LY5
目录号 : GC67706LY5 是 STAT3 的抑制剂，IC50 值为 0.5 μM。LY5 诱导细胞凋亡并抑制 STAT3 磷酸化。LY5 具有体内抗肿瘤活性，可用于癌症的研究。
Cas No.:1436382-03-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
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IC50: 0.5 μM (STAT3)[1]
LY5 is a STAT3 inhibitor with an IC50 value of 0.5 μM. LY5 induces Apoptosis and inhibits STAT3 phosphorylation. LY5 shows antitumor activity in vivo, it can be used for the research of cancer[1].
LY5 shows inhibition effects to U2OS, RH30 and RD2 cancer cells with IC50 values of 0.52, 0.55 and 1.39 μM, respectively[1].
LY5 (0.25-1 μM; 16 h) induces apoptosis and inhibits STAT3 phosphorylation in human sarcoma cancer cells[1].
LY5 (0.25-1 μM; 5 h) inhibits STAT3 phosphorylation induced by IL-6[1].
Western Blot Analysis[1]
| Cell Line: | RH30 and EW8 cell lines |
| Concentration: | 0.25-1 μM |
| Incubation Time: | 16 hours |
| Result: | Completely inhibited Tyr705 phosphorylation at 0.5 μM and dose-dependently decreased in formation of P-STAT3. |
LY5 (5 mg/kg; i.p. once daily for 21 days) inhibits breast tumor growth in vivo[1].
| Animal Model: | Nude mice with MDA-MB-231 cancer cells injection[1] |
| Dosage: | 5 mg/kg |
| Administration: | Intraperitoneal injection; 5 mg/kg; once daily; for 21 days |
| Result: | Suppressed tumor growth and significantly reduced the tumor sizes. |
[1]. Yu W, et al. Discovery of novel STAT3 small molecule inhibitors via in silico site-directed fragment-based drug design. J Med Chem. 2013 Jun 13;56(11):4402-12.
| Cas No. | 1436382-03-4 | SDF | Download SDF |
| 分子式 | C15H11N3O4S | 分子量 | 329.33 |
| 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 | 3.0365 mL | 15.1823 mL | 30.3647 mL |
| 5 mM | 0.6073 mL | 3.0365 mL | 6.0729 mL |
| 10 mM | 0.3036 mL | 1.5182 mL | 3.0365 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。
Immunogenicity of LY5 (CD45)-antigens hampers long-term engraftment following minimal conditioning in a murine bone marrow transplantation model
Stem Cells 2001;19(1):80-7.PMID:11209093DOI:10.1634/stemcells.19-1-80.
Various techniques are available for distinguishing donor from host cells evaluating the efficacy of conditioning regimen for experimental bone marrow transplantation (BMT). Techniques include the use of extracellular immunological markers, such as LY5 (CD45), and intracellular biochemical markers, such as glucose-phosphate-isomerase (Gpi). Because LY5 is an extracellular protein, the disparity between donor (LY5.1) and host (LY5.2) antigens may induce a weak immune response whereas with Gpi, no immune response is expected. This difference may be of particular concern in experimental transplantation approaches that use minimal conditioning such as low-dose total body irradiation (TBI). Such mild conditioning may not induce the immunosuppression required to overcome host rejection of LY5 disparate cells. To compare the relative engraftment of LY5.1 and Gpi-1(a) donor marrow, B6 (Gpi-1(b)/LY5.2) mice were irradiated with low-level TBI (0-6 Gy) and transplanted with several bone marrow (BM) doses (2 x 10(6)-5 x 10(7) cells). At 8, 26, and 52 weeks post-BMT, the level of donor engraftment was measured using flow cytometry (LY5) or Gpi-electrophoresis. Lower engraftment levels were found in mice transplanted with LY5 congenic BM in groups given low-dose TBI (< or = 4 Gy) and/or low doses of BM cells (BMC) (2 x 10(6)). However, when higher TBI or BMC doses were used, similar engraftment levels were found, suggesting sufficient immune suppression to allow equal engraftment of both sources of BM. These data suggest that even a minor phenotypic disparity between donor and host, such as LY5, may necessitate high-dose TBI to prevent rejection. The combination of low-dose TBI or other nonmyeloablative conditioning strategies with small numbers of BMC may lead to reduced engraftment when extracellular immunological markers such as LY5 are used for transplantation studies. Therefore, small immunological differences must be considered when using the LY5 marker for engraftment.
A novel small molecular STAT3 inhibitor, LY5, inhibits cell viability, cell migration, and angiogenesis in medulloblastoma cells
J Biol Chem 2015 Feb 6;290(6):3418-29.PMID:25313399DOI:10.1074/jbc.M114.616748.
Signal transducers and activators of transcription 3 (STAT3) signaling is persistently activated and could contribute to tumorigenesis of medulloblastoma. Numerous studies have demonstrated that inhibition of the persistent STAT3 signaling pathway results in decreased proliferation and increased apoptosis in human cancer cells, indicating that STAT3 is a viable molecular target for cancer therapy. In this study, we investigated a novel non-peptide, cell-permeable small molecule, named LY5, to target STAT3 in medulloblastoma cells. LY5 inhibited persistent STAT3 phosphorylation and induced apoptosis in human medulloblastoma cell lines expressing constitutive STAT3 phosphorylation. The inhibition of STAT3 signaling by LY5 was confirmed by down-regulating the expression of the downstream targets of STAT3, including cyclin D1, bcl-XL, survivin, and micro-RNA-21. LY5 also inhibited the induction of STAT3 phosphorylation by interleukin-6 (IL-6), insulin-like growth factor (IGF)-1, IGF-2, and leukemia inhibitory factor in medulloblastoma cells, but did not inhibit STAT1 and STAT5 phosphorylation stimulated by interferon-γ (IFN-γ) and EGF, respectively. In addition, LY5 blocked the STAT3 nuclear localization induced by IL-6, but did not block STAT1 and STAT5 nuclear translocation mediated by IFN-γ and EGF, respectively. A combination of LY5 with cisplatin or x-ray radiation also showed more potent effects than single treatment alone in the inhibition of cell viability in human medulloblastoma cells. Furthermore, LY5 demonstrated a potent inhibitory activity on cell migration and angiogenesis. Taken together, these findings indicate LY5 inhibits persistent and inducible STAT3 phosphorylation and suggest that LY5 is a promising therapeutic drug candidate for medulloblastoma by inhibiting persistent STAT3 signaling.
A novel small molecule STAT3 inhibitor, LY5, inhibits cell viability, colony formation, and migration of colon and liver cancer cells
Oncotarget 2016 Mar 15;7(11):12917-26.PMID:26883202DOI:10.18632/oncotarget.7338.
Signal Transducer and Activator of Transcription 3 (STAT3) is persistently activated in human liver and colon cancer cells and is required for cancer cell viability, survival and migration. Therefore, inhibition of STAT3 signaling may be a viable therapeutic approach for these two cancers. We recently designed a non-peptide small molecule STAT3 inhibitor, LY5, using in silico site-directed Fragment-based drug design (FBDD). The inhibitory effect on STAT3 phosphorylation, cell viability, migration and colony forming ability by LY5 were examined in human liver and colon cancer cells. We demonstrated that LY5 inhibited constitutive Interleukin-6 (IL-6)-induced STAT3 phosphorylation, STAT3 nuclear translocation, decreased STAT3 downstream targeted gene expression and induced apoptosis in liver and colon cancer cells. LY5 had little effect on STAT1 phosphorylation mediated by IFN-γ. Inhibition of persistent STAT3 phosphorylation by LY5 also inhibited colony formation, cell migration, and decreased the viability of liver cancer and colon cancer cells. Furthermore, LY5 inhibited STAT3 phosphorylation and suppressed colon tumor growth in a mouse model in vivo. Our results suggest that LY5 is a potent STAT3 inhibitor and may be a potential drug candidate for liver and colon cancer therapy.
Target specificity, in vivo pharmacokinetics, and efficacy of the putative STAT3 inhibitor LY5 in osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma
PLoS One 2017 Jul 27;12(7):e0181885.PMID:28750090DOI:10.1371/journal.pone.0181885.
Background: STAT3 is a transcription factor involved in cytokine and receptor kinase signal transduction that is aberrantly activated in a variety of sarcomas, promoting metastasis and chemotherapy resistance. The purpose of this work was to develop and test a novel putative STAT3 inhibitor, LY5. Methods and findings: An in silico fragment-based drug design strategy was used to create LY5, a small molecule inhibitor that blocks the STAT3 SH2 domain phosphotyrosine binding site, inhibiting homodimerization. LY5 was evaluated in vitro demonstrating good biologic activity against rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma cell lines at high nanomolar/low micromolar concentrations, as well as specific inhibition of STAT3 phosphorylation without effects on other STAT3 family members. LY5 exhibited excellent oral bioavailability in both mice and healthy dogs, and drug absorption was enhanced in the fasted state with tolerable dosing in mice at 40 mg/kg BID. However, RNAi-mediated knockdown of STAT3 did not phenocopy the biologic effects of LY5 in sarcoma cell lines. Moreover, concentrations needed to inhibit ex vivo metastasis growth using the PuMA assay were significantly higher than those needed to inhibit STAT3 phosphorylation in vitro. Lastly, LY5 treatment did not inhibit the growth of sarcoma xenografts or prevent pulmonary metastasis in mice. Conclusions: LY5 is a novel small molecule inhibitor that effectively inhibits STAT3 phosphorylation and cell proliferation at nanomolar concentrations. LY5 demonstrates good oral bioavailability in mice and dogs. However LY5 did not decrease tumor growth in xenograft mouse models and STAT3 knockdown did not induce concordant biologic effects. These data suggest that the anti-cancer effects of LY5 identified in vitro were not mediated through STAT3 inhibition.
Analysis of LY5 chromosome 1 position using allelic differences and recombinant inbred mice
Eur J Immunogenet 1991 Jun;18(3):155-63.PMID:1834169DOI:10.1111/j.1744-313x.1991.tb00015.x.
Differences between the mouse Ly5a and Ly5b alleles can be distinguished on the basis of polymerase chain reaction (PCR)-restriction enzyme analysis and differential monoclonal antibody reactivities. To more precisely map the LY5 gene on the mouse chromosome 1, analytical DNA and protein tests were performed on recombinant inbred strains of mice prepared from SJL/J (Ly5a) and BALB/cke (Ly5b) progenitor strains. Each recombinant inbred strain was characterized to determine whether it carried the Ly5a or Ly5b allele. Both assays, DNA-PCR and protein-immunofluorescence, yielded identical results for each strain examined. Placement of the LY5 gene with respect to other characterized markers of mouse chromosome 1 for these recombinant inbred mouse strains shows a gene order of Idh-1:Ity:Pep3:[LY5, Cfh].