CCT020312
目录号 : GC33006
CCT020312是一种选择性蛋白激酶R样内质网激酶（PERK）通路激动剂。
Cas No.:324759-76-4
Sample solution is provided at 25 µL, 10mM.
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CCT020312 is a selective protein kinase R-like endoplasmic reticulum kinase (PERK) pathway agonist [1]. CCT020312 activates the endoplasmic reticulum stress (ER stress)-related unfolded protein response (UPR) pathway by promoting eIF2α phosphorylation and upregulating ATF4 expression, thereby inducing cell cycle arrest and autophagy [2-3]. CCT020312 is often used to study diseases such as tumors and neurodegenerative diseases [4].
In MDA-MB-453 and CAL-148 cells, CCT020312 (2-12μM; 24h, 48h) significantly inhibited cell viability in a dose-dependent manner [5]. In HT29 cells, CCT020312 (1-9μM; 24h) treatment effectively inhibited cell proliferation [6]. In HCT116 and SW480 cells, CCT020312 (0.625-50μM; 12h, 24h, 48h) exposure reduced the cell viability of cell in a time- and dose-dependent manner [7].
In nflammation-mediated osteoporosis (IMO) rat model, CCT020312 (1mg/kg, 2mg/kg; ip; 20d) significantly alleviated the osteoporosis symptoms of IMO rats by improving bone remodeling indicators, increasing bone density, promoting osteogenesis, and inhibiting bone resorption and inflammation [8]. In aged mice, activation of PERK with CCT020312 (2mg/kg; ip; single injection) increases the amount of GluN2A and GluN2B in synaptosomal preparations [9].
References:
[1]. Bruch J, Xu H, Rösler TW, et al. PERK activation mitigates tau pathology in vitro and in vivo. EMBO molecular medicine. 2017 Mar; 9(3): 371-384.
[2]. Stockwell SR, Platt G, Barrie SE, et al. Mechanism-based screen for G1/S checkpoint activators identifies a selective activator of EIF2AK3/PERK signalling. PloS one. 2012 Jan 12; 7(1): e28568.
[3]. Zhou D, Yin M, Kang B, et al. CCT020312 exerts anti-prostate cancer effect by inducing G1 cell cycle arrest, apoptosis and autophagy through activation of PERK/eIF2α/ATF4/CHOP signaling. Biochemical pharmacology. 2024 Mar 1; 221: 116038.
[4]. Talukdar G, Orr HT, Lei Z. The PERK pathway: beneficial or detrimental for neurodegenerative diseases and tumor growth and cancer. Human molecular genetics. 2023 Aug 15; 32(16): 2545-2557.
[5]. Li X, Yu X, Zhou D, et al. CCT020312 inhibits triple-negative breast cancer through PERK pathway-mediated G1 phase cell cycle arrest and apoptosis. Frontiers in Pharmacology. 2020 May 19; 11: 737.
[6]. Stockwell SR, Platt G, Barrie SE, et al. Mechanism-based screen for G1/S checkpoint activators identifies a selective activator of EIF2AK3/PERK signalling. PloS one. 2012 Jan 12; 7(1): e28568.
[7]. Lei Y, He L, Yan C, et al. PERK activation by CCT020312 chemosensitizes colorectal cancer through inducing apoptosis regulated by ER stress. Biochemical and biophysical research communications. 2021 Jun 11; 557: 316-322.
[8]. Tang BM, Li ZW, Wang ZY. PERK activator CCT020312 prevents inflammation-mediated osteoporosis in the ovariectomized rats. Gynecological Endocrinology. 2021 Apr 3; 37(4): 342-348.
[9]. Chen K, Hu Q, Gupta R, et al. Inhibition of unfolded protein response prevents post‐anesthesia neuronal hyperactivity and synapse loss in aged mice. Aging Cell. 2022 Apr; 21(4): e13592.
CCT020312是一种选择性蛋白激酶R样内质网激酶（PERK）通路激动剂 [1]。CCT020312通过促进eIF2α磷酸化和上调ATF4表达来激活内质网应激（ER stress）相关的未折叠蛋白反应（UPR）通路，从而诱导细胞周期停滞和自噬 [2-3]。CCT020312常用于研究肿瘤和神经退行性疾病等疾病 [4]。
在MDA-MB-453和CAL-148细胞中，CCT020312（2-12μM；24h，48h）以剂量依赖性方式显著抑制细胞活力 [5]。在HT29细胞中，CCT020312（1-9μM；24h）处理可有效抑制细胞增殖 [6]。在HCT116和SW480细胞中，CCT020312（0.625-50μM；12h，24h，48h）暴露以时间和剂量依赖性方式降低细胞活力 [7]。
在炎症介导的骨质疏松症（IMO）大鼠模型中，CCT020312（1mg/kg，2mg/kg；ip；20d）通过改善骨重建指标、增加骨密度、促进成骨、抑制骨吸收和炎症，显著缓解IMO大鼠的骨质疏松症状 [8]。在老年小鼠中，用CCT020312（2mg/kg；ip；单次注射）激活PERK可增加突触体制剂中GluN2A和GluN2B的含量 [9]。
| Cell experiment [1]: | |
Cell lines | MDA-MB-453 and CAL-148 cells |
Preparation Method | MDA-MB-453 (8 × 103 cells/well) and CAL-148 cells (4 × 103 cells/well) were seeded in 96-well plates and treated with CCT020312 at different doses for 24 or 48h. Then, 10µl of CCK-8 solution was added to each well and incubated for 1 or 2h at 37℃. |
Reaction Conditions | 2-12μM; 24h, 48h |
Applications | CCT020312 significantly inhibited cell viability in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Inflammation-mediated osteoporosis (IMO) rat model |
Preparation Method | CCT020312 (CCT) was dissolved in 100μL sterile dimethyl sulfoxide (DMSO) and diluted by sterile normal saline to the density of 0.5mg/mL. Rats (n = 24) were randomly divided into four groups: Sham group, IMO group, IMO + 1mg/kg CCT group and IMO + 2mg/kg CCT group, with 6 rats in each group. All rats except for those in the Sham group were made into IMO models by bilateral ovariectomy (OVX) and magnesium silicate (Talc) injection. In brief, rats were anesthetized with an intraperitoneal injection of pentobarbital sodium (20mg/kg), OVX operation was performed (1st day), and metamizole sodium (25mg/kg) was administered to rats for two consecutive days. Sham rats did not receive OVX operation and only a little fatty tissue around the ovary was resected. On the 59th day after OVX operation, which allowed for osteoporosis to develop in the OVX rats, inflammation was induced by subcutaneously injected with Talc (magnesium silicate: 3.2 g in total per animal) in sterile saline in the back of the rats. Meanwhile, only the rats in the Sham group were subcutaneously injected with saline. From the 60th day on, rats were given with intraperitoneal injection (i.p.) of DMSO (vehicle control) or CCT (1mg/kg/day and 2mg/kg/day). Then, the rats were sacrificed through an overdose of thiopental sodium (50mg/kg) on the 80th day. |
Dosage form | 1mg/kg, 2mg/kg; ip; 20d |
Applications | CCT020312 significantly alleviated the osteoporosis symptoms of IMO rats by improving bone remodeling indicators, increasing bone density, promoting osteogenesis, and inhibiting bone resorption and inflammation. |
References: | |
| Cas No. | 324759-76-4 | SDF | |
| Canonical SMILES | O=C1NC2=C(C(C3=CC=CC=C3)=C1C4=NN(C(C4)C5=CC=C(C=C5)Br)C(CCN(CC)CC)=O)C=C(C=C2)Br | ||
| 分子式 | C31H30Br2N4O2 | 分子量 | 650.4 |
| 溶解度 | DMSO : 125 mg/mL (192.19 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 | 1.5375 mL | 7.6876 mL | 15.3752 mL |
| 5 mM | 0.3075 mL | 1.5375 mL | 3.075 mL |
| 10 mM | 0.1538 mL | 0.7688 mL | 1.5375 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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Quality Control & SDS
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- Purity: >98.00%
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