PROTAC-O4I2
目录号 : GC63916
PROTAC-O4I2是一种2-氨基噻唑衍生物，能够选择性降解SF3B1并以CRBN依赖的方式诱导细胞凋亡（IC50 = 0.244μM）。
Sample solution is provided at 25 µL, 10mM.
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PROTAC-O4I2 is a 2-aminothiazole derivative that selectively degrades SF3B1 and induces apoptosis in a CRBN-dependent manner (IC50 = 0.244μM) [1]. PROTAC-O4I2 is commonly used to treat cancer [2].
In K562 cells, PROTAC-O4I2 (1µM; 48h) induces apoptosis in K562 WT cells [1]. In K562 overexpressing SF3B1WT, there is an inversion of the cytotoxicity profiles, making PROTAC-O4I2 (1µM; 72h) twice as effective as Pladienolide B against cell viability [3].
In tumor bearing flies models, administration of PROTAC-O4I2 (10μM; po; 30d) significantly reduced stem cell activity and tumor growth in the intestine of CRISPR/Cas9-mediated Notch knockout (Notch-gRNA2x) animals [1].
References:
[1]. Gama-Brambila RA, Chen J, Zhou J, et al. A PROTAC targets splicing factor 3B1. Cell chemical biology. 2021 Nov 18; 28(11): 1616-1627.
[2]. Chen Y, Yang Q, Xu J, et al. PROTACs in gastrointestinal cancers. Molecular Therapy-Oncolytics. 2022 Dec 15; 27: 204-223.
[3]. Gama Brambila RA. Biological Assessment and Tests of Activity of Two Novel Proteolysis Targeting Chimeras (PROTACs) (Doctoral dissertation).
PROTAC-O4I2是一种2-氨基噻唑衍生物，能够选择性降解SF3B1并以CRBN依赖的方式诱导细胞凋亡（IC50 = 0.244μM） [1]。PROTAC-O4I2常用于治疗癌症 [2]。
在K562细胞中，PROTAC-O4I2（1µM；48h）诱导K562野生型细胞凋亡 [1]。在过表达SF3B1WT的K562细胞中，细胞毒性谱发生了逆转，使得 PROTAC-O4I2（1µM；72h）对细胞活力的抑制作用是Pladienolide B的两倍 [3]。
在患有肿瘤的果蝇模型中，施用PROTAC-O4I2（10μM；po；30d）显著降低了CRISPR/Cas9介导的Notch敲除（Notch-gRNA2x）动物肠道中的干细胞活性和肿瘤生长 [1]。
| Cell experiment [1]: | |
Cell lines | K562 cells |
Preparation Method | Annexin v and propidium iodide staining assay was used to detect the apoptotic cells in K562 cell treated with compounds as previously reported. Briefly, K562 cells were seeded at a density of 200 000 cells/well in a 12-well plate. Pladienolide (1μM), PROTAC-O4I2 (1μM) or DMSO (mock) was added as designed and incubated for 48h. |
Reaction Conditions | 1µM; 48h |
Applications | PROTAC-O4I2 induces apoptosis in K562 WT cells. |
| Animal experiment [1]: | |
Animal models | Tumor bearing flies models |
Preparation Method | To evaluate the anti-tumor effect of PROTAC-O4I2, control (esgts, UAS-Cas9P2>sepia-gRNA2X) and tumor bearing flies (esgts, UAS-Cas9P2>Notch-gRNA2X) were kept in a cage and fed on a round filter paper loaded with 10μM PROTAC-O4I2 in a 5% sucrose solution. |
Dosage form | 10μM; po; 30d |
Applications | In isoflurane anesthetized mice, metoprolol caused a reduction in HR, SV, and CO, while SVR increased. |
References: | |
| Cas No. | SDF | Download SDF | |
| 分子式 | C29H29ClN6O5S | 分子量 | 609.1 |
| 溶解度 | DMSO : 250 mg/mL (410.44 mM; Need ultrasonic) | 储存条件 | Store at -20°C,protect from light |
| 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 | 1.6418 mL | 8.2088 mL | 16.4177 mL |
| 5 mM | 0.3284 mL | 1.6418 mL | 3.2835 mL |
| 10 mM | 0.1642 mL | 0.8209 mL | 1.6418 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet