LY-2109761

For research use only. Not for therapeutic Use.

  • CAT Number: I004628
  • CAS Number: 700874-71-1
  • Molecular Formula: C26H27N5O2
  • Molecular Weight: 441.535
  • Purity: ≥95%
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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.


Catalog Number I004628
CAS Number 700874-71-1
Synonyms

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

Molecular Formula C26H27N5O2
Purity ≥95%
Target Autophagy
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
Reference

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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<br />
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<br />
3:LY2109761 attenuates radiation-induced pulmonary murine fibrosis via reversal of TGF-&beta; and BMP-associated proinflammatory and proangiogenic signals. Flechsig P, Dadrich M, Bickelhaupt S, Jenne J, Hauser K, Timke C, Peschke P, Hahn EW, Gr&ouml;ne 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<br />
4:Blockade of TGF-&beta; signaling by the TGF&beta;R-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma. Zhang M, Kleber S, R&ouml;hrich 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<br />
5:Trimodal glioblastoma treatment consisting of concurrent radiotherapy, temozolomide, and the novel TGF-&beta; 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<br />
6:Outgrowth of drug-resistant carcinomas expressing markers of tumor aggression after long-term T&beta;RI/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<br />
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<br />
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

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