ICCB280
(Synonyms: (E)-2-(3,4-二羟基苯乙烯基)-3-(2-甲氧基苯基)喹唑啉-4(3H)-酮) 目录号 : GC61414
ICCB280是一种有效的C/EBPα诱导剂。ICCB280通过激活C/EBPα并影响其下游靶点(例如C/EBPε，G-CSFR和c-Myc)，具有抗白血病特性，包括终末分化，增殖停滞和凋亡。
Cas No.:2041072-41-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
ICCB280 is a potent inducer of C/EBPα. ICCB280 exhibits anti-leukemic properties including terminal differentiation, proliferation arrest, and apoptosis through activation of C/EBPα and affecting its downstream targets (such as C/EBPε, G-CSFR and c-Myc)[1][2].
ICCB280 (0.1-50 μM; 48 h) suppresses the HL-60 cell growth, with an IC50 of 8.6 μM[1].ICCB280 (10 μM; 2-8 d) increases the C/EBPα expression (mRNA and protein) and modulates its target genes in HL-60 cells[1].ICCB280 (10 μM; 7 d) induces granulocytic differentiation and subsequent apoptosis in HL-60 cells[1]. Cell Viability Assay[1] Cell Line: HL-60 cells
[1]. Radomska HS, et, al. A Cell-Based High-Throughput Screening for Inducers of Myeloid Differentiation. J Biomol Screen. 2015 Oct;20(9):1150-9. [2]. Sridhar R, et, al. Styryl Quinazolinones as Potential Inducers of Myeloid Differentiation via Upregulation of C/EBPα. Molecules. 2018 Aug 3;23(8):1938.
| Cas No. | 2041072-41-5 | SDF | |
| 别名 | (E)-2-(3,4-二羟基苯乙烯基)-3-(2-甲氧基苯基)喹唑啉-4(3H)-酮 | ||
| Canonical SMILES | O=C1N(C2=CC=CC=C2OC)C(/C=C/C3=CC=C(O)C(O)=C3)=NC4=C1C=CC=C4 | ||
| 分子式 | C23H18N2O4 | 分子量 | 386.4 |
| 溶解度 | DMSO: 83.33 mg/mL (215.66 mM) | 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 | 2.588 mL | 12.94 mL | 25.8799 mL |
| 5 mM | 0.5176 mL | 2.588 mL | 5.176 mL |
| 10 mM | 0.2588 mL | 1.294 mL | 2.588 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。
[Transcription factor-based therapies for acute myeloid leukemia]
Rinsho Ketsueki 2018;59(7):922-931.PMID:30078804DOI:10.11406/rinketsu.59.922.
Transcription factors are proteins that bind specific DNA-regulatory sequences and regulate gene transcription. In a hematopoietic system, transcription factors, such as C/EBPα, PU.1, and RUNX1, regulate the expression of essential genes to maintain the homeostasis in the bone marrow. The dysfunction of transcription factors mediated by gene mutations, chromosomal aberration, or aberrant expression can lead to cancer, including acute myeloid leukemia. Previously, transcription factors were not considered as therapeutic targets; however, a better understanding of cancer pathology and mechanisms underlying transcriptional regulation has enabled us to develop therapeutic agents that target transcription factors. C/EBPα is one of the essential transcription factors responsible for granulocytic differentiation and maturation. CEBPA mutation and/or low C/EBPα expression contribute to the pathogenesis of acute myeloid leukemia. Several therapeutic agents have been developed to increase C/EBPα activity, including ICCB280, which is a small molecule we identified by high-throughput screening. We believe that the novel therapeutic approach of targeting transcription factors will benefit patients with acute myeloid leukemia in the near future.
A Cell-Based High-Throughput Screening for Inducers of Myeloid Differentiation
J Biomol Screen 2015 Oct;20(9):1150-9.PMID:26109609DOI:10.1177/1087057115592220.
Recent progress of genetic studies has dramatically unveiled pathogenesis of acute myeloid leukemia (AML). However, overall survival of AML still remains unsatisfactory, and development of novel therapeutics is required. CCAAT/enhancer binding protein α (C/EBPα) is one of the crucial transcription factors that induce granulocytic differentiation, and its activity is perturbed in human myeloid leukemias. As its reexpression can induce differentiation and subsequent apoptosis of leukemic cells in vitro, we hypothesized that chemical compounds that restore C/EBPα expression and/or activity would lead to myeloid differentiation of leukemic cells. Using a cell-based high-throughput screening, we identified 2-[(E)-2-(3,4-dihydroxyphenyl)vinyl]-3-(2-methoxyphenyl)-4(3H)-quinazolinone as a potent inducer of C/EBPα and myeloid differentiation. Leukemia cell lines and primary blast cells isolated from human patients with AML treated with ICCB280 demonstrated evidence of morphological and functional differentiation, as well as massive apoptosis. We performed conformational analyses of the high-throughput screening hit compounds to postulate the spatial requirements for high potency. Our results warrant a development of novel differentiation therapies and significantly affect care of patients with AML with unfavorable prognosis in the near future.