化合物PLX8394 T3579

Product Introduction
Bioactivity


英文名: PLX8394

描述: PLX8394 是一种口服活性的丝氨酸/苏氨酸蛋白激酶 B-Raf (BRAF) 蛋白抑制剂。 PLX8394 可以选择性地结合并抑制野生型和突变形式的 BRAF 的活性，然后抑制表达 BRAF 突变形式的肿瘤细胞的增殖。 PLX8394 似乎对表达多种激酶突变形式的肿瘤有效，并且可能是对其他对 BRAF V600E 突变体特异的 BRAF 抑制剂疗法耐药的肿瘤的有效治疗剂。

细胞实验: Dissolvent: DMSO. For MTT assays, 2×103?cells are seeded in triplicate in 96 wells in their regular culture medium (containing PLX4720 for PRT lines). Next day, cells are washed twice with PBS and then the medium is replenished containing the indicated RAF inhibitor. Medium is changed 48 hours later and after a further 48 hours, 10 μL of 5 mg/mL MTT reagent is added to wells and incubated for three hours. Formazan crystals are then solubilized overnight with a 1:10 dilution of 0.1 M glycine (pH 10.5) in DMSO. Wells are then analyzed at 450 nM in a Multiskan Spectrum spectrophotometer. Results depicted are normalized to DMSO conditions and are a composite of three independent experiments. Error bars shown are representative of the standard error of mean (SEM).

动物实验: PLX8394 is dissolved in PEG 400 [20% (v/v)], TPGS [5% (v/v)], and water [75% (v/v)].H1755 tumor xenografts are generated by injection of 5×106 cells in a 50/50 mixture for matrigel and PBS into 6- to 8-wk-old female NOD/SCID mice. Mice are randomized to treatment groups once tumors reach an average size of 150 mm3. H1755 cells are s.c. implanted and allowed to grow to appr 200 mm3 (4 wk after implantation). Mice are then treated with vehicle, vemurafenib, or PLX8394 for 15 d. The vehicle for daily oral gavage is PEG 400 [20% (vol/vol)], tocopheryl polyethylene glycol succinate (TPGS) [5% (vol/vol)], water [75% (vol/vol)]. PLX8394 is dissolved in PEG 400 [20% (vol/vol)], TPGS [5% (vol/vol)], and water [75% (vol/vol)] and vortexed continuously throughout the dosing period. PLX8394 (p.o.) is given at a dose of 150 mg/kg/d.

体外活性: PLX8394 (>25 nM) effectively inhibits phosphorylation of ERK1/2 in PRT 3 and PRT 4 cells and in addition to parental cells at 10 nM. PLX8394 effectively reduces phosphorylation of retinoblastoma protein, cyclin D3/D1, and expression of cyclin A2 in parental cells and PRT 3/4 cells. PLX8394 inhibits ERK1/2 phosphorylation and the growth of vemurafenib-resistant cells harboring either a BRAF V600K/L505H double mutation or a transposon-induced, N-terminal truncated form of BRAF[1]. PLX8394 significantly impairs tumor cell growth and suppresses MAPK signaling in LA cell lines expressing either endogenous V600E or non-V600 mutant forms of BRAF[2].

体内活性: In mice H1755 xenograft tumors, PLX8394 (150 mg/kg/day) substantially suppresses tumor growth, tumor cell proliferation and MAPK pathway signaling without overt toxicity. PLX8394 combines with erlotinib yields plasma erlotinib concentrations of >1 μM[2].

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 50 mg/mL (92.16 mM)


关键字: PLX-8394 | PLX 8394 | PLX8394

相关产品: TAK-632 | GSK1904529A | GNE-9815 | Raf inhibitor 1 | GW 5074 | TAK-580 | AZ304 | Effusanin A | K-Ras-IN-1 | Encorafenib

相关库: Drug Repurposing Compound Library | HIF-1 Signaling Pathway Compound Library | Anti-Cancer Drug Library | Kinase Inhibitor Library | Anti-Cancer Clinical Compound Library | Inhibitor Library | Anti-Obesity Compound Library | Anti-Cancer Active Compound Library | Tyrosine Kinase Inhibitor Library | Hematonosis Compound Library

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注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途