TD52
目录号 : GC62191
A derivative of erlotinib
Cas No.:1798328-24-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
TD52 is a derivative of the EGFR tyrosine kinase inhibitor erlotinib .1 It decreases the viability of HA22T, Hep3B, PLC/PRF/5, and SK-HEP-1 hepatocellular carcinoma cells (IC50s = 0.9, 0.9, 0.8, and 1.2 ?M, respectively). TD52 induces apoptosis in a variety of cancer cells, including HA22T and Hep3B hepatocellular carcinoma and HCC1937 and MDA-MB-231 triple-negative breast cancer cells in a concentration-dependent manner.1,2 TD52 (10 mg/kg per day) increases intratumoral protein phosphatase 2A (PP2A) activity, reduces intratumoral cancerous inhibitor of PP2A (CIP2A) and phosphorylated Akt levels, and reduces tumor growth in a PLC/PRF/5 mouse xenograft model.1
1.Yu, H.-C., Hung, M.-H., Chen, Y.-L., et al.Erlotinib derivative inhibits hepatocellular carcinoma by targeting CIP2A to reactivate protein phosphatase 2ACell Death Dis.5(7)e1359(2014) 2.Liu, C.-Y., Huang, T.-T., Huang, C.-T., et al.EGFR-independent Elk1/CIP2A signalling mediates apoptotic effect of an erlotinib derivative TD52 in triple-negative breast cancer cellsEur. J. Cancer72112-123(2017)
| Cas No. | 1798328-24-1 | SDF | |
| 分子式 | C24H16N4 | 分子量 | 360.41 |
| 溶解度 | 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 | 2.7746 mL | 13.8731 mL | 27.7462 mL |
| 5 mM | 0.5549 mL | 2.7746 mL | 5.5492 mL |
| 10 mM | 0.2775 mL | 1.3873 mL | 2.7746 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。
EGFR-independent Elk1/CIP2A signalling mediates apoptotic effect of an erlotinib derivative TD52 in triple-negative breast cancer cells
Eur J Cancer 2017 Feb;72:112-123.PMID:28027514DOI:10.1016/j.ejca.2016.11.012.
Objectives: Cancerous inhibitor of protein phosphatase 2A (CIP2A) has emerged as a therapeutic determinant mediating the anti-cancer effects of several new agents. We investigated the efficacy and mechanism of TD52, an erlotinib derivative with minimal p-EGFR inhibition but significant CIP2A downregulation, in triple-negative breast cancer (TNBC) cells. Methods: TNBC lines were used for in vitro studies. Cell apoptosis was examined by flow cytometry and Western blot. Signal transduction pathways in cells were assessed by Western blot. In vivo efficacy of TD52 was tested in xenograft nude mice. Results: We explored the CIP2A mRNA expression in a publically available database and found that higher levels of CIP2A mRNA is associated with worse recurrence-free survival in patients with TNBC. TD52-enhanced apoptosis accompanied with CIP2A downregulation and CIP2A overexpression protected cells from TD52-mediated apoptosis. The activity of protein phosphatase 2A (PP2A) was also increased in TD52-treated cells. TD52-induced apoptosis and p-Akt downregulation was attenuated by PP2A antagonist okadaic acid. Furthermore, TD52 indirectly downregulated CIP2A transcription via disturbing the binding of Elk1 to the CIP2A promoter. Importantly, TD52 showed anti-tumour activity in mice bearing TNBC xenograft tumours and downregulated CIP2A and p-Akt in these xenografted tumours. Interestingly, higher Elk1 mRNA expression was also associated with worse recurrence-free survival in TNBC patients by Kaplan-Meier survival analysis. Conclusion: Our findings indicated that EGFR-independent pharmacological modulation on Elk1/CIP2A signalling mediates the apoptotic effect of TD52 in TNBC cells, suggesting the potential therapeutic strategy.
Erlotinib derivative inhibits hepatocellular carcinoma by targeting CIP2A to reactivate protein phosphatase 2A
Cell Death Dis 2014 Jul 31;5(7):e1359.PMID:25077545DOI:10.1038/cddis.2014.325.
Protein phosphatase 2A (PP2A) is a tumor suppressor, which is functionally defective in various cancers. Previously, we found that PP2A activity determined the anticancer effect of bortezomib and erlotinib in hepatocellular carcinoma (HCC) cells. Here, we tested a novel erlotinib derivative, TD52, in four HCC cell lines, PLC5, Huh-7, Hep3B and Sk-Hep1. Using MTT and flow cytometry, we showed that TD52 had more potent apoptotic effects than erlotinib in HCC cells. TD52-induced apoptosis was associated with dose- and time- dependent reactivation of PP2A and downregulation of cancerous inhibitor of protein phosphatase 2A (CIP2A) and p-Akt. Inhibition of PP2A or ectopic expression of CIP2A or Akt in PLC5 cells abolished the effects of TD52. Furthermore, we demonstrated that TD52 affected the binding of Elk-1 to the proximal promoter of the CIP2A gene, thus downregulating transcription of CIP2A. Importantly, TD52-induced tumor inhibition was associated with reactivation of PP2A and downregulation of CIP2A and p-Akt in vivo. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A determines the apoptotic effect induced by TD52. Our findings disclose the therapeutic mechanism of this novel targeted agent, and suggest the therapeutic potential and feasibility of developing PP2A enhancers as a novel anticancer strategy.
Specific changes in the proteomic pattern produced by the BRCA1-Ser1841Asn missense mutation
Int J Biochem Cell Biol 2007;39(1):220-6.PMID:17005433DOI:10.1016/j.biocel.2006.08.005.
BRCA1 is a nuclear phosphoprotein that plays a key role in many cell functions, including DNA repair, control of transcription, recombination and cell cycle homeostasis. Inherited missense mutations in the BRCA1 gene may predispose to breast and ovarian cancer, but the molecular mechanisms underlying BRCA1-induced tumorigenesis are still to be elucidated. Functional studies performed so far have contributed to the characterization of several single-nucleotide variants, mostly located at the BRCT domain, but very little is known about modifications in the protein pattern occurring in cells carrying these mutations. To shed more light in the molecular events triggered by missense mutations affecting breast cancer susceptibility genes, we have analyzed the whole cell proteome of stably transfected HeLa cell lines bearing three distinct single aminoacid changes in the BRCA1 protein (Ser1841Asn, Met1775Arg and Trp1837Arg) by means of liquid chromatography coupled to tandem-mass spectrometry. The results show that the Met1775Arg and the Trp1837Arg do not produce significant changes in the proteomic pattern compared to cells transfected with the wild-type BRCA1 cDNA. On the other hand, a different profile is detected in the BRCA1 Ser1841Asn-bearing cell line. In this particular subset, our attention has been focused on two proteins--the tumor protein D52 (TD52) and the folate receptor alpha (FOL1)--whose expression has been already reported to be upregulated in breast cancer, as well as in other tumors. Our findings indicate that Ser1841Asn BRCA1 mutation is able to activate specific protein pathways that are not triggered by other single aminoacid changes and pinpoint to the role TD52 and FOL1 as potential markers in breast cancer patients carrying this particular BRCA1 gene alteration.