Sulanemadlin
(Synonyms: ALRN-6924; MP-4897) 目录号 : GC69968Sulanemadlin是一种基于p53靶点的膜渗透性强效大环拟肽化合物，是一种稳定的α-螺旋肽。
Cas No.:1451199-98-6
Sample solution is provided at 25 µL, 10mM.
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Sulanemadlin is a membrane-permeable, potent macrocyclic peptidomimetic compound based on the p53 target, and is a stable α-helical peptide[1]. The mechanism of action of Sulanemadlin is to selectively antagonize the protein-protein interaction between mouse double minute 4 homolog (MDMX) or mouse double minute 2 homolog (MDM2) and p53, thereby relieving the inhibitory state of p53 in tumor cells[2]. Sulanemadlin can be used to study hematological malignancies[3].
In vitro, Sulanemadlin (10μM) treatment of MCF-7 and ZR-75-1 cells for 24h increased p53 levels, reduced the S phase cell population, and induced cell apoptosis[4].
In vivo, Sulanemadlin (8, 12, 20mg/kg) was intravenously injected into acute myeloid leukemia (AML) cell xenograft mice, significantly improving the survival rate of mice, and the animals in the treatment group appeared healthy throughout the treatment process without signs of thrombocytopenia[5]. Sulanemadlin (2.4mg/kg) was administered intravenously to irradiated mice, inducing cell cycle arrest in the mouse bone marrow and providing significant protection against radiation-induced weight loss[6].
References:
[1] Guerlavais V, Sawyer T K, Carvajal L, et al. Discovery of Sulanemadlin (ALRN-6924), the first cell-permeating, stabilized α-helical peptide in clinical development[J]. Journal of Medicinal Chemistry, 2023, 66(14): 9401-9417.
[2] Casciano F, Zauli E, Busin M, et al. State of the art of pharmacological activators of p53 in ocular malignancies[J]. Cancers, 2023, 15(14): 3593.
[3] Carvajal L A, Ben-Neriah D, Senecal A, et al. Dual inhibition of Mdmx and Mdm2 using an alpha-helical P53 stapled peptide (ALRN-6924) as a novel therapeutic strategy in acute myeloid leukemia[J]. Blood, 2017, 130: 795.
[4] Pairawan S, Zhao M, Yuca E, et al. First in class dual MDM2/MDMX inhibitor ALRN-6924 enhances antitumor efficacy of chemotherapy in TP53 wild-type hormone receptor-positive breast cancer models[J]. Breast Cancer Research, 2021, 23: 1-15.
[5] Carvajal L A, Neriah D B, Senecal A, et al. Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia[J]. Science translational medicine, 2018, 10(436): eaao3003.
[6] Annis A, Sutton D, Aivado M, et al. Alrn-6924, a Dual Inhibitor of MDMX and MDM2, Transiently Induces Cell Cycle Arrest in Bone Marrow and Prevents Toxicity in Mouse Models of Acute Radiation Injury[J]. Blood, 2021, 138(Supplement 1): 2947-2947.
Sulanemadlin是一种基于p53靶点的膜渗透性强效大环拟肽化合物，是一种稳定的α-螺旋肽[1]。Sulanemadlin的作用机制是通过选择性拮抗小鼠双微体4同源物（MDMX）或小鼠双微体2同源物（MDM2）与p53的蛋白-蛋白相互作用，解除肿瘤细胞中p53的抑制状态[2]。Sulanemadlin能够用于血液系统恶性肿瘤的研究[3]。
在体外，Sulanemadlin（10μM）处理MCF-7、ZR-75-1细胞24h，增加了p53水平，减少了S期细胞群，诱导了细胞凋亡[4]。
在体内，Sulanemadlin（8, 12, 20mg/kg）通过静脉注射治疗急性髓细胞白血病 （AML）细胞异种移植小鼠，显著提高了小鼠存活率，且治疗组动物在整个治疗过程中都表现得很健康，没有出现血小板减少的迹象[5]。Sulanemadlin（2.4mg/kg）通过静脉注射治疗辐射损伤小鼠，诱导了小鼠骨髓中的细胞周期停滞，对辐射诱导的体重损失产生了显著保护[6]。
| Cell experiment [1]: | |
Cell lines | MCF-7、ZR-75-1 cells |
Preparation Method | Cells were plated and treated the following day in duplicates for 24h with either vehicle, Sulanemadlin 10μM, paclitaxel 1μM, or combination of both. Samples were collected, fixed, stained with PI, and analyzed by flow cytometry in the MDACC Flow Cytometry and Cellular Imaging Core Facility. |
Reaction Conditions | 10μM; 24h |
Applications | The cell population in S phase was decreased in both the combination and single agent Sulanemadlin treatment groups. |
| Animal experiment [2]: | |
Animal models | C57/BL6 mice |
Preparation Method | Animals were transplanted via tail vein injections of 2.0×105 cells, using either MOLM13 or ML2 human AML cells and randomly assigned to experimental groups. All groups were dosed with vehicle (phosphate-buffered saline), Sulanemadlin (8mg/kg), Sulanemadlin (12mg/kg), or Sulanemadlin (20mg/kg) at a frequency of twice per week for 10 weeks or three times per week for 5 weeks. The end point of these in vivo experiments was overall survival. All animals were sacrificed upon visual signs of dis ease progression. Exclusion criteria included unspecified death and body weight loss of more than 20%. |
Dosage form | 8, 12, 20mg/kg; twice per week for 10 weeks or three times per week for 5 weeks; i.v. |
Applications | Sulanemadlin markedly improves survival in AML xenograft models. |
References: | |
| Cas No. | 1451199-98-6 | SDF | Download SDF |
| 别名 | ALRN-6924; MP-4897 | ||
| 分子式 | C95H140N20O23 | 分子量 | 1930.25 |
| 溶解度 | DMSO : ≥ 100 mg/mL (51.81 mM) | 储存条件 | Store at -20°C,Sealed storage, away from moisture and light, under nitrogen |
| 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 | 0.5181 mL | 2.5903 mL | 5.1807 mL |
| 5 mM | 0.1036 mL | 0.5181 mL | 1.0361 mL |
| 10 mM | 0.0518 mL | 0.259 mL | 0.5181 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: >96.50%
- COA (Certificate Of Analysis)
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