used in subsequent assays.On the day of the assay compounds were serially diluted in DMSO before being diluted 1:20 with assay buffer (20 mM Tris ph 7.4). A 5 ul portion of assay buffer was added to the wells of a 384 clear base black-walled plate (Corning), 5 ul of diluted compound was then added via automated plate to plate transfer using the Bravo liquid handler (Agilent technologies) followed by 5 ul of human DAAO enzyme and then 5 ul D-Serine 50 mM was added to all but the negative control wells (final concentration of 10 mM). Finally 5 ul Amplex red reagent (Invitrogen) was added to all wells as per manufacturer's protocol. The plate was incubated for 60 minutes in the dark at 25° C., and the fluorescence in each well was measured in the Envision plate reader.	Homo sapiens	19.0 nM

Cross References

Resources	Reference
ChEMBL	CHEMBL2338801
DrugBank	DB16067
FDA SRS	76IC00YRVR
PubChem	71270546
SureChEMBL	SCHEMBL14719667
ZINC	ZINC000095592350

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).