LY-2109761

• CAT Number: I004628
• CAS Number: 700874-71-1
• Molecular Formula: C26H27N5O2
• Molecular Weight: 441.535
• Purity: ≥95%
• Target: TGF-βR1(ALK5)
• Solubility: 10 mM in DMSO
• Storage: 3 years -20C powder
• IC50: 38 nM/300 nM(Ki, TβRI/II) [1]
• IUPAC Name: 4-[2-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinolin-7-yl]oxyethyl]morpholine
• InChI: InChI=1S/C26H27N5O2/c1-2-9-27-22(4-1)26-25(24-5-3-11-31(24)29-26)21-8-10-28-23-18-19(6-7-20(21)23)33-17-14-30-12-15-32-16-13-30/h1-2,4,6-10,18H,3,5,11-17H2
• InChIKey: IHLVSLOZUHKNMQ-UHFFFAOYSA-N
• SMILES: C1CC2=C(C(=NN2C1)C3=CC=CC=N3)C4=C5C=CC(=CC5=NC=C4)OCCN6CCOCC6

LY2109761(CAT: I004628) is a novel selective inhibitor that targets both type I and type II receptors of the transforming growth factor-beta (TGF-β) pathway. It acts as a dual inhibitor of TGF-β receptor type I (TβRI) and type II (TβRII) with Ki values of 38 nM and 300 nM, respectively. By inhibiting these receptors, LY2109761 negatively affects the phosphorylation of Smad2, a downstream effector of the TGF-β signaling pathway. This inhibition of TGF-β signaling can have therapeutic implications, as dysregulation of the TGF-β pathway is implicated in various diseases, including cancer, fibrosis, and immune disorders. LY2109761 has been studied for its potential as an anti-cancer agent and for its ability to modulate TGF-β signaling in other pathological conditions.

Reference

1:LY2109761 enhances cisplatin antitumor activity in ovarian cancer cells. Gao Y, Shan N, Zhao C, Wang Y, Xu F, Li J, Yu X, Gao L, Yi Z.Int J Clin Exp Pathol. 2015 May 1;8(5):4923-32. eCollection 2015. PMID: 26191185 Free PMC Article
2:LY2109761 inhibits metastasis and enhances chemosensitivity in osteosarcoma MG-63 cells. Ren XF, Mu LP, Jiang YS, Wang L, Ma JF.Eur Rev Med Pharmacol Sci. 2015 Apr;19(7):1182-90. PMID: 25912577 Free Article
3:LY2109761 attenuates radiation-induced pulmonary murine fibrosis via reversal of TGF-β and BMP-associated proinflammatory and proangiogenic signals. Flechsig P, Dadrich M, Bickelhaupt S, Jenne J, Hauser K, Timke C, Peschke P, Hahn EW, Gröne HJ, Yingling J, Lahn M, Wirkner U, Huber PE.Clin Cancer Res. 2012 Jul 1;18(13):3616-27. doi: 10.1158/1078-0432.CCR-11-2855. Epub 2012 Apr 30. PMID: 22547771 Free Article
4:Blockade of TGF-β signaling by the TGFβR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma. Zhang M, Kleber S, Röhrich M, Timke C, Han N, Tuettenberg J, Martin-Villalba A, Debus J, Peschke P, Wirkner U, Lahn M, Huber PE.Cancer Res. 2011 Dec 1;71(23):7155-67. doi: 10.1158/0008-5472.CAN-11-1212. Epub 2011 Oct 17. PMID: 22006998 Free Article
5:Trimodal glioblastoma treatment consisting of concurrent radiotherapy, temozolomide, and the novel TGF-β receptor I kinase inhibitor LY2109761. Zhang M, Herion TW, Timke C, Han N, Hauser K, Weber KJ, Peschke P, Wirkner U, Lahn M, Huber PE.Neoplasia. 2011 Jun;13(6):537-49. PMID: 21677877 Free PMC Article
6:Outgrowth of drug-resistant carcinomas expressing markers of tumor aggression after long-term TβRI/II kinase inhibition with LY2109761. Connolly EC, Saunier EF, Quigley D, Luu MT, De Sapio A, Hann B, Yingling JM, Akhurst RJ.Cancer Res. 2011 Mar 15;71(6):2339-49. doi: 10.1158/0008-5472.CAN-10-2941. Epub 2011 Jan 31. PMID: 21282335 Free PMC Article
7:TGF-beta receptor kinase inhibitor LY2109761 reverses the anti-apoptotic effects of TGF-beta1 in myelo-monocytic leukaemic cells co-cultured with stromal cells. Xu Y, Tabe Y, Jin L, Watt J, McQueen T, Ohsaka A, Andreeff M, Konopleva M.Br J Haematol. 2008 Jun;142(2):192-201. doi: 10.1111/j.1365-2141.2008.07130.x. Epub 2008 May 19. PMID: 18492113
8:LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis. Melisi D, Ishiyama S, Sclabas GM, Fleming JB, Xia Q, Tortora G, Abbruzzese JL, Chiao PJ.Mol Cancer Ther. 2008 Apr;7(4):829-40. doi: 10.1158/1535-7163.MCT-07-0337. PMID: 18413796 Free PMC Article