| 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
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
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
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as victim
Sourcing
PubMed
Sample Use Guides
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
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.
ACTIVE MOIETY
