Tolinapant (ASTX660)

製品コードS8681 バッチS868101

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₃₀H₄₂FN₅O₃

分子量

539.68

CAS No.

1799328-86-1

Solubility (25°C)*

体外

DMSO

100 mg/mL (185.29 mM)

Ethanol

100 mg/mL (185.29 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	5% DMSO 1 95% Corn oil	0.625mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 12.5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	5.0mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 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	Tolinapant (ASTX660) is a potent, non-peptidomimetic antagonist of cIAP1/2 and XIAP that inhibits the interactions between a SMAC-derived peptide and the BIR3 domains of XIAP (BIR3-XIAP) and cIAP1 (BIR3-cIAP1) with IC50 values less than 40 and 12 nmol/L, respectively.
in vitro	ASTX660 induces proteasomal degradation of cIAP1 and 2, resulting in downstream effects of NIK stabilization and activation of noncanonical NF-kB signaling, demonstrating cIAP1/2 antagonism. Because of their roles in the evasion of apoptosis, inhibitor of apoptosis proteins (IAP) are considered attractive targets for anticancer therapy. Treatment with ASTX660 leads to TNFa-dependent induction of apoptosis in various cancer cell lines in vitro.^[1]
in vivo	ASTX660 is orally bioavailable in mice and demonstrates prolonged antagonism of XIAP and cIAP1 in vivo. ASTX660 dosing in mice bearing breast and melanoma tumor xenografts causes growth inhibition of MDA-MB-231 and A375 xenograft tumors in vivo.^[1]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	MDA-MB-231, HEK293, A375, SK-MEL-28, WSU-DLCL2
	濃度	1 nM - 10 μM
	反応時間	5 min - 4 h
	実験の流れ	Live cell imaging. Cells are incubated with ASTX660 in 0.1% (v/v) DMSO, with or without neutralizing anti-TNFa antibody for 5 days, and live images are taken every 3 hours using a 10× objective.
動物実験	動物モデル	male BALB/c wild type mice, male SCID mice with MDA-MB-231 xenografts, male nude mice with A375 xenografts
	投薬量	5, 10, 20 mg/kg
	投与方法	Oral gavage

参考

[1] Ward GA, et al. Mol Cancer Ther. 2018 Jul;17(7):1381-1391.

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：

Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer [ Heliyon, 2023, 9(10):e20655]	PubMed: 37867861
Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer [ Heliyon, 2023, 9(10):e20655]	PubMed: 37867861
Novel smac mimetic ASTX660 (Tolinapant) and TNF-α synergistically induce necroptosis in bladder cancer cells in vitro upon apoptosis inhibition [ Biochem Biophys Res Commun, 2022, 602:8-14]	PubMed: 35247703

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。