I-CBP 112
目录号 : GC17944
A p300 and CBP inhibitor
Cas No.:1640282-31-0
Sample solution is provided at 25 µL, 10mM.
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Description:IC50: 170 nm (CREBBP/EP300)
A bromodomain is an approximately 110 amino acid protein domain that recognizes monoacetylated lysine residues such as those on the N-terminal tails of histones. Members of the BET family (Bromodomain and extraterminal domain family) have been implicated as targets in human cancer. Inhibitors of BET have shown therapeutic effects in multiple models of hematological malignancies as well as solid tumors. SGC have developed an inhibitor, I-CBP112, against the CREBBP and EP300 Bromodomains.
In vitro: A CREBBP/EP300-selective chemical probe from a completely different structural class which was also developed by the SGC is I-CBP112. I-CBP112 has an IC50 value of 170 nm in the CREBBP AlphaScreen assay, and is selective against the bromodomain proteins ATAD2, BAZ2B, BRD2(BD2), BRD4 (BD1), PB1(BD5), PCAF, PHIP(BD2), TRIM24/TIF-1a. In U2OS cells no significant cytotoxicity up to 50 mm was found. Similar to bromosporine 129, data related to SGCCBP30 and I-CBP112 are reported on the SGC homepage exclusively [1].
In vivo: Currently, I-CBP112 is still in the in-vitro investigation, and no animal in-vivo study is on-going.
Clinical trial: I-CBP112 is currently in the preclinical development and no clinical trial is ongoing.
References:
[1] Gallenkamp D, Gelato KA, Haendler B, Weinmann H. Bromodomains and their pharmacological inhibitors. ChemMedChem. 2014;9(3):438-64.
| Cell experiment [1]: | |
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Cell lines |
Immortalized murine bone marrow cells, human leukemic cells |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.1-10 μM, 48 h or 72 h |
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Applications |
In immortalized murine bone marrow cells, I-CBP112 (0.1-10 μM, 48 h or 72 h) impaired clonogenic growth of immortalized murine bone marrow cells. In immortalized murine bone marrow cells, I-CBP112 (10 μM, 72 h) showed significant cytotoxicity. I-CBP112 significantly reduced clonogenic growth of MLL-CBP immortalized cells in MC cells. I-CBP112 (3 μM, 3 days) impaired the clonogenic growth of human leukemic cells and sensitized them to BET inhibition and doxorubicin. |
| Animal experiment [1]: | |
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Animal models |
Mice transplanted with bone marrow retrovirally expressing fusion oncogenes |
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Dosage form |
5 μM, 3 days |
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Application |
I-CBP112 pre-treatment of MLL-AF9+ murine AML blasts reduced the number of LICs and delayed induction of the disease upon transplantation into irradiated recipients. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Picaud S, Fedorov O, Thanasopoulou A, et al. Generation of a selective small molecule inhibitor of the CBP/p300 bromodomain for leukemia therapy[J]. Cancer research, 2015, 75(23): 5106-5119. | |
| Cas No. | 1640282-31-0 | SDF | |
| 化学名 | (S)-1-(7-(3,4-dimethoxyphenyl)-9-((1-methylpiperidin-3-yl)methoxy)-2,3-dihydrobenzo[f][1,4]oxazepin-4(5H)-yl)propan-1-one | ||
| Canonical SMILES | COC1=C(OC)C=C(C2=CC(OC[C@H]3CCCN(C)C3)=C(OCCN4C(CC)=O)C(C4)=C2)C=C1 | ||
| 分子式 | C27H36N2O5 | 分子量 | 468.59 |
| 溶解度 | Soluble to 100 mM in DMSO and to 100 mM in 1eq. HCl | 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。 |
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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 | 2.1341 mL | 10.6703 mL | 21.3406 mL |
| 5 mM | 0.4268 mL | 2.1341 mL | 4.2681 mL |
| 10 mM | 0.2134 mL | 1.067 mL | 2.1341 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