LAF389

LAF389, a prodrug of LAF153 (HY-183876), is a methionine aminopeptidase (MetAps) inhibitor with an IC₅₀ of 800 nM against MetAp2, and exhibits a maximum inhibition rate of 20% against MetAp1 at 300 nM. LAF389 possesses antiproliferative, antiangiogenic and cytotoxic activities. LAF389 can be used in research related to cancers such as advanced solid tumors^[1][2]. In Vitro:LAF389 potently inhibits monolayer proliferation of human cancer cell lines, including those unresponsive to standard cytotoxics or with drug resistance, and is more unaffected by P-glycoprotein overexpression than paclitaxel^[1].
LAF389 (0.0001-10 μM; 72 h) inhibits proliferation of HUVEC (IC₅₀ = 20 nM) and A549 human non-small cell lung carcinoma cells, with greater potency against endothelial cells and cytotoxic activity against A549 cells at micromolar concentrations^[2].
LAF389 (3-300 nM; 8-48 h) induces a pH-shifted, unprocessed form of 14-3-3γ in H1299, U2OS, MDA-MB-435, and A549 cells, with detection starting at 3 nM after 24 h and accumulation over 48 h^[2].
LAF389 (0.1-1000 nM; 18 h) inhibits processing of 14-3-3γ in HUVEC, inducing the unprocessed form with maximal response at 1 μM after 18 h of incubation^[2]. In Vivo:LAF389 exerts in vivo anti-tumor activity by inhibiting tumor cell proliferation and anti-angiogenesis, and induces transient cardiovascular effects and reversible myelosuppression in rats and dogs^[1].
LAF389 (intravenous injection; repeated bolus administration; repeated cycle 3 times with a 7-day interval after 3 consecutive days of administration) exhibits significant, frequency-dependent tumor growth inhibition in a panel of human solid tumor xenograft models in immunocompromised mice^[1].