LY2109761是一种小分子抑制剂，选择性靶向I型和II型TGF-β受体((TβRI/II))，Ki分别为38 nM和300nM[1]。它在TβRI酶法测定中给出69 nM的IC50值[2]。晶体结构显示LY2109761与TGF-β R1激酶结构域的ATP结合位点结合[2]。据报道，其他激酶的抑制活性较弱，包括Lck、Sapk2α、MKK6、Fyn和JNK 3(20M时抑制率为18–89%)[2]。

   LY2109761在临床前研究中显示出潜在的抗肿瘤活性。TGF-β信号通路的异常与多种恶性肿瘤相关。LY2109761抑制胰腺癌细胞的增殖、迁移和侵袭，并诱导其凋亡[1]。当与吉西他滨联合使用时，它可以抑制转移性胰腺癌小鼠模型中的肿瘤生长和转移[1]。它还抑制了TGF-β1在骨髓-单核细胞白血病细胞中的抗凋亡作用[3]。GBM细胞系和原位颅内模型的结果表明，LY2109761增加了放射敏感性，并延长了胶质母细胞瘤的生存期[4]。此外，LY2109761减少了小鼠模型中辐射诱导的肺炎和肺纤维化[5]。

产品性质：

Cas No.：700874-71-1

化学名： 4-[2-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinolin-7-yl]oxyethyl]morpholine

Canonical SMILES：C1CC2=C(C(=NN2C1)C3=CC=CC=N3)C4=C5C=CC(=CC5=NC=C4)OCCN6CCOCC6

分子式：C26H27N5O2

分子量：441.52

溶解度：≥ 22.1mg/mL in DMSO

储存条件：Store at -20°C

注意事项：

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References:

[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] [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.