PRIMA-1MET
(Synonyms: APR-246) 目录号 : GC11247
PRIMA-1MET是一种能够恢复肿瘤抑制功能的小分子有机化合物，主要靶向突变型p53，诱导多种癌细胞死亡。
Cas No.:5291-32-7
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
PRIMA-1MET is a small molecule organic compound that can restore tumor suppression function, mainly targeting mutant p53 and inducing cell death in various types of cancer cells[1]. PRIMA-1MET is hydrolyzed into the active form of methylquinine cycloketone within cells and covalently binds to the thiol group of the core domain of the mutant p53 protein, thereby causing structural changes and restoring the active conformation of p53 protein [2]. PRIMA-1MET has been widely used in anti-cancer research[3].
In vitro, PRIMA-1MET inhibits the cell viability of BWM-1 cells (IC50 value=30μM) and MWCL-1 cells (IC50 value= 28μM) after treatment of 48 hours[4]. PRIMA-1MET treatment (60µM) for 24 hours significant induced autophagy and enhanced the mTOR/AMPK-ULK1-Vps34 autophagic signaling cascade in colorectal cancer (CRC) cells[5]. PRIMA-1 MET (100μM; 72H) effectively inhibited the growth of small cell lung cancer (SCLC) cell lines expressing mutant p53 induced apoptosis, accompanied by an increase in the proportion of DNA fragmented cells, caspase-3 activation, and downregulation of Bcl-2 expression[6].
In vivo, PRIMA-1MET treatment (100mg/kg/day; i.p.) for 15 consecutive days can inhibit the growth of multiple myeloma tumors containing mutant p53 in multiple myeloma xenograft SCID mouse models[7]. Intraperitoneal injection of PRIMA-1MET at the dosage of 100mg/kg/day for 5 consecutive days significantly reduced the tumor size and tumor volume in the mouse model of rectal cancer xenograft tumors, decreased ERK1/2 phosphorylation, and inhibited MEK activity[8].
References:
[1] Perdrix, A.; Najem, A.; Saussez, S.; Awada, A.; Journe, F.; Ghanem, G.; Krayem, M. PRIMA-1 and PRIMA-1Met (APR-246): From Mutant/Wild Type p53 Reactivation to Unexpected Mechanisms Underlying Their Potent Anti-Tumor Effect in Combinatorial Therapies. Cancers 2017, 9, 172.
[2] Xie X, Fan C, Luo B, et al. APR-246 enhances colorectal cancer sensitivity to radiotherapy[J]. Molecular cancer therapeutics, 2023, 22(8): 947-961.
[3] Menichini P, Monti P, Speciale A, et al. Antitumor effects of PRIMA-1 and PRIMA-1Met (APR246) in hematological malignancies: still a mutant p53-dependent affair?[J]. Cells, 2021, 10(1): 98.
[4] Sobhani M, Kwan K, Saha M N, et al. Small molecule PRIMA-1 met sensitizes Waldenstrom macroglobulinemia cells to apoptosis and displays synergistic cytotoxicity with bortezomib[J]. Blood, 2013, 122(21): 5143.
[5] Li X L, Zhou J, Xia C J, et al. PRIMA-1met induces autophagy in colorectal cancer cells through upregulation of the mTOR/AMPK-ULK1-Vps34 signaling cascade[J]. Oncology Reports, 2021, 45(5): 86.
[6] Zandi R, Selivanova G, Christensen C L, et al. PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53[J]. Clinical Cancer Research, 2011, 17(9): 2830-2841.
[7] Saha M N, Jiang H, Yang Y, et al. PRIMA-1Met/APR-246 displays high antitumor activity in multiple myeloma by induction of p73 and Noxa[J]. Molecular cancer therapeutics, 2013, 12(11): 2331-2341.
[8] Lu T, Zou Y, Xu G, et al. PRIMA-1Met suppresses colorectal cancer independent of p53 by targeting MEK[J]. Oncotarget, 2016, 7(50): 83017.
PRIMA-1MET是一种能够恢复肿瘤抑制功能的小分子有机化合物，主要靶向突变型p53，诱导多种癌细胞死亡[1]。PRIMA-1MET在细胞内水解为活性形式的甲基喹啉环酮，并通过共价结合突变p53蛋白核心结构域的巯基，引发构象改变并恢复p53蛋白活性[2]。PRIMA-1MET已被广泛应用于抗癌研究领域[3]。
在体外，处理48小时后，PRIMA-1MET可抑制BWM-1细胞（IC50=30μM）和MWCL-1细胞（IC50=28μM）的活性[4]。在结直肠癌细胞中，60µM浓度的PRIMA-1MET处理24小时显著诱导自噬，并增强mTOR/AMPK-ULK1-Vps34自噬信号通路[5]。100μM 浓度的PRIMA-1MET处理72小时能有效抑制表达突变p53的小细胞肺癌（SCLC）细胞系生长，诱导细胞凋亡，伴随着DNA片段化细胞比例增加，caspase-3激活及Bcl-2表达下调[6]。
在体内，连续15天的PRIMA-1MET（100mg/kg/day；i.p）处理可抑制多发性骨髓瘤SCID小鼠移植瘤模型中含突变p53的肿瘤生长[7]。在直肠癌移植瘤小鼠模型中，连续5天腹腔注射PRIMA-1MET（100mg/kg/day）显著减小肿瘤体积，降低ERK1/2磷酸化水平并抑制MEK活性[8]。
| Cell experiment [1]: | |
Cell lines | KKU-100 cell |
Preparation Method | KKU-100 cells were cultured in the modified Eagle medium (DMEM) supplemented with 10% heat-inactivated fetal bovine serum (FBS), 2mg/ml sodium bicarbonate and 1% antibiotic solution. All cells were cultured in a humidified incubator at 37℃ with a concentration of 5% CO2. KKU-100 cells (2×103) suspended in 100μl of medium were inoculated into 96-well plates in triplicate. Cells were treated with PRIMA-1MET at different concentrations (0, 20, 40, 60, 80, and 100μM) for 48 hours. Cell viability was determined using sulfonylrhodamine B (SRB). The absorbance was measured at 540nm using a microplate reader. |
Reaction Conditions | 0, 20, 40, 60, 80, and 100μM; 48h |
Applications | PRIMA-1MET significantly inhibited the viability of KKU-100 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Balb/c mice |
Preparation Method | Five Balb/ c mice in three groups were subcutaneously inoculated with 5×105MCO4 cells. On the 7th day after inoculation, PBS or PRIMA-1MET at a dose of 100mg/kg was intravenously injected into the tail vein of mice once a day for 10 consecutive days. During the observation period, body weight and tumor size were monitored starting from vaccination. The tumor was immediately fixed in 4% formaldehyde for 12 hours after resection, stored in 70% ethanol at 4℃, and then embedded in paraffin. Hematoxylin and eosin staining were carried out according to the standard protocol. According to the manufacturer's instructions, apoptotic cells were detected in situ using TUNEL. |
Dosage form | 100mg/kg for 10 days; i.v. |
Applications | PRIMA-1MET treatment significantly suppressed tumor growth, and increased the survival rate of mice without obvious toxicity. |
References: | |
| Cas No. | 5291-32-7 | SDF | |
| 别名 | APR-246 | ||
| 化学名 | 2-(hydroxymethyl)-2-(methoxymethyl)-1-azabicyclo[2.2.2]octan-3-one | ||
| Canonical SMILES | COCC1(C(=O)C2CCN1CC2)CO | ||
| 分子式 | C10H17NO3 | 分子量 | 199.25 |
| 溶解度 | ≥ 19.9mg/mL in DMSO, ≥ 102 mg/mL in EtOH with ultrasonic, ≥ 104.2 mg/mL in Water | 储存条件 | Store at 4°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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 5.0188 mL | 25.0941 mL | 50.1882 mL |
| 5 mM | 1.0038 mL | 5.0188 mL | 10.0376 mL |
| 10 mM | 0.5019 mL | 2.5094 mL | 5.0188 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
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet