CC-92480（Mezigdomide）是一种新型的Cereblon（CRBN）E3连接酶调节剂（CELMoD），常以分子胶的方式发挥作用，具有增强的肿瘤和免疫调节活性。
Cas No.:2259648-80-9
Sample solution is provided at 25 µL, 10mM.
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CC-92480 (Mezigdomide) is a novel Cereblon (CRBN) E3 ligase modulator (CELMoD) that typically functions as a molecular glue, exhibiting enhanced anti-tumor and immunomodulatory activities[1, 2]. CC-92480 is orally bioavailable and is indicated for the treatment of relapsed and refractory multiple myeloma[3]. Compared to conventional immunomodulatory drugs (IMiDs, such as lenalidomide and pomalidomide), CC-92480 demonstrates a stronger binding affinity for CRBN[4].
In vitro, treatment of lenalidomide-resistant H929 R10-1 cells with CC-92480 (1-100nM) for 4h induced the complete degradation of Ikaros and Aiolos proteins[3].
In vivo, treatment with CC-92480 (10mg/kg) for 28 to 55 days significantly improved the median survival of mice across four distinct patient-derived xenograft (PDX) models of acute myeloid leukemia (AML)[5].
References:
[1] Fernandez Forner D F, Fernandez-Llamazares A I. American Chemical Society-258th National Meeting and Exposition. San Diego, California, USA-August 25-29, 2019[J]. Drugs of the Future, 2019, 44(9).
[2] Lopez-Girona A, Havens C G, Lu G, et al. CC-92480 is a novel cereblon E3 ligase modulator with enhanced tumoricidal and immunomodulatory activity against sensitive and resistant multiple myeloma cells[J]. Blood, 2019, 134: 1812.
[3] Hansen J D, Correa M, Nagy M A, et al. Discovery of CRBN E3 ligase modulator CC-92480 for the treatment of relapsed and refractory multiple myeloma[J]. Journal of medicinal chemistry, 2020, 63(13): 6648-6676.
[4] Rajendran G. Investigation of the anticancer activity and mechanisms of zinc diethyldithiocarbamate in multiple myeloma[J]. 2023.
[5] Bourgeois W, Aubrey B J, Cutler J A, et al. Potent Ikaros degradation by the cereblon E3 ligase modulator CC-92480 is effective in combination with Menin-MLL1 inhibition in MLL1-rearranged and NPM1-mutant AML[J]. Blood, 2021, 138: 208.
CC-92480（Mezigdomide）是一种新型的Cereblon（CRBN）E3连接酶调节剂（CELMoD），常以分子胶的方式发挥作用，具有增强的肿瘤和免疫调节活性[1, 2]。CC-92480具有口服活性，能够用于治疗复发和难治性多发性骨髓瘤[3]。CC-92480与传统的免疫调节剂（IMiDs，如lenalidomide、pomalidomide）相比具有更强的CRBN结合亲和力[4]。
在体外，CC-92480（1-100nM）处理lenalidomide耐药细胞H929 R10-1细胞4h，诱导了Ikaros和Aiolos蛋白完全降解[3]。
在体内，CC-92480（10mg/kg）治疗四种急性骨髓性白血病（AML）患者来源异种移植（PDX）模型小鼠28-55天，在四种PDX模型中均显著提高了小鼠的中位生存率[5]。
| Animal experiment [1]: | |
Animal models | NSG-S mice |
Preparation Method | NSG-S mice were engrafted with PDX samples (>7 mice per treatment cohort). Following detection of leukemia in peripheral blood, mice were randomized to receive vehicle control, lenalidomide 50mg/kg (in two of the four PDXs), or CC-92480 10mg/kg for 28-55 days and survival benet was assessed. |
Dosage form | 10mg/kg; 28-55 days |
Applications | In these models, CC-92480 increased median survival compared to DMSO by 28.3% (p<0.05), 66% (p<0.0005), 128% (p<0.0005), and 133% (p<0.0001). In two of these experiments CC-92480 was also compared to lenalidomide and increased survival by 23.4% (p<0.0005) and 28.1% (p<0.05). |
References: | |
| Cas No. | 2259648-80-9 | SDF | |
| 别名 | CC-92480 | ||
| Canonical SMILES | N#CC1=CC=C(N2CCN(CC3=CC=C(COC4=CC=CC5=C4CN([C@@H](CC6)C(NC6=O)=O)C5=O)C=C3)CC2)C(F)=C1 | ||
| 分子式 | C32H30FN5O4 | 分子量 | 567.61 |
| 溶解度 | DMSO: 5 mg/mL (8.81 mM; ultrasonic and warming and heat to 60°C) | 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 | 1.7618 mL | 8.8089 mL | 17.6177 mL |
| 5 mM | 352.4 μL | 1.7618 mL | 3.5235 mL |
| 10 mM | 176.2 μL | 880.9 μL | 1.7618 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% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet