GSK2879552
目录号 : GC11578
An LSD1 inhibitor
Cas No.:1401966-69-5
Sample solution is provided at 25 µL, 10mM.
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Description:
EC50: 38 nM for anti-proliferative growth effect in 19 of 25 AML cell lines
Lysine specific demethylase 1 (LSD1) is a histone H3K4me1/2 demethylase found in various transcriptional co-repressor complexes. LSD1 can interact with pluripotency factors in human embryonic stem cells and is important for decommissioning enhancers in stem cell differentiation. LSD1 is overexpressed in multiple cancer types and recent studies suggest inhibition of LSD1 reactivates the all-trans retinoic acid receptor pathway in acute myeloid leukemia (AML). GSK2879552 is a novel and irreversible LSD1 inhibitor.
In vitro: Six days of GSK2879552 treatment resulted in potent anti-proliferative growth effects in 19 of 25 AML cell lines representing a range of AML subtypes. Treating for longer time periods revealed sensitivity in all AML cell lines. AML blast colony forming ability was also inhibited in 4 of 5 bone marrow samples derived from primary AML patient samples [1].
In vivo: After 17 days of GSK2879552 treatment, control mice had 80% GFP+ cells in the bone marrow whereas treated mice had only 2.8% GFP positive cells, and the treated animals survived weeks beyond control mice [1].
Clinical trial: A phase I, open-label, multi-center, non-randomized, 2-part first time in human (FTIH) study for GSK2879552 has been condcuted to investigate the effect of GSK2879552 in subjects with relapsed/refractory small cell lung carcinoma.
Reference:
[1] Kimberly Smitheman, Monica Cusan, Yan Liu, Michael Butticello, Melissa Pappalardi, James Foley, Kelly Federowicz, Glenn Van Aller, Jiri Kasparec, Xinrong Tian, Dominic Suarez, Jess Schneck, Jeff Carson, Patrick McDevitt, Thau Ho, Charles McHugh, William Miller, Scott Armstrong, Christine Hann, Neil Johnson, Ryan G. Kruger, Helai P. Mohammad, Shekhar Kamat. Inhibition of LSD1 for the treatment of cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3513. doi:10.1158/1538-7445.AM2015-3513
| Kinase experiment [1]: | |
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LSD1 enzyme assay |
LSD1 activity was measured using a horseradish peroxidase (HRP) coupled assay with amplex red as an electron donor. The formation of product over time was measured using fluorescence intensity, Ex 531 nm and Em 595 nm, in a PerkinElmer EnVision plate reader. Final assay conditions were: 5 nM LSD1, 2.5 μM H3K4me2 peptide, 50 mM HEPES pH 7, 1 U/mL of HRP, 1 mM CHAPS, 0.03% dBSA and 10 μM amplex red. |
| Cell experiment [1]: | |
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Cell lines |
SCLC cell lines |
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Preparation method |
The solubility of this compound in DMSO is > 12.8 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 ~ 5000 nM; 10 days |
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Applications |
At the 4th day after treatment, GSK2879552 started to significantly inhibit the growth of NCI-H1417 cells in a dose-dependent manner. In a 6-day proliferation assay, the maximal growth inhibition on NCI-H1417 cells was largely below 100%, which implied the effect was predominantly cytostatic. Moreover, GSK2879552 did not cause any cytotoxic response to SCLC cell lines. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing NCI-H526 or NCI-H1417 xenografts |
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Dosage form |
1.5 mg/kg; p.o. |
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Applications |
In mice bearing NCI-H526 or NCI-H1417 xenografts, GSK2879552 significantly inhibited tumor growth with the TGI values of 57% and 83%, respectively. Meanwhile, GSK2879552 did not cause thrombocytopenia at the indicated dose. On the other hand, the results of immunohistochemistry showed that there were 98 percent of SCLC tumors with a very high expression of LSD1, implying the inhibition effect of GSK2879552 on tumor growth might be exerted by targeting LSD1. |
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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]. Mohammad HP, Smitheman KN, Kamat CD, Soong D, Federowicz KE, Van Aller GS, Schneck JL, Carson JD, Liu Y, Butticello M, Bonnette WG, Gorman SA, Degenhardt Y, Bai Y, McCabe MT, Pappalardi MB, Kasparec J, Tian X, McNulty KC, Rouse M, McDevitt P, Ho T, Crouthamel M, Hart TK, Concha NO, McHugh CF, Miller WH, Dhanak D, Tummino PJ, Carpenter CL, Johnson NW, Hann CL, Kruger RG. A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC. Cancer Cell. 2015 Jul 13;28(1):57-69. | |
| Cas No. | 1401966-69-5 | SDF | |
| 化学名 | 4-((4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid | ||
| Canonical SMILES | OC(C1=CC=C(CN2CCC(CN[C@]3([H])C[C@@]3([H])C4=CC=CC=C4)CC2)C=C1)=O | ||
| 分子式 | C23H28N2O2 | 分子量 | 364.48 |
| 溶解度 | ≥ 12.8mg/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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.7436 mL | 13.7182 mL | 27.4363 mL |
| 5 mM | 0.5487 mL | 2.7436 mL | 5.4873 mL |
| 10 mM | 0.2744 mL | 1.3718 mL | 2.7436 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