ASLAN-003

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Search structure


Synonyms	ASLAN003 Aslan-003 Aslan003 Farudodstat
Status
Molecule Category	UNKNOWN
UNII	I58WE41H6X


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

Structure


InChI Key	OMPATGZMNFWVOH-UHFFFAOYSA-N
Smiles	COc1cccc(-c2cc(F)c(Nc3ncccc3C(=O)O)c(F)c2)c1
InChI	InChI=1S/C19H14F2N2O3/c1-26-13-5-2-4-11(8-13)12-9-15(20)17(16(21)10-12)23-18-14(19(24)25)6-3-7-22-18/h2-10H,1H3,(H,22,23)(H,24,25)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C19H14F2N2O3
Molecular Weight	356.33
AlogP	4.48
Hydrogen Bond Acceptor	4.0
Hydrogen Bond Donor	2.0
Number of Rotational Bond	5.0
Polar Surface Area	71.45
Molecular species	ACID
Aromatic Rings	3.0
Heavy Atoms	26.0

Bioactivity

Mechanism of Action	Action	Reference
Dihydroorotate dehydrogenase inhibitor	INHIBITOR	ClinicalTrials PubMed


Protein: Dihydroorotate dehydrogenase Description: Dihydroorotate dehydrogenase (quinone), mitochondrial Organism : Homo sapiens Q02127 ENSG00000102967

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Oxidoreductase	-	15	-	-	-

Assay Description	Organism	Bioactivity	Reference
Inhibition of Homo sapiens (human) dehydroorotate dihydrogenase using 2,6-dichlorophenol-indophenol as substrate after 10 min by spectrophotometric analysis	Homo sapiens	15.0 nM
Inhibition Assay: DHODH activity and its inhibition were studied using a chromogen reduction assay with DCIP (2,6-dichlorophenol-indophenol). The substrate oxidation (Dihydroorotate, L-DHO), as well as cosubstrate reduction (coenzyme Q, CoQ) is coupled to the chromogen reduction, hence enzymatic activity results in a loss of chromogen absorbance at 600 nm. Enzyme extracts (8 μl, 1.5 μg of human protein) were incubated in 96-well plates. The assay mixture (200 μl) contained 200 μM CoQD, 100 μM L-DHO, 120 μM DCIP in the assay buffer (100 mM HEPES pH 8.0, 150 mM NaCl, 10% Glicerol, 0.05% Triton X-100) and 2 μl of test compound. The compounds were dissolved in DMSO at a stock concentration of 1 mM, and tested at different concentrations varying from 10 μM to 1 μM to calculate an IC50 (concentration of inhibitor required for 50% of inhibition).	Homo sapiens	15.0 nM
Inhibition of human recombinant N-terminal GST-tagged DHODH expressed in Escherichia coli BL21(DE3) using dihydroorotate substrate preincubated for 5 mins followed by substrate addition by DCIP assay	Homo sapiens	35.0 nM
Inhibition of human DHODH using dihydroorotate substrate preincubated for 30 mins followed by substrate addition by DCIP based microplate reader analysis	Homo sapiens	44.0 nM
Antiproliferative activity against human A549 cells assessed as cell growth inhibition incubated for 96 hrs by MTT assay	Homo sapiens	900.0 nM
Antiproliferative activity against human Raji cells assessed as cell growth inhibition incubated for 96 hrs by MTT assay	Homo sapiens	300.0 nM
Antiproliferative activity against human A-375 cells assessed as cell growth inhibition incubated for 96 hrs by MTT assay	Homo sapiens	700.0 nM
Inhibition of human DHODH using dihydroorotate substrate at 1 uM preincubated for 30 mins followed by substrate addition by DCIP based microplate reader analysis	Homo sapiens	90.2 %
Inhibition of human DHODH using dihydroorotate substrate at 100 nM preincubated for 30 mins followed by substrate addition by DCIP based microplate reader analysis	Homo sapiens	66.8 %
Cytotoxicity against human L02 cells assessed as cell growth inhibition incubated for 96 hrs by MTT assay	Homo sapiens	486.6 nM

Cross References

Resources	Reference
ChEMBL	CHEMBL2263632
DrugBank	DB16049
FDA SRS	I58WE41H6X
PubChem	24986824
SureChEMBL	SCHEMBL355081
ZINC	ZINC000103278714

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).