ULK-101是一种选择性的ULK1（ IC50=1.6nM）抑制剂，还可抑制 ULK2（ IC50=30nM）的活性。
Cas No.:2443816-45-1
Sample solution is provided at 25 µL, 10mM.
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ULK-101 is a selective ULK1 inhibitor (IC₅₀=1.6nM) that inhibits ULK2 activity (IC₅₀=30nM). ULK-101 blocks cellular autophagy by inhibiting both autophagy induction and autophagic flux[1-2]. ULK-101 can be used in research related to autophagy mechanisms and cancer, particularly KRAS-mutant lung cancer[3-4].
In vitro, U2OS cells were pretreated with ULK-101 (5μM) for 2.5 hours and then stimulated with AZD8055 (100nM). ULK-101 significantly inhibited the formation of DFCP1-positive puncta and ATG12-positive phagophores. In another experiment, cells were treated with ULK-101 (5μM) for 3 hours, with BafA1 (100nM) added for the final 1.5 hours. This treatment significantly inhibited the accumulation of LC3B-positive vesicles[5]. A549, H1299, and Mv1Lu cells were pretreated with ULK-101 (1μM) for 24 hours and then stimulated with TGFβ1 (250pM). ULK-101 significantly inhibited the trafficking of cell-surface TGFβ receptors to early endosomes, late endosomes, and lysosomes. ULK-101 reduced TGFβ1-induced Smad2/Smad3 phosphorylation, nuclear translocation, expression of epithelial-mesenchymal transition (EMT) markers (N-cadherin, Slug, Snail), stress fiber formation, and cell migration[6].
In vivo, wild-type (WT) mice with house dust mite (HDM)-induced asthma were administered ULK-101 (20mg/kg) via daily intraperitoneal injection for 10 days. ULK-101 administration significantly inhibited the activation of the ULK1/Atg9a signaling pathway and reduced the expression of the NLRP3 inflammasome and its downstream effector molecules, caspase-1 and IL-1β, in lung tissues[7].
References:
[1] Hou W, Xiao C, Zhou R, et al. Inhibiting autophagy selectively prunes dysfunctional tumor vessels and optimizes the tumor immune microenvironment. Theranostics. 2025 Jan 1;15(1):258-276.
[2] Jaeger-Ruckstuhl CA, Lo Y, Fulton E, et al. Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks. Immunity. 2024 Feb 13;57(2):287-302.e12.
[3] Ikeda R, Noshiro D, Morishita H, et al. Phosphorylation of phase-separated p62 bodies by ULK1 activates a redox-independent stress response. EMBO J. 2023 Jul 17;42(14):e113349.
[4] Tian MY, Yang JQ, Hu JC, et al. Semaglutide administration protects cardiomyocytes in db/db mice via energetic improvement and mitochondrial quality control. Acta Pharmacol Sin. 2025 May;46(5):1250-1261.
[5] Martin KR, Celano SL, Solitro AR, et al. A Potent and Selective ULK1 Inhibitor Suppresses Autophagy and Sensitizes Cancer Cells to Nutrient Stress. iScience. 2018 Oct 26;8:74-84.
[6] Trelford CB, Di Guglielmo GM. Autophagy regulates transforming growth factor β signaling and receptor trafficking. Biochim Biophys Acta Mol Cell Res. 2022 Sep;1869(9):119284.
[7] Xu C, Song Y, Liu W, et al. IL-4 activates ULK1/Atg9a/Rab9 in asthma, NLRP3 inflammasomes, and Golgi fragmentation by increasing autophagy flux and mitochondrial oxidative stress. Redox Biol. 2024 May;71:103090.
ULK-101是一种选择性的ULK1（ IC50=1.6nM）抑制剂，还可抑制 ULK2（ IC50=30nM）的活性。ULK-101通过抑制自噬诱导和自噬流来阻断细胞自噬过程[1-2]。ULK-101可用于自噬机制研究和癌症（特别是KRAS突变肺癌）的相关研究[3-4]。
在体外，ULK-101（5μM）预处理U2OS细胞2.5小时，随后以AZD8055（100nM）刺激，ULK-101可显著抑制DFCP1阳性斑点和ATG12阳性吞噬斑的形成；ULK-101（5μM）处理细胞3小时，并在最后1.5小时加入BafA1（100nM），可显著抑制LC3B阳性囊泡的积累[5]。ULK-101（10μM）预处理A549、H1299及Mv1Lu细胞24小时，随后以TGFβ1（250pM）刺激。ULK-101可显著抑制细胞表面TGFβ受体向早期内体、晚期内体及溶酶体的运输，同时降低TGFβ1诱导的Smad2/Smad3磷酸化、核转位、上皮-间质转化（EMT）标记物（N-钙黏蛋白、Slug、Snail）表达、应激纤维形成及细胞迁移[6]。
在体内，ULK-101（20mg/kg）每日腹腔注射处理屋尘螨（HDM）诱导的哮喘野生型（WT）小鼠，持续10天。ULK-101可显著抑制肺组织中ULK1/Atg9a信号通路的激活，并降低NLRP3炎症小体及其下游效应分子caspase-1和IL-1β的表达[7]。
| Cell experiment [1]: | |
Cell lines | A549 cells (human non-small cell lung cancer cell line), H1299 cells (human non-small cell lung cancer cell line), and Mv1Lu cells (mink lung epithelial cell line) |
Preparation Method | A549 cells were grown in Kaighn’s Modification of Ham’s F‑12 (F‑12K) medium supplemented with 10% fetal bovine serum (FBS). H1299 cells were grown in Roswell Park Memorial Institute (RPMI) medium supplemented with 10% FBS. Mv1Lu cells were grown in Minimum Essential Medium (MEM) supplemented with 10% FBS. All cells were cultured at 37 °C under 5% CO₂, treated with ULK-101(10μM). |
Reaction Conditions | 10μM; 24h. |
Applications | ULK-101 significantly inhibited TGFβ1-induced Smad2/Smad3 phosphorylation, nuclear translocation, and the expression of epithelial–mesenchymal transition (EMT) markers (N‑cadherin, Slug, Snail). ULK-101 attenuated stress‑fiber formation and cell migration. |
| Animal experiment [2]: | |
Animal models | Wild-type (WT) and ULK1 knockout (ULK1⁻/⁻) mice (C57BL/6 background) |
Preparation Method | Mice were intranasally (i.n.) administered house dust mite (HDM) (50µg) on days 0, 7, and 14 for sensitization, and challenged daily with HDM (50µg; i.n.) on days 21-27 to induce asthma. ULK-101 (20mg/kg) was administered during the challenge phase. |
Dosage form | 20mg/kg; i.p.; daily injection for 10 days (from day 17 to day 27). |
Applications | ULK-101 administration significantly inhibited the activation of the ULK1/Atg9a signaling pathway and reduced the expression of NLRP3 inflammasome components and their downstream effectors, caspase-1 and IL-1β, in the lung tissues of HDM-induced asthmatic mice. |
References: | |
| Cas No. | 2443816-45-1 | SDF | |
| Canonical SMILES | FC1=CC=C(C(C=N2)=CN3C2=C(C4=CSC(C(N[C@@H](C5CC5)C(F)(F)F)=O)=C4)C=N3)C=C1 | ||
| 分子式 | C22H16F4N4OS | 分子量 | 460.45 |
| 溶解度 | DMSO : 83.33 mg/mL (180.98 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1718 mL | 10.8589 mL | 21.7179 mL |
| 5 mM | 434.4 μL | 2.1718 mL | 4.3436 mL |
| 10 mM | 217.2 μL | 1.0859 mL | 2.1718 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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