UNC 0642
(Synonyms: 2-(4,4-二氟-1-哌啶基)-6-甲氧基-N-[1-异丙基-4-哌啶基]-7-[3-(1-吡咯烷基)丙氧基]-4-喹唑啉胺) 目录号 : GC14249
A G9a histone methyltransferase inhibitor
Cas No.:1481677-78-4
Sample solution is provided at 25 µL, 10mM.
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UNC0642 is a potent and selective G9a/GLP inhibitor, with an IC50 of less than 2.5 nM.
UNC0642 displays high in vitro and cellular potency, low cell toxicity, and excellent selectivity. UNC0642 is competitive with the peptide substrate and non-competitive with the cofactor SAM. The Ki of UNC0642 is determined to be 3.7±1 nM. UNC0642 displays high in vitro potency for GLP (IC50< 2.5 nM), similar to G9a. UNC0642 is more than 300-fold selective for G9a and GLP over a broad range of kinases, GPCRs, transporters, and ion channels. UNC0642 exhibits high potency at reducing the H3K9me2 mark, low cell toxicity, and good separation of functional potency and cell toxicity in a number of cell lines. It reduces clonogenicity in PANC-1 cells, a pancreatic carcinoma cell line[1].
A single intraperitoneal (IP) injection (5 mg/kg) of UNC0642results in a plasma Cmax (maximum concentration) of 947 ng/mL and an AUC (area under the curve) of 1265 hr*ng/mL[1].
References:
[1]. Liu F, et al. Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP. J Med Chem. 2013 Nov 14;56(21):8931-8942.
[2]. Wang L, et al. Targeting EHMT2 reverses EGFR-TKI resistance in NSCLC by epigenetically regulating the PTEN/AKT signaling pathway. Cell Death Dis. 2018 Jan 26;9(2):129
| Kinase experiment [1]: | |
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Kinase selectivity assays |
Selectivity of UNC 0642 against a panel of 50 kinases was conducted using a standard off-chip mobility shift assay technology. |
| Cell experiment [1]: | |
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Cell lines |
PANC-1 and MDA-MB-231 cells |
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Preparation method |
The solubility of this compound in DMSO is > 18.5 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0, 0.5 or 1 μM; 2 weeks |
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Applications |
UNC 0642 concentration-dependently reduced clonogenicity in PANC-1 cells but it showed no effect on clonogenicity in MDA-MB-231 cells. Besides, UNC 0642 potently reduced cellular levels of H3K9me2 with low cell toxicity, which resulted in a good separation of functional potency and cell toxicity with a tox/function ratio of 88 in PANC-1 cells. |
| Animal experiment [1]: | |
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Animal models |
Male Swiss Albino mice |
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Dosage form |
5 mg/kg; i.p. |
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Applications |
A single intraperitoneal injection of 5 mg/kg UNC 0642 resulted in a plasma Cmax of 947 ng/mL and an AUC of 1265 h·ng/mL. However, UNC 0642 only displayed modest brain penetration, with a brain/plasma ratio of 0.33, which suggested that UNC 0642 might not be suitable for exploration of the role of G9a/GLP in the CNS. |
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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]. Liu F, Barsyte-Lovejoy D, Li F, Xiong Y, Korboukh V, Huang XP, Allali-Hassani A, Janzen WP, Roth BL, Frye SV, Arrowsmith CH, Brown PJ, Vedadi M, Jin J. Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP. J Med Chem. 2013 Nov 14;56(21):8931-42. | |
| Cas No. | 1481677-78-4 | SDF | |
| 别名 | 2-(4,4-二氟-1-哌啶基)-6-甲氧基-N-[1-异丙基-4-哌啶基]-7-[3-(1-吡咯烷基)丙氧基]-4-喹唑啉胺 | ||
| 化学名 | 2-(4,4-difluoropiperidin-1-yl)-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazolin-4-amine | ||
| Canonical SMILES | CC(C)N1CCC(NC2=NC(N3CCC(F)(F)CC3)=NC4=C2C=C(OC)C(OCCCN5CCCC5)=C4)CC1 | ||
| 分子式 | C29H44F2N6O2 | 分子量 | 546.7 |
| 溶解度 | ≥ 18.5mg/mL in DMSO | 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 | 1.8292 mL | 9.1458 mL | 18.2916 mL |
| 5 mM | 0.3658 mL | 1.8292 mL | 3.6583 mL |
| 10 mM | 0.1829 mL | 0.9146 mL | 1.8292 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet