5.31091

Porcn Inhibitor IV, LGK974

• 別名: Porcn Inhibitor IV, LGK974, 2-(2ʹ,3-Dimethyl-2,4ʹ-bipyridin-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide, Wnt Pathway Inhibitor XXIII, LGK-974
• 実験式（ヒル表記法）: C₂₃H₂₀N₆O
• CAS番号: 1243244-14-5
• 分子量: 396.44
• MDL番号: MFCD27501026
• UNSPSCコード: 12352200
• NACRES: NA.77

特性

• アッセイ: ≥97% (HPLC)
• 品質水準: 100
• フォーム: powder
• メーカー／製品名: Calbiochem^®
• 保管条件: OK to freeze; protect from light
• 色: tan
• 溶解性: DMSO: 50 mg/mL
• 保管温度: 2-8°C
• SMILES記法: N(c3ncc(cc3)c4nccnc4)C(=O)Cc1cnc(c(c1)C)c2cc(ncc2)C
• InChI: 1S/C23H20N6O/c1-15-9-17(12-28-23(15)18-5-6-25-16(2)10-18)11-22(30)29-21-4-3-19(13-27-21)20-14-24-7-8-26-20/h3-10,12-14H,11H2,1-2H3,(H,27,29,30)
• InChI Key: XXYGTCZJJLTAGH-UHFFFAOYSA-N

詳細

詳細

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 (IC₅₀ from 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 µM. 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.

生物化学的／生理学的作用

Cell permeable: yes

Primary Target
Porcupine

Reversible: yes

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

再構成

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

その他情報

Liu, J., et al. 2013. Proc. Natl. Acad. Sci. USA110, 20224.

法的情報

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

安全性情報

• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 3
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable