SBI-0206965
目录号 : GC15654
SBI-0206965，这种嘧啶衍生物是一种高选择性的激酶ULK1抑制剂，IC50值为108nM。
Cas No.:1884220-36-3
Sample solution is provided at 25 µL, 10mM.
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SBI-0206965 , the pyrimidine derivative , is a highly selective kinase ULK1 inhibitor with an IC50 value of 108nM[1]. SBI-0206965 was reported as a small-molecule inhibitor of kinase ULK2 , which has an IC50 value as 711nM[2]. SBI-0206965 can also inhibit AMPK[3].
SBI-0206965 (25μM , 3h) modestly inhibited AMPK signalling in C2C12 myotubes, but also inhibited Insulin signalling , Insulin-mediated/AMPK-independent glucose uptake[4]. SBI-0206965 (10μM , 40min) has a non-specific off-target inhibitory effect on muscle glucose transport[2]. SBI-0206965 ( 8μmol/L , 1h) reversed hypoxia/reoxygenation (H/R)-induced cell death and pyroptosis in cardiomyocytes[5] .
SBI-0206965 (50mg/kg ; 3 days , 9 times in 30 days ; intraperitoneal injection) triggered apoptosis by preventing autophagy and pentose phosphate pathway (PPP) flux[6] . SBI-0206965 ( 5 or 50μM ; 2.5h ; intravitreal injections , optic nerve live imaging) protects against acute axonal degeneration (AAD) after rat optic nerve crush in vivo[7] .
SBI-0206965 suppressed 5-aminoimidazole-4-carboxamideribo nucleotide(AICAR) stimulated glucose transport in both the extensor digitorum longus and soleus muscle [2] .
References:
[1] CHEN Y, XIE X, WANG C, et al. Dual targeting of NUAK1 and ULK1 using the multitargeted inhibitor MRT68921 exerts potent antitumor activities [J]. Cell Death Dis, 2020, 11(8): 712.
[2] KNUDSEN J R, MADSEN A B, PERSSON K W, et al. The ULK1/2 and AMPK Inhibitor SBI-0206965 Blocks AICAR and Insulin-Stimulated Glucose Transport [J]. Int J Mol Sci, 2020, 21(7):
[3] DITE T A, LANGENDORF C G, HOQUE A, et al. AMP-activated protein kinase selectively inhibited by the type II inhibitor SBI-0206965 [J]. J Biol Chem, 2018, 293(23): 8874-85.
[4] AHWAZI D, NEOPANE K, MARKBY G R, et al. Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965 [J]. Biochem J, 2021, 478(15): 2977-97.
[5] DENG L, JIANG L, WEI N, et al. Anesthetic sevoflurane simultaneously regulates autophagic flux and pyroptotic cell death-associated cellular inflammation in the hypoxic/re-oxygenated cardiomyocytes: Identification of sevoflurane as putative drug for the treatment of myocardial ischemia-reperfusion injury [J]. Eur J Pharmacol, 2022, 936(175363.
[6] LU J, ZHU L, ZHENG L P, et al. Overexpression of ULK1 Represents a Potential Diagnostic Marker for Clear Cell Renal Carcinoma and the Antitumor Effects of SBI-0206965 [J]. EBioMedicine, 2018, 34(85-93.
[7] VAHSEN B F, RIBAS V T, SUNDERMEYER J, et al. Inhibition of the autophagic protein ULK1 attenuates axonal degeneration in vitro and in vivo, enhances translation, and modulates splicing [J]. Cell Death Differ, 2020, 27(10): 2810-27.
SBI-0206965，这种嘧啶衍生物是一种高选择性的激酶ULK1抑制剂，IC50值为108nM[1]。SBI-0206965亦是ULK2激酶的小分子抑制剂，IC50值为711nM[2]。SBI-0206965也能抑制AMPK[3]。
SBI-0206965（25μM，3小时）适度抑制C2C12肌管中的AMPK信号传导，但也抑制胰岛素信号传导、胰岛素介导/与AMPK无关的葡萄糖摄取[4]。SBI-0206965（10μM，40分钟）对肌肉葡萄糖转运具有非特异性脱靶抑制作用[2]。
SBI-0206965（8μmol/L，1小时）可逆转缺氧/再氧化（H/R）诱导的心肌细胞死亡和焦亡[5]。SBI-0206965(50毫克/公斤；3天，30天9次；腹腔注射)通过阻止自噬和戊糖磷酸途径（PPP）进行而引发细胞凋亡[6]。SBI-0206965(5或50μM；2.5小时；玻璃体内注射（视神经实时成像）对视神经挤压后急性轴突变性（AAD）的体内保护作用[7]。
SBI-0206965抑制了伸趾长肌和腓肠肌中5-氨基咪唑-4-羧酰胺核糖核苷酸（AICAR）刺激的葡萄糖转运[2]。
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Cell experiment[1]: |
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Cell lines |
Murine embryonic fibroblast cells ( soleus and extensor digitorum longus muscles) |
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Preparation method |
Soleus and extensor digitorum longus muscles were excised from mice. The cells were suspended in incubation chambers containing 30℃ Krebs Ringer Henseleit (KRH) buffer supplemented with 8mM mannitol and 2mM pyruvate. The muscles were pre-incubated for 40min with 10μM SBI-0206965, and subsequently stimulated with or without 60nM Insulin for 20min. The total duration of the incubation experiments was 1h. |
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Reaction Conditions |
10μM ; 40min |
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Applications |
SBI-0206965 has a non-specific off-target inhibitory effect on muscle glucose transport. |
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Animal experiment[2]: |
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Animal models |
Male BALB/c nude mice |
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Preparation method |
A498 cells (5×106) suspended in 100μL PBS/Matrigel (1:1) were injected into the hind flank of the mice. After 14 days of implantation, the mice were randomly divided into two groups with 6 mice in each group. Mice were intraperitoneally injected SBI-0206965 in DMSO (50 mg/kg/d) every 3 day for a total of nine times over a 30 day period. |
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Dosage form |
50mg/kg ; intraperitoneally injected with SBI-0206965 ; 30 days |
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Applications |
SBI-0206965 blocks the kinase ULK1 activity with resulted in a level of anticancer effect in vivo. |
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References: [1] KNUDSEN J R, MADSEN A B, PERSSON K W, et al. The ULK1/2 and AMPK Inhibitor SBI-0206965 Blocks AICAR and Insulin-Stimulated Glucose Transport [J]. Int J Mol Sci, 2020, 21(7): [2] LU J, ZHU L, ZHENG L P, et al. Overexpression of ULK1 Represents a Potential Diagnostic Marker for Clear Cell Renal Carcinoma and the Antitumor Effects of SBI-0206965 [J]. EBioMedicine, 2018, 34(85-93. |
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| Cas No. | 1884220-36-3 | SDF | |
| 化学名 | (Z)-2-((5-bromo-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)oxy)-N-methylbenzimidic acid | ||
| Canonical SMILES | C/N=C(O)/C1=CC=CC=C1OC2=NC(NC3=CC(OC)=C(OC)C(OC)=C3)=NC=C2Br | ||
| 分子式 | C21H21BrN4O5 | 分子量 | 489.32 |
| 溶解度 | ≥ 24.5mg/mL in DMSO | 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 | 2.0437 mL | 10.2183 mL | 20.4365 mL |
| 5 mM | 0.4087 mL | 2.0437 mL | 4.0873 mL |
| 10 mM | 0.2044 mL | 1.0218 mL | 2.0437 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet