Inhibitor dehydrogenazy metylenotetrahydrofolianowej 1/2 (MTHFD1/2), który wykazuje skuteczność przeciwnowotworową in vitro i in vivo poprzez ukierunkowanie na cykl folianowy.
LY345899 (LY354899) jest inhibitorem dehydrogenazy metylenotetrahydrofolianowej (MTHFD1 IC50 = 96 nM z 30 μM folitiksoryny i 400 μM NADP+; MTHFD2 IC50 = 663 nM z 5 μM folitiksoryny i 250 μM NAD+), który wywiera działanie antyproliferacyjne przeciwko komórkom nowotworowym poprzez ukierunkowanie na cykl folianowy. Jednoczesne podawanie LY345899 z inhibitorem reduktazy dihydrofolianowej (DHFR) metotreksatem (MTX) przezwycięża oporność AML na MTX (50 mg/kg) u myszy in vivo (10 mg/kg q.o.d. i.p.).
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The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in
The Journal of pharmacology and experimental therapeutics, 287(1), 315-321 (1998-10-09)
5,6,7,8-Tetrahydro-N5,N10-carbonylfolic acid (LY354899) has been demonstrated to inhibit the dehydrogenase activity of C1-tetrahydrofolate synthase. This compound was only moderately antiproliferative toward CCRF-CEM lymphocytic leukemia cells in culture, but induced apoptosis after long incubation times. Slightly greater potency was observed in
Metabolic reprogramming by oncogenic signaling is a hallmark of cancer. Hyperactivation of Wnt/β-catenin signaling has been reported in hepatocellular carcinoma (HCC). However, the mechanisms inducing hyperactivation of Wnt/β-catenin signaling and strategies for targeting this pathway are incompletely understood. In this
Journal of the National Cancer Institute, 111(6), 584-596 (2018-12-12)
Overcoming oxidative stress is a critical step for tumor progression; however, the underlying mechanisms in colorectal cancer (CRC) remain unclear. We investigated nicotinamide adenine dinucleotide (phosphate) (NAD(P))-dependent enzyme methylene tetrahydrofolate dehydrogenase 2 (MTHFD2) expression, clinical relevance, redox modification, and molecular
Nasz zespół naukowców ma doświadczenie we wszystkich obszarach badań, w tym w naukach przyrodniczych, materiałoznawstwie, syntezie chemicznej, chromatografii, analityce i wielu innych dziedzinach.
