PTC-209
目录号 : GC15725
PTC-209 是一种小分子化合物，可选择性抑制 BMI-1，在 HT1080 细胞中的 IC50 为 0.5μM，是一种很有前途的抗癌药物在体外，PTC-209 以 0.1 到 10μM 之间的剂量处理人结直肠癌细胞，以剂量依赖性方式降低 BMI-1 蛋白水平，同时减少细胞生长。
Cas No.:315704-66-6
Sample solution is provided at 25 µL, 10mM.
PTC-209, a low-molecular-weight compound that selectively inhibits BMI-1 with IC50 for 0.5μM in HT1080 cells, is a promising anticancer[1,2]
In vitro, PTC-209 treats human colorectal cancer cells with doses between 0.1 and 10μM reduced BMI-1 protein levels in a dose-dependent manner with a concomitant reduction in cell growth[1]. PTC-209 causes a concentration- and time-dependent decrease in the cellular viability of lung cancer cells (LNM35 and A549), breast cancer cells (MDA-MB-231 and T47D), and colon cancer cells (HT-29, HCT8/S11, and HCT-116)[2]. Treatment with PTC-209 significantly decreased viable cell numbers in human multiple myeloma (MM) cell lines, induced a G1 cell cycle arrest, promoted apoptosis and demonstrated synergistic activity with pomalidomide and carfilzomib. In the MM microenvironment, PTC-209 impaired tube formation, impaired osteoclast development and decreased osteoblast formation in a dose-dependent manner (P < 0.01 at 1μM, respectively). Therapeutic targeting of BMI-1 by PTC-209 is a promising novel therapeutic intervention for MM[3]
PTC-209 combined with palbociclib inhibit tumor cell proliferation, sphere and colony formation, migration, and in vivo tumor formation[4]. PTC-209 administration significantly reduced tumor growth in a HNSCC xenograft model by Bmi1 inhibition and impaired cell proliferation in vivo[5]. PTC-209 significantly attenuates the glioblastoma growth in a murine orthotopic xenograft model[6]
References:
[1].Kreso A, van Galen P, et al. Self-renewal as a therapeutic target in human colorectal cancer. Nat Med. 2014;20(1):29-36.
[2].Sulaiman S, Arafat K, et al. PTC-209 Anti-Cancer Effects Involved the Inhibition of STAT3 Phosphorylation. Front Pharmacol. 2019;10:1199. Published 2019 Oct 21.
[3].Bolomsky A, Schlangen K, et al. Targeting of BMI-1 with PTC-209 shows potent anti-myeloma activity and impairs the tumour microenvironment. J Hematol Oncol. 2016;9:17. Published 2016 Mar 2.
[4]. Elango R, Vishnubalaji R, et al. Concurrent targeting of BMI1 and CDK4/6 abrogates tumor growth in vitro and in vivo. Sci Rep. 2019;9(1):13696. Published 2019 Sep 23.
[5].Wang Q, Li Z, et al. Pharmacological inhibition of Bmi1 by PTC-209 impaired tumor growth in head neck squamous cell carcinoma. Cancer Cell Int. 2017;17:107. Published 2017 Nov 21.
[6].Kong Y, Ai C, et al. Targeting of BMI-1 with PTC-209 inhibits glioblastoma development. Cell Cycle. 2018;17(10):1199-1211
PTC-209 是一种小分子化合物，可选择性抑制 BMI-1，在 HT1080 细胞中的 IC50 为 0.5μM，是一种很有前途的抗癌药物[1,2]
在体外，PTC-209 以 0.1 到 10μM 之间的剂量处理人结直肠癌细胞，以剂量依赖性方式降低 BMI-1 蛋白水平，同时减少细胞生长[1]。 PTC-209 导致肺癌细胞（LNM35 和 A549）、乳腺癌细胞（MDA-MB-231 和 T47D）和结肠癌细胞（HT-29、HCT8/ S11 和 HCT-116)[2]。用 PTC-209 处理可显着降低人多发性骨髓瘤 (MM) 细胞系中的活细胞数量，诱导 G1 细胞周期停滞，促进细胞凋亡，并证明与泊马度胺和卡非佐米具有协同活性。在 MM 微环境中，PTC-209 以剂量依赖性方式损害管形成、损害破骨细胞发育和减少成骨细胞形成（P <；1μM 时分别为 0.01）。 PTC-209 对 BMI-1 的治疗靶向是一种很有前途的 MM 新型治疗干预措施[3]
PTC-209 联合 palbociclib 可抑制肿瘤细胞增殖、球体和集落形成、迁移以及体内肿瘤形成[4]。 PTC-209 给药通过 Bmi1 抑制和体内细胞增殖受损显着降低了 HNSCC 异种移植模型中的肿瘤生长[5]。 PTC-209 显着减弱小鼠原位异种移植模型中的胶质母细胞瘤生长[6]
| Cell experiment [1]: | |
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Cell lines |
various cancer cell lines: lung (LNM35, A549), breast (MDA-MB-231 and T47D), and colon (HT-29, HCT-116, and HCT8/S11) |
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Preparation Method |
Cells were seeded at a density of 5000 cells/well into 96-well plates. After 24h, cells were treated for another 24, 48, and 72h with increasing concentrations of PTC-209 (0.01-10 µM) in triplicate. Control cultures were treated with 0.1% DMSO (the drug vehicle). |
|
Reaction Conditions |
0.01-10µM PTC-209 for 24, 48, and 72h |
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Applications |
PTC-209 induced a concentration- and time-dependent decrease in the cellular viability of all cell lines tested. Lung cancer cells (LNM35 and A549) showed a higher sensitivity to PTC-209 treatment compared with breast (MDA-MB-231) and colon (HT-29) cancer cells. |
| Animal experiment [2]: | |
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Animal models |
female nude mice, four to six weeks old |
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Preparation Method |
MDA-MB-231 cells were exposed to PTC-209, palbociclib, or combination of the two inhibitors at 5.0µM for 72h. Cells were then trypsinized, washed with PBS, and 2×106 cells were subcutaneously injected into the right left frank of female nude mice in a 100µL mixture (1:1 v/v of PBS/matrigel). The animals were monitored twice weekly and tumor volume was measured using caliper. |
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Dosage form |
MDA-MB-231 cells were exposed to drugs at 5.0µM for 72h |
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Applications |
PTC-209 and palbociclib significantly inhibit the growth of tumor, and combination of both drugs was more efficacious in inhibiting MDA-MB-231 tumor growth in vivo. PTC-209 and palbociclib treatments restricted the invasiveness of MDA-MB-231 cells, while combination group exhibited the most profound restricted invasion of tumor cells compared to other treatment groups and control. |
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References: [1]. Sulaiman S, Arafat K, et al. PTC-209 Anti-Cancer Effects Involved the Inhibition of STAT3 Phosphorylation. Front Pharmacol. 2019;10:1199. Published 2019 Oct 21. [2]. Elango R, Vishnubalaji R, et al. Concurrent targeting of BMI1 and CDK4/6 abrogates tumor growth in vitro and in vivo. Sci Rep. 2019;9(1):13696. Published 2019 Sep 23. |
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| Cas No. | 315704-66-6 | SDF | |
| 化学名 | N-(2,6-dibromo-4-methoxyphenyl)-4-(2-methylimidazo[1,2-a]pyrimidin-3-yl)-1,3-thiazol-2-amine | ||
| Canonical SMILES | CC1=C(N2C=CC=NC2=N1)C3=CSC(=N3)NC4=C(C=C(C=C4Br)OC)Br | ||
| 分子式 | C17H13Br2N5OS | 分子量 | 495.19 |
| 溶解度 | ≥ 24.75mg/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 | 2.0194 mL | 10.0971 mL | 20.1943 mL |
| 5 mM | 0.4039 mL | 2.0194 mL | 4.0389 mL |
| 10 mM | 0.2019 mL | 1.0097 mL | 2.0194 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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