VELIFLAPON

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H23NO3
Molecular Weight	361.4336
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)[C@H](C1CCCC1)C2=CC=C(OCC3=CC=C4C=CC=CC4=N3)C=C2

InChI

InChIKey=ZEYYDOLCHFETHQ-JOCHJYFZSA-N

InChI=1S/C23H23NO3/c25-23(26)22(17-6-1-2-7-17)18-10-13-20(14-11-18)27-15-19-12-9-16-5-3-4-8-21(16)24-19/h3-5,8-14,17,22H,1-2,6-7,15H2,(H,25,26)/t22-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C23H23NO3
Molecular Weight	361.4336
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8213345 | https://www.decode.com/decode-initiates-phase-iii-trial-for-dg031-for-the-prevention-of-heart-attack/

Veliflapon (BAY X1005, DG-031) is an enantioselective inhibitor of 5-lipoxygenase activating protein, or FLAP. There are variants in the gene encoding FLAP, and the gene encoding leukotriene A4 hydrolase (LTA4H) linked to risk of heart attack. These variants appear to confer increased risk of heart attack by increasing the production of leukotriene B4 (LTB4), a potent driver of inflammation produced in atherosclerotic plaques. deCODE licensed veliflapon (BAY X1005, DG-031) from Bayer AG, which developed it originally for the treatment of asthma.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
5-lipoxygenase activating protein 7 Target ID: CHEMBL4550 Sources: https://www.decode.com/decode-initiates-phase-iii-trial-for-dg031-for-the-prevention-of-heart-attack/	Inhibitor 8504		0.165 µM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute coronary syndrome 33 Sources: https://www.decode.com/decode-initiates-phase-iii-trial-for-dg031-for-the-prevention-of-heart-attack/	Preventing		Phase III 665	VELIFLAPON Approved Use Unknown
Asthma 244 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15886380	Primary		Phase III 665	VELIFLAPON Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
5.82 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8844447/	250 mg 2 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VELIFLAPON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
11 μg/mL PATENT https://patents.google.com/patent/US20060257481A1	250 mg 3 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		VELIFLAPON plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
35.3 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8844447/	250 mg 2 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VELIFLAPON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.5 h PATENT https://patents.google.com/patent/US20060257481A1	250 mg 3 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		VELIFLAPON plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 2052

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=137275911	no

Sourcing

Vendor/Aggregator	ID	URL
ApexBio Technology	B5447	https://www.apexbt.com/catalogsearch/result/?q=B5447
BOC Sciences	128253-31-6	http://www.bocsci.com/description.asp?cas=128253-31-6
Chem Scene	CS-0003243	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0003243
eMolecules	36500816	https://orderbb.emolecules.com/search/#?query=36500816
mcule	MCULE-5863120755	https://mcule.com/MCULE-5863120755/
MedChem Express	HY-14165	https://www.medchemexpress.com/search.html?q=HY-14165&ft=&fa=&fp=
MolPort	MolPort-023-276-843	https://www.molport.com/shop/molecule-link/MolPort-023-276-843
MuseChem	M117956	https://www.musechem.com/product/M117956.html
Tocris	3541	https://www.tocris.com/search.php?Type=QuickSearch&Value=3541

PubMed

Title	Date	PubMed
5-Lipoxygenase-activating protein (FLAP) inhibitors. Part 4: development of 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid (AM803), a potent, oral, once daily FLAP inhibitor.	2011-12-08	22059882
Inhibition of 5-lipoxygenase-activating protein abrogates experimental liver injury: role of Kupffer cells.	2005-10	16033810
Interactions among three classes of mediators explain antigen-induced bronchoconstriction in the isolated perfused and ventilated guinea pig lung.	2003-10	12954791
Inhibition of 5-lipoxygenase induces cell growth arrest and apoptosis in rat Kupffer cells: implications for liver fibrosis.	2003-09	12958196
Inhibition of 5-lipoxygenase activating protein decreases proteinuria in diabetic rats.	2002-09-17	12649539
Leukotriene C4 is a tight-binding inhibitor of microsomal glutathione transferase-1. Effects of leukotriene pathway modifiers.	1999-01-22	9890956
Pharmacological modulation of human platelet leukotriene C4-synthase.	1997-03-21	9113110
Mode of action of the new selective leukotriene synthesis inhibitor BAY X 1005 ((R)-2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl acetic acid) and structurally related compounds.	1993-01-07	8381000
Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis.	1990-01-18	2300173

Patents

Sample Use Guides

In Vivo Use Guide

Patients randomized into 6 treatment sequences; a sequence with DG-031 first and then placebo and a sequence with placebo first and then DG-031 for each of the 3 dosages: 250 mg/d, 500 mg/d, and 750 mg/d. All patients received 3 tablets per day.

Route of Administration: Oral

In Vitro Use Guide

Veliflapon (BAY X1005) effectively inhibits the synthesis of leukotriene B4 (LTB4) in A23187-stimulated leukocytes from rats, mice and humans (IC50 0.026, 0.039 and 0.22 uM, respectively), as well as the formation of leukotriene C4 (IC50 0.021 uM) in mouse peritoneal macrophages stimulated with opsonized zymosan. The compound is, however, less active in inhibiting LTB4 synthesis in human whole blood (IC50 17.0 and 11.6 uM, as measured by RIA or HPLC, respectively). BAY X1005 is shown to be a selective inhibitor of the formation of 5-lipoxygenase-derived metabolites in vitro, without effects on other routes of arachidonic acid metabolism such as 12-lipoxygenase in human whole blood and cyclooxygenase in both mouse macrophages and human whole blood. BAY X1005 is devoid of any antioxidant activity (methemoglobin induction and xanthine-xanthine oxidase assay), without effects on granule release and with only weak effects on reactive oxygen species generation in human polymorphonuclear leukocytes.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 07:05:10 GMT 2025` Edited by `admin` on `Wed Apr 02 07:05:10 GMT 2025`
Record UNII	JXH6X663L0
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VELIFLAPON

Official Name

English

BAY X 1005

Preferred Name

English

DG-031

Code

English

BAY X-1005

Code

English

veliflapon [INN]

Common Name

English

BAY-X-1005

Code

English

(+)-(2R)-CYCLOPENTYL(QUINOLIN-2-YLMETHOXY)ACETIC ACID

Systematic Name

English

BENZENEACETIC ACID, .ALPHA.-CYCLOPENTYL-4-(2-QUINOLINYLMETHOXY)-, (.ALPHA.R)-

Common Name

English

VELIFLAPON [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C78274