半岛bd体育手机客户端 说明
一般描述
A cell-permeable C59 (Cat. No. 500496) structural analog that potently inhibits Wnt secretion from L-cell Wnt1/2/3/3a/6/7a/9a transfectants (IC50from 50 pM to 1.1 nM) via direct porcupine (Porcn), but not Wntless, affinity interaction. Shown to inhibit the proliferation of head and neck squamous cell carcinoma (HNSCC) line HN30 (IC50= 0.3 nM), but not 293T even at a high concentration of 20 ?M. In mice & rats receiving therapeutic LGK974 oral dosages (up to 5 mg/10 mL/kg/d), a delayed tissue Wnt signaling suppression (max inhibition 7 to 10 h post dosing) is seen due to pre-existing Wnt in tissue, followed by a full recovery of tissue Wnt signalling at 24 h upon drug clearance. The periodic daily inhibition/recovering cycle is shown to result in tumor regression in mice & rats, while allowing Wnt signaling-dependent normal tissue homeostasis. Overdosing is reported to result in loss of intestinal epithelium in rats receiving 14 consecutive 20 mg/kg daily oral dosages.
A cell-permeable C59 (Cat. No. 500496) structural analog that potently inhibits TM3 cellular Wnt pathway activation-dependent transcription by blocking Wnt secretion from co-cultured L-cells (IC50from 50 pM to 1.1 nM using Wnt1/2/3/3a/6/7a/9a L-cell transfectants) via direct porcupine (Porcn), but not Wntless, affinity interaction. Shown to inhibit Wnt-dependent proliferation of head and neck squamous cell carcinoma (HNSCC) line HN30 (IC50= 0.3 nM in 48 h colony formation assay), but not the growth of 293T even at concentrations as high as 20 ?M. In mice & rats receiving therapeutic LGK974 oral dosages (up to 5 mg/10 mL/kg/d), a delayed tissue Wnt signaling suppression (max inhibition 7 to 10 h post dosing) is seen due to pre-existing Wnt in tissue, followed by a full recovery of tissue Wnt signalling at 24 h upon drug clearance. The periodic daily inhibition/recovering cycle is shown to result in tumor regression in mice & rats harboring tumors derived from human HNSCC HN30 or tumor fragments from murine mammary tumor virus (MMTV)-Wnt1 transgenic mice, while allowing Wnt signaling-dependent normal tissue homeostasis. Overdosing is reported to result in loss of intestinal epithelium in rats receiving 14 consecutive 20 mg/kg daily oral dosages.
生化/生理作用
Cell permeable: yes
Primary Target
Porcupine
Reversible: yes
包装
Packaged under inert gas
警告
Toxicity: Standard Handling (A)
重悬
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
其他说明
Liu, J., et al. 2013.Proc. Natl. Acad. Sci. USA110,20224.
法律信息
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
基本信息
经验(实验)分子式 | C23H20N6O |
分子量 | 396.44 |
半岛bd体育手机客户端 性质
质量水平 | 100 |
测定 | ≥97% (HPLC) |
形式 | powder |
manufacturer/tradename | Calbiochem? |
储存条件 | OK to freeze protect from light |
颜色 | tan |
溶解性 | DMSO: 50 mg/mL |
储存温度 | 2-8℃ |
安全信息
储存分类代码 | 11 - Combustible Solids |
WGK | WGK 3 |
闪点(F) | Not applicable |
闪点(C) | Not applicable |
Sigma-Aldrich