L-779450 is a potent, ATP-competitiveRaf kinase inhibitor (IC50 =10 nM) that displays > 7, > 30 and > 70-fold selectivity over p38α, GSK3β and Lck respectively.
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L-779450 (L-779,450) demonstrates high specificity for Raf, with p38MAPK being the only other kinase affected due to its structurally similar kinase domain to Raf. It prevents anchorage-independent growth in human tumor lines within a dosage range of 0.3 to 2 μM[2]. The impact of L-779450 (L-779,450) on TRAIL sensitivity in melanoma cell lines is characterized by high TRAIL sensitivity (A-375 and SK-Mel-147), moderate sensitivity (Mel-HO, SK-Mel-13, and SK-Mel-28), permanent resistance (MeWo, Mel-2a, and SK-Mel-103), and acquired resistance in TRAIL-selected cell lines (A-375-TS and Mel-HO-TS). Although L-779450's direct effects on apoptosis are only moderate, it significantly boosts TRAIL-induced apoptosis in TRAIL-sensitive melanoma cells and counteracts TRAIL resistance in Mel-2a, SK-Mel-103, A-375-TS, and Mel-HO-TS, achieving 16-35% apoptosis induction at 24 hours[3].
体外研究
L-779450 (L-779,450) demonstrates high specificity for Raf, with p38MAPK being the only other kinase affected due to its structurally similar kinase domain to Raf. It prevents anchorage-independent growth in human tumor lines within a dosage range of 0.3 to 2 μM[2].
The impact of L-779450 (L-779,450) on TRAIL sensitivity in melanoma cell lines is characterized by high TRAIL sensitivity (A-375 and SK-Mel-147), moderate sensitivity (Mel-HO, SK-Mel-13, and SK-Mel-28), permanent resistance (MeWo, Mel-2a, and SK-Mel-103), and acquired resistance in TRAIL-selected cell lines (A-375-TS and Mel-HO-TS). Although L-779450's direct effects on apoptosis are only moderate, it significantly boosts TRAIL-induced apoptosis in TRAIL-sensitive melanoma cells and counteracts TRAIL resistance in Mel-2a, SK-Mel-103, A-375-TS, and Mel-HO-TS, achieving 16-35% apoptosis induction at 24 hours[3].
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