LY2109761
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
LY2109761是一种选择性的I/II型TGF-β受体(TβRI/II)小分子抑制剂,Ki值分别为38 nM和300 nM[1]。在TβRI 酶实验中,IC50值为69 nM。晶体结构显示LY2109761与TGF-βR1激酶结构域的ATP结合位点相结合。LY2109761对其它的激酶(包括Lck、Sapk2α、MKK6、Fyn和JNK3)具有较弱的抑制活性(20 μM时18-89%的抑制)[2]。
在临床前研究中,LY2109761具有潜在的抗肿瘤活性。TGF-β信号通路的调控缺失与各种恶性肿瘤的发生相关。在胰腺癌细胞中,LY2109761抑制细胞增殖、迁移和侵袭,诱导细胞凋亡。在转移性胰腺癌小鼠模型中,LY2109761与gemcitabine联合给药抑制肿瘤生长和转移[1]。在骨髓 - 单核细胞白血病细胞中,LY2109761抑制TGF-beta1的抗凋亡效应[3]。在胶质母细胞瘤(GBM)细胞系和原位颅内移植模型中,LY2109761增加放射敏感性,导致存活期的延长[4]。此外,在小鼠模型中,LY2109761减少放射诱导的肺炎和肺纤维化[5]。
参考文献:
[1]Melisi D, Ishiyama S, Sclabas GM et al. LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis. Mol Cancer Ther 2008; 7: 829-840.
[2]Li HY, McMillen WT, Heap CR et al. Optimization of a dihydropyrrolopyrazole series of transforming growth factor-beta type I receptor kinase domain inhibitors: discovery of an orally bioavailable transforming growth factor-beta receptor type I inhibitor as antitumor agent. J Med Chem 2008; 51: 2302-2306.
[3]Xu Y, Tabe Y, Jin L et al. TGF-beta receptor kinase inhibitor LY2109761 reverses the anti-apoptotic effects of TGF-beta1 in myelo-monocytic leukaemic cells co-cultured with stromal cells. Br J Haematol 2008; 142: 192-201.
[4]Zhang M, Kleber S, Rohrich M et al. Blockade of TGF-beta signaling by the TGFbetaR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma. Cancer Res 2011; 71: 7155-7167.
[5]Flechsig P, Dadrich M, Bickelhaupt S et al. LY2109761 attenuates radiation-induced pulmonary murine fibrosis via reversal of TGF-beta and BMP-associated proinflammatory and proangiogenic signals. Clin Cancer Res 2012; 18: 3616-3627.
- 1. Lili Song, Fei Wu, et al. "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway." Biogerontology. 2022 Jun;23(3):341-362. PMID: 35604508
- 2. Ying Li, Ling Liu, et al. "Silencing long non-coding RNA HNF1A-AS1 inhibits growth and resistance to TAM of breast cancer cells via the microRNA-363/SERTAD3 axis." J Drug Target. 2021 Aug;29(7):742-753. PMID: 33472456
- 3. Ján Remšík, Markéta Pícková, et al. "TGF‑β regulates Sca‑1 expression and plasticity of pre‑neoplastic mammary epithelial stem cells." Sci Rep. 2020 Jul 9;10(1):11396. PMID: 32647280
- 4. Junyi Zhao, Jun Shi, et al. "Asiaticoside inhibits TGF-β1-induced mesothelial-mesenchymal transition and oxidative stress via the Nrf2/HO-1 signaling pathway in the human peritoneal mesothelial cell line HMrSV5." Cell Mol Biol Lett. 2020 May 29;25:33. PMID: 32514269
- 5. Song Y, Chen Y, et al. "Resveratrol Suppresses Epithelial-Mesenchymal Transition in GBM by Regulating Smad-Dependent Signaling." Biomed Res Int. 2019 Apr 7;2019:1321973. PMID: 31119150
- 6. Yang H, Li W, et al. "Regulatory role of miR-18a to CCN2 by TGF-β1 signaling pathway in pulmonary injury induced by nano-SiO(2)." Environ Sci Pollut Res Int. 2017 Oct 24. PMID: 29067610
- 7. Singh SK, Fiorelli R, et al. "Post-translational Modifications of OLIG2 Regulate Glioma Invasion through the TGF-β Pathway." Cell Rep. 2016 Jul 26;16(4):950-66. PMID: 27396340
- 8. Llobet-Navas, David, et al. "The miR-424/503 cluster reduces CDC25A expression during cell cycle arrest imposed by TGFβ in mammary epithelial cells." Molecular and Cellular Biology (2014): MCB-00611. PMID: 25266660
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 441.52 |
Cas No. | 700874-71-1 |
Formula | C26H27N5O2 |
Solubility | ≥22.1 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
Chemical Name | 4-[2-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinolin-7-yl]oxyethyl]morpholine |
SDF | Download SDF |
Canonical SMILES | C1CC2=C(C(=NN2C1)C3=CC=CC=N3)C4=C5C=CC(=CC5=NC=C4)OCCN6CCOCC6 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
人类MDA PCa 2b、PC-3细胞系 |
溶解方法 |
在DMSO中的溶解度 |
反应条件 |
24 h;4 μM |
应用 |
受体激活的Smad2和Smad3的磷酸化是TGF-β1信号转导中一个重要的步骤。在rhTGF-β1处理的MDA PCa 2b细胞、PC-3细胞和PMOs裂解物中,TGF-β1诱导PC-3和PMOs,而非MDA PCa 2b细胞中Smad2的磷酸化。而且,LY2109761可以逆转rhTGF-β1诱导的Smad2的磷酸化。换句话说,LY2109761抑制PC-3和PMOs细胞中TGF-β1诱导的Smad2的激活。 |
动物实验[1]: | |
动物模型 |
雄性SCID小鼠 |
剂量 |
200 mg/kg/day;口服给药 |
应用 |
3周治疗之后,对照组的X射线分析显示有两处骨折,在荷瘤骨段减少了30%-70%的放射不透过性区域。MRI分析表明,治疗组比对照组有显著更小的肿瘤体积(p=0.012)。对照组和治疗组中荷瘤骨段的微CT分析表明,对照小鼠有显著更低的BV(p=0.00043)、BMC(p =0.000132)和BMD(p = 0.000085)。而且,治疗组的BV、BMC和BMD均恢复到正常股骨(未注射)中水平,支持了LY2109761的治疗效应。最后,骨组织形态学分析表明,LY2109761抑制PC-3诱导的破骨细胞的活化。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: [1] Wan X, Li Z G, Yingling J M, et al. Effect of transforming growth factor beta (TGF-β) receptor I kinase inhibitor on prostate cancer bone growth[J]. Bone, 2012, 50(3): 695-703. |
描述 | LY2109761是一种新型的选择性I/II型TGF-β受体(TβRI/II)抑制剂,Ki值分别为38 nM和300 nM。 | |||||
靶点 | TβRI | TβRII | ||||
IC50 | 38 nM (Ki) | 300 nM (Ki) |
质量控制和MSDS
- 批次: