FLAP Inhibitor

MK-886 (L 663536) is a potent, cell-permeable and orally active FLAP (IC₅₀ of 30 nM) and leukotriene biosynthesis (IC₅₀s of 3 nM and 1.1 μM in intact leukocytes and human whole blood, respectively) inhibitor. MK-886 is also a non-competitive PPARα antagonist and can induce apoptosis.

FEN1-IN-1 (compound 1) is a small molecule flap endonuclease 1 (FEN1) inhibitor with antitumor activity. FEN1-IN-1 binds to the active site of FEN1 and partly achieves inhibition by the co-ordination of Mg²⁺ ions. FEN1-IN-1 initiaties a DNA damage response and activates the ATM checkpoint signalling pathway, the phosphorylation of histone H2AX and the ubiquitination of FANCD2 in mammalian cells. FEN1-IN-1 is promising for research of cancers.

Quiflapon (MK-591) is a selective and specific 5-lipoxygenase-activating protein (FLAP) inhibitor with an IC₅₀ of 1.6 nM in a FLAP binding assay. Quiflapon is also a potent and orally active Leukotriene biosynthesis (LT) inhibitor, shows IC₅₀ values of 3.1 and 6.1 nM in intact human and elicited rat PMNLs, respectively. Quiflapon induces cell apoptosis.

FEN1-IN-4 (Compound 2) is a human flap endonuclease-1 (hFEN1) inhibitor.

Fiboflapon (GSK2190915; AM-803) is a potent and orally bioavailable 5-lipoxygenase-activating protein (FLAP) inhibitor with a potency of 2.9 nM in FLAP binding, an IC₅₀ of 76 nM for inhibition of LTB4 in human blood.

AM-643 is a FLAP inhibitor with human IC₅₀ of 2 nM, oral activity, and dermal activity.AM-643 selectively inhibits FLAP, reduces leukotriene biosynthesis and reduces inflammatory ear swelling.AM-643 can be used for the research of skin disorders involving leukotriene production.

FEN1-IN-9 is a selective flap endonuclease 1 (FEN1) inhibitor with an IC₅₀ of 37.9 μM. FEN1-IN-9 can be used for the research of DNA damage repair.

Quiflapon sodium (MK-591 sodium) is a selective and specific 5-Lipoxygenase-activating protein (FLAP) inhibitor. Quiflapon sodium is an orally active Leukotriene biosynthesis inhibitor. Induces apoptosis.

FEN1-IN-2 (compound 20) is a flap endonuclease 1 (FEN1) inhibitor, with IC50 values of 3 nM and 226 nM for FEN1 and XPG, respectively.

Atuliflapon (AZD5718) is an orally active inhibitor of FLAP (5?Lipoxygenase activating protein), with an IC₅₀ of 2 nM. Atuliflapon is used in the study for coronary artery disease.

Diflapolin is a highly active dual 5-lipoxygenase-activating protein (FLAP)/soluble epoxide hydrolase (sEH) inhibitor with marked anti-inflammatory efficacy and high target selectivity. Diflapolin inhibits 5-LOX product formation in intact human monocytes and neutrophils with IC₅₀s?of? 30 and 170?nM, respectively, and suppressed the activity of isolated sEH (IC₅₀=20?nM).

MSC778 is an effective and orally active flap endonuclease 1 (FEN1) inhibitor with an IC₅₀ of 3 nM and a K_D of 2.9 nM. MSC778 exhibits 145-fold, 516-fold, and 65-fold selectivity over EXO1, GEN1, and XPG, respectively. MSC778 selectively kills BRCA2-deficient cells and potentiates the activity of Niraparib (HY-10619) to induce tumor stasis in a BRCA2 KO DLD-1 mouse xenograft. MSC778 can be used in the research of colorectal cancer.

AM679 is a potent, selective 5-lipoxygenase-activating protein (FLAP) inhibitor with an IC₅₀ of 2 nM in a human FLAP membrane binding assay. AM679 markedly reduces the respiratory syncytial virus-driven ocular pathology as well as the synthesis of cysteinyl leukotrienes (CysLTs) in the eye.

Fiboflapon sodium (GSK2190915; AM-803) is a potent and orally bioavailable 5-lipoxygenase-activating protein (FLAP) inhibitor with a potency of 2.9 nM in FLAP binding, an IC₅₀ of 76 nM for inhibition of LTB4 in human blood.

FEN1-IN-7 (compound 16) is a selective inhibitor of Flap endonuclease-1 (FEN1, IC₅₀=18 nM), involving in mammalian cells to repair DNA damage. FEN1-IN-7 also targets to related endonuclease, xeroderma pigmentosum G (XPG) with an IC₅₀ value of 3.04 μM. FEN1-IN-7 increases the cellular sensitivity of cancer cells to potent DNA alkylating agents or methylating agents.

Veliflapon (BAY X 1005; DG-031) is an orally active and selective 5-lipoxygenase activating protein (FLAP) inhibitor. Veliflapon inhibits the synthesis of the leukotrienes B4 and C4.

FEN1-IN-5 (compound 12A) is a potent inhibitor of Flap endonuclease-1 (FEN1, IC₅₀=12 nM), involving in DNA repair.

(S)-Veliflapon ((S)-BAY X 1005) is an orally active inhibitor of leukotriene biosynthesis and 5-lipoxygenase activating protein (FLAP). (S)-Veliflapon inhibits the formation of leukotriene B4 (LTB4) in rat, mouse and human leukocytes with IC₅₀ values of 0.026 µM, 0.039 µM and 0.22 µM respectively. (S)-Veliflapon showes enantioselectivity in human whole blood.

FEN1-IN-6 (compound 9) is a potent inhibitor of Flap endonuclease-1 (FEN1, IC₅₀=10 nM), involving in mammalian cells to repair DNA damage. FEN1-IN-6 also targets to related endonuclease, xeroderma pigmentosum G (XPG) with an IC₅₀ value of 23 nM.

FEN1-IN-3 (Compound 4) is a human flap endonuclease-1 (hFEN1) inhibitor. FEN1-IN-3 stabilizes hFEN1 with an EC₅₀ of 6.8 μM.