T-3775440 hydrochloride
目录号 : GC33038
T-3775440 HCl is an irreversible LSD1 inhibitor that is highly selective for LSD1 relative to other monoamine oxidases (e.g., MAO-A and MAO-B), with an IC50 value of 2.1 nmol/L.
Cas No.:1422535-52-1
Sample solution is provided at 25 µL, 10mM.
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T-3775440 HCl is an irreversible LSD1 inhibitor that is highly selective for LSD1 relative to other monoamine oxidases (e.g., MAO-A and MAO-B), with an IC50 value of 2.1 nmol/L.
T-3775440 treatment enforces transdifferentiation of erythroid/megakaryocytic lineages into granulomonocytic-like lineage cells. T-3775440 disrupts the interaction between LSD1 and growth factor-independent 1B (GFI1B), a transcription factor critical for the differentiation processes of erythroid and megakaryocytic lineage cells. 48-hour T-3775440 treatment induces cell-cycle arrest and apoptosis in AEL (TF-1a, HEL92.1.7) and AMKL cell lines (CMK11-5, M07e). T-3775440 treatment increases the G1 and sub-G1 phase populations in TF-1a and CMK11-5 cells[1].
T-3775440 exerts tumor growth suppression in in vivo mouse xenograft models of AML. In mice, T-3775440 treatment results in a transient reduction in platelets, followed by a significant rebound. There is no obvious effect on red blood cell counts following a single administration. T-3775440 also exhibits potent antitumor effects in an additional AEL model of HEL 92.1.7 and an AMKL model of CMK11-5, possessing profound anti-AEL and anti-AMKL activity[1].
[1] Ishikawa Y, et al. Mol Cancer Ther. 2017, 16(2):273-284. [2] Ishikawa Y, et al. Oncogenesis. 2017, 6(9):e377.
Cell experiment: | The human leukemia cell lines TF-1a, HEL92.1.7, CMK11-5 and M07e are used. All cells are grown in RPMI1640 plus 10% FBS and maintained in a humidified incubator at 37°C and 5% CO2. To assess cell proliferation and viability in human leukemia cell lines, compounds (e.g T-3775440) are added with different concentrations (T-3775440: 0, 10, 50 nM) at 24 h after cell seeding. After the incubation period, cells are lysed with CellTiter-Glo, and luminescent signals are detected using an ARVO MX1420 microplate reader. For cell-cycle analysis, cells are fixed overnight with 70% ethanol. Fixed cells are stained with propidium iodide and analyzed on a FACSCalibur or FACSVerse flow cytometer[1]. |
Animal experiment: | Mice[1]Female C.B17/Icr-scid/scid Jcl mice are used and maintained under specific pathogen-free conditions. AML cells (2×106 cells) in Matrigel are inoculated subcutaneously into the left flanks of 6- to 7-week-old mice (day 0). Mice are randomized when the mean tumor volume reached approximately 150 to 350 mm3. Subsequently, mice are administrated with vehicle or T-3775440 single doses ranging from 3 to 30 mg/kg once daily on 5 days on/2 days off schedule for 2 weeks. Twice weekly, tumors are measured with vernier calipers, and tumor volumes are calculated[1]. |
References: [1]. Ishikawa Y, et al. A Novel LSD1 Inhibitor T-3775440 Disrupts GFI1B-Containing Complex Leading to Transdifferentiation and Impaired Growth of AML Cells. Mol Cancer Ther. 2017 Feb;16(2):273-284. | |
| Cas No. | 1422535-52-1 | SDF | |
| Canonical SMILES | O=C(NC1=CC=C([C@@H]2C[C@H]2NCC3CC3)C=C1)C4=CN(C)N=C4.Cl | ||
| 分子式 | C18H23ClN4O | 分子量 | 346.85 |
| 溶解度 | DMSO : ≥ 30.18 mg/mL (87.01 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 | 2.8831 mL | 14.4155 mL | 28.8309 mL |
| 5 mM | 0.5766 mL | 2.8831 mL | 5.7662 mL |
| 10 mM | 0.2883 mL | 1.4415 mL | 2.8831 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%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet