AD80

製品コードS8518 バッチS851801

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22H19F4N7O
分子量 473.43 CAS No. 1384071-99-1
Solubility (25°C)* 体外 DMSO 94 mg/mL (198.55 mM)
Ethanol 94 mg/mL (198.55 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
2%DMSO 30%PEG300 2%Tween80 66%ddH2O
4.0mg/ml Taking the 1 mL working solution as an example, add 20 μL of 200 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 660 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 AD80, a multikinase inhibitor, shows strong activity against human RET (c-RET), BRAF, S6K, and SRC but were much less active than either AD57 or AD58 against mTOR. The IC50 value for RET is 4 nM.
in vitro AD80 prevents the phosphorylation of RET as well as of extracellular signa-regulated kinase (ERK), AKT, and S6K at low nanomolar concentrations in kinesin family member 5B (KIF5B)-RET-expressing Ba/F3 cells. Treatment with AD80 results in up-regulation of genes that are typically repressed by active KRAS. On the contrary, genes that are activated by KRAS were down-regulated[1]. On the basis of in vitro human kinase profiles, AD80 and AD81 inhibit RET, RAF, SRC and S6K, with greatly reduced mTOR activity relative to AD57 and AD58. AD80 inhibits proliferation of MZ-CRC-1 and TT thyroid cancer cells in culture, probably through the induction of apoptosis[2].
in vivo AD80 is a highly potent RET inhibitor with a favorable pharmacokinetic profile in clinically relevant RET fusion-driven tumor models. AD80 potently shrinks RET-rearranged tumors in patient-derived xenografts. A pronounced reduction in phosphorylation of RET as well as AKT and ERK in tumors treated with AD80 (25 mg/kg) is observed but not in tumors treated with cabozantinib or vandetanib[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 LC-2/AD cells
濃度 0, 10, or 100 nM
反応時間 4 h
実験の流れ

Immunoblotting is performed in LC-2/AD cells treated with AD80, cabozantinib, or vandetanib (4 hours).
動物実験 動物モデル NSG mice
投薬量 12.5 to 25 mg/kg 
投与方法 oral gavage

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Distinctive molecular features of regenerative stem cells in the damaged male germline [ Nat Commun, 2022, 13(1):2500] PubMed: 35523793
Targeting RET Kinase in Neuroendocrine Prostate Cancer [ Mol Cancer Res, 2020, 18(8):1176-1188] PubMed: 32461304
Elucidating the Mechanism of RET Kinase Activity in Neuroendocrine Prostate Cancer [ Mol Cancer Res, 2020, 1176-1188] PubMed: None
Targeting RET Kinase in Neuroendocrine Prostate Cancer [ Mol Cancer Res, 2020, 27;molcanres.1245.2019] PubMed: 32461304
Neurturin regulates the lung-resident macrophage inflammatory response to viral infection [ Life Sci Alliance, 2020, 3(12)e202000780] PubMed: 33020210
RET Kinase Signaling as a Key Switch Toward the Neuroendocrine Phenotype [ Defense Technical Information Center, 2020, N/A] PubMed: N/A
Multi-kinase targeted therapy as a promising treatment strategy for ovarian tumors expressing sfRon receptor [ Genes Cancer, 2020, 11(3-4):106-121] PubMed: 33488949
[ Cell Rep, 2017, ] PubMed: 28877471

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。