FIBOFLAPON

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Search structure


Synonyms	AM-803 Am803 Fiboflapon GSK-2190915 GSK2190915 GSK2190915B
Status
Molecule Category	UNKNOWN
UNII	Y1NA96IX3T
EPA CompTox	DTXSID20239496


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

Structure


InChI Key	DFQGDHBGRSTTHX-UHFFFAOYSA-N
Smiles	CCOc1ccc(-c2ccc(Cn3c(CC(C)(C)C(=O)O)c(SC(C)(C)C)c4cc(OCc5ccc(C)cn5)ccc43)cc2)cn1
InChI	InChI=1S/C38H43N3O4S/c1-8-44-34-18-14-28(22-40-34)27-12-10-26(11-13-27)23-41-32-17-16-30(45-24-29-15-9-25(2)21-39-29)19-31(32)35(46-37(3,4)5)33(41)20-38(6,7)36(42)43/h9-19,21-22H,8,20,23-24H2,1-7H3,(H,42,43)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C38H43N3O4S
Molecular Weight	637.85
AlogP	8.98
Hydrogen Bond Acceptor	7.0
Hydrogen Bond Donor	1.0
Number of Rotational Bond	12.0
Polar Surface Area	86.47
Molecular species	ACID
Aromatic Rings	5.0
Heavy Atoms	46.0

Bioactivity

Mechanism of Action	Action	Reference
5-lipoxygenase activating protein inhibitor	INHIBITOR	PubMed PubMed


Protein: 5-lipoxygenase activating protein Description: Arachidonate 5-lipoxygenase-activating protein Organism : Homo sapiens P20292 ENSG00000132965

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Lyase	-	36000	-	-	-
Enzyme Oxidoreductase	-	20000	-	-	-
Other cytosolic protein	-	1-506	-	-	-

Assay Description	Organism	Bioactivity	Reference
Displacement of [3H]-3-[5-(pyrid-2-ylmethoxy)-3-tert-butylthio-1-benzylindol-2-yl]-2,2-dimethylpropionic acid from FLAP in human polymorphonuclear cell membranes after 1 hr by scintillation counting	Homo sapiens	2.9 nM
Inhibition of FLAP in rat whole blood assessed as inhibition of calcium ionophore A23187-induced LTB4 production preincubated for 15 mins by ELISA	Rattus norvegicus	239.0 nM
Inhibition of FLAP in rat whole blood assessed as inhibition of calcium ionophore A23187-induced LTB4 production preincubated for 4 hrs by ELISA	Rattus norvegicus	16.0 nM
Inhibition of FLAP in human whole blood assessed as inhibition of calcium ionophore A23187-induced LTB4 production preincubated for 15 mins by ELISA	Homo sapiens	506.0 nM
Inhibition of FLAP in human whole blood assessed as inhibition of calcium ionophore A23187-induced LTB4 production preincubated for 5 hrs by ELISA	Homo sapiens	76.0 nM
Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	Homo sapiens	0.7 nM
Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 5 mins by ELISA in absence of human serum albumin	Homo sapiens	1.0 nM
Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 1 hr by ELISA in absence of human serum albumin	Homo sapiens	1.0 nM
Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA in presence of 0.5% human serum albumin	Homo sapiens	26.0 nM
Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 3 hr by ELISA in presence of 0.5% human serum albumin	Homo sapiens	4.0 nM
Inhibition of human CYP3A4	Homo sapiens	50.0 nM
Inhibition of human CYP2C9	Homo sapiens	50.0 nM
Binding Assay: Compound 2 was examined for its ability to bind human FLAP using a membrane-binding assay. The affinity of Compound 2 for human FLAP was assessed using membranes from human polymorphonuclear leukocytes and tritiated leukotriene synthesis inhibitor, 3H-3-[5-(pyrid-2-ylmethoxy)-3-tert-butylthio-1-benzyl-indol-2-yl]-2,2-dimethylpropionic acid, as a ligand. A non-limiting example of such a FLAP binding assay is as follows: Packed human polymorphonuclear cell pellets (1.8x109 cells) (Biological Speciality Corporation) were resuspended, lysed and 100,000 g membranes prepared as described (Charleson et al. Mol. Pharmacol, 41, 873-879, 1992). 100,000 g pelleted membranes were resuspended in Tris-Tween assay buffer (100 mM Tris HCl pH 7.4, 140 mM NaCl, 2 mM EDTA, 0.5 mM DTT, 5% glycerol, 0.05% Tween 20) to yield a protein concentration of 50-100 ug/mL.	Homo sapiens	2.9 nM

Cross References

Resources	Reference
ChEMBL	CHEMBL1922660
DrugBank	DB06346
FDA SRS	Y1NA96IX3T
PubChem	44473151
SureChEMBL	SCHEMBL11820
ZINC	ZINC000068247071

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).