(3S)-N-[5-[(2R)-2-(2,5-二氟苯基)-1-吡咯烷基]吡唑并[1,5-a]嘧啶-3-基]-3-羟基-1-吡咯烷甲酰胺硫酸盐

商品名称 
CAS号 1223405-08-0
分子式 C21H24F2N6O6S
分子量 526.51400
LogP 3.45140
PSA 168.98000
产品描述:loxo-101 is a small molecule that was designed to block the atp binding site of the trk family of receptors, with 2 to 20 nm cellular potency against the trka, trkb, and trkc kinases. ic50 value: 2 - 20 nm target: trka/b/c in vitro: loxo-101 is an orally administered inhibitor of the trk kinase and is highly selective only for the trk family of receptors. loxo-101 is evaluated for off-target kinase enzyme inhibition against a panel of 226 non-trk kinases at a compound concentration of 1,000 nm and atp concentrations near the km for each enzyme. in the panel, loxo-101 demonstrates greater than 50% inhibition for only one non-trk kinase (tnk2 ic50, 576 nm). measurement of proliferation following treatment with loxo-101 demonstrates a dose-dependent inhibition of cell proliferation in all three cell lines. the ic50 is less than 100 nm for cuto-3.29 and less than 10 nm for km12 and mo-91, consistent with the known potency of this drug for the trk kinase family. [1] loxo-101 demonstrates potent and highly-selective inhibition of trka, trkb, and trkc over other kinase- and non-kinase targets. loxo-101 is a potent, atp-competitive trk inhibitor with ic50s in low nanomolar range for inhibition of all trk family members in binding and cellular assays, with 100x selectivity over other kinases. [2] in vivo: athymic nude mice injected with km12 cells are treated with loxo-101 orally daily for 2 weeks. dose-dependent tumor inhibition is observed, demonstrating the ability of this selective compound to inhibit tumor growth in vivo.