LY2109761 | CAS#700874-71-1 | TGF-β inhibitor| MedKoo

MedKoo Cat#: 401550 | Name: LY2109761

Description:

WARNING: This product is for research use only, not for human or veterinary use.

LY2109761 is a TGF-β receptor I/II inhibitor. LY2109761 promoted apoptosis, decreased the phosphorylation of Smad2 and Smad3, and suppressed TGF-β1. LY2109761 reduces TGF-β1-induced collagen production and contraction in hypertrophic scar fibroblasts. LY2109761 enhances cisplatin antitumor activity in ovarian cancer cells. LY2109761 attenuates radiation-induced pulmonary murine fibrosis via reversal of TGF-β and BMP-associated proinflammatory and proangiogenic signals.

Chemical Structure

LY2109761

CAS#700874-71-1

Theoretical Analysis

MedKoo Cat#: 401550

Name: LY2109761

CAS#: 700874-71-1

Chemical Formula: C26H27N5O2

Exact Mass: 441.2165

Molecular Weight: 441.52

Elemental Analysis: C, 70.73; H, 6.16; N, 15.86; O, 7.25

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
50mg	USD 350.00	Ready to ship
100mg	USD 550.00	Ready to ship
200mg	USD 950.00	Ready to ship
500mg	USD 1,850.00	Ready to Ship
1g	USD 2,950.00	Ready to ship
2g	USD 4,950.00	Ready to ship

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Related CAS #

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Synonym

LY2109761; LY 2109761; LY-2109761;

IUPAC/Chemical Name

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

InChi Key

IHLVSLOZUHKNMQ-UHFFFAOYSA-N

InChi Code

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

SMILES Code

N1(CCOC2=CC=C3C(C4=C(CCC5)N5N=C4C6=NC=CC=C6)=CC=NC3=C2)CCOCC1

Appearance

White solid powder

Purity

>98%

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>5 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB50908

View CoA: current batch, Lot#CRB70328

QC Data

View QC data: current batch, Lot#CRB50908

View QC data: current batch, Lot#CRB70328

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

LY2109761 is an orally active, selective TGF-β receptor type I/II inhibitor with Kis of 38 nM and 300 nM, respectively.

In vitro activity:

The present study investigated the effect and the underlying mechanisms of LY2109761 treatment on keloid-derived fibroblasts. LY2109761 treatment at two concentrations (5 and 10 μM) inhibited the expression of key extracellular matrix factors secreted by fibroblasts and responsible for promoting keloid development. This included TGF-β, collagens I and III, fibronectin, and MMP-1, and MMP-3, at both mRNA and protein levels. Reference: Anal Cell Pathol (Amst). 2021; 2021: 8883427. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889383/

In vivo activity:

The drug was intraperitoneally administered (Figure 7E), and the mice were sacrificed on the 31st day. Tumor volume was clearly reduced in the LY2109761 treatment group and was accompanied by decreased Ki-67, TGF-β and CD34 staining (Figure 7F). Then, the tumors were excised and subjected to RNA-seq. All groups had similar expression density distributions. Hierarchical clustering showed that the same processing groups had the closest distances (Figure 7G). The expression profiles of clusters determined by Mfuzz showed that the genes of mesenchymal subtype-related micNETs were downregulated by LY2109761 (Figure 7H and Table S11). Reference: Theranostics. 2018; 8(17): 4733–4749. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160778/

	Solvent	mg/mL	mM
Solubility
	DMSO	12.0	27.11
	Ethanol	2.0	4.53

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 441.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Wang X, Gu C, Shang F, Jin R, Zhou J, Gao Z. Inhibitory Effect of the LY2109761 on the Development of Human Keloid Fibroblasts. Anal Cell Pathol (Amst). 2021 Feb 10;2021:8883427. doi: 10.1155/2021/8883427. PMID: 33628711; PMCID: PMC7889383. 2. Mao S, Jin J, Li Z, Yang W. Knockdown of long non‑coding RNA ANRIL inhibits the proliferation and promotes the apoptosis of Burkitt lymphoma cells through the TGF‑β1 signaling pathway. Mol Med Rep. 2021 Feb;23(2):146. doi: 10.3892/mmr.2020.11785. Epub 2020 Dec 16. PMID: 33325535; PMCID: PMC7751452. 3. Wang Q, Cai J, Fang C, Yang C, Zhou J, Tan Y, Wang Y, Li Y, Meng X, Zhao K, Yi K, Zhang S, Zhang J, Jiang C, Zhang J, Kang C. Mesenchymal glioblastoma constitutes a major ceRNA signature in the TGF-β pathway. Theranostics. 2018 Sep 9;8(17):4733-4749. doi: 10.7150/thno.26550. PMID: 30279734; PMCID: PMC6160778. 4. He X, Guo X, Zhang H, Kong X, Yang F, Zheng C. Mechanism of action and efficacy of LY2109761, a TGF-β receptor inhibitor, targeting tumor microenvironment in liver cancer after TACE. Oncotarget. 2017 Dec 11;9(1):1130-1142. doi: 10.18632/oncotarget.23193. PMID: 29416682; PMCID: PMC5787425.

In vitro protocol:

In vivo protocol:

1. Wang Q, Cai J, Fang C, Yang C, Zhou J, Tan Y, Wang Y, Li Y, Meng X, Zhao K, Yi K, Zhang S, Zhang J, Jiang C, Zhang J, Kang C. Mesenchymal glioblastoma constitutes a major ceRNA signature in the TGF-β pathway. Theranostics. 2018 Sep 9;8(17):4733-4749. doi: 10.7150/thno.26550. PMID: 30279734; PMCID: PMC6160778. 2. He X, Guo X, Zhang H, Kong X, Yang F, Zheng C. Mechanism of action and efficacy of LY2109761, a TGF-β receptor inhibitor, targeting tumor microenvironment in liver cancer after TACE. Oncotarget. 2017 Dec 11;9(1):1130-1142. doi: 10.18632/oncotarget.23193. PMID: 29416682; PMCID: PMC5787425.

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Inactivation of the TGF-β1/ALK5 axis enhances club cell function and alleviates lung tissue damage to ameliorate COPD progression through the MEK/ERK signaling pathway. Gen Physiol Biophys. 2024 Jan;43(1):37-48. doi: 10.4149/gpb_2023034. PMID: 38312033. 5: Zhang S, Wang Y, Luo D, Cheng Z, Zeng Q, Wang G, Chen M, Zhang S, Luo P. Pirfenidone inhibits TGF-β1-induced metabolic reprogramming during epithelial- mesenchymal transition in non-small cell lung cancer. J Cell Mol Med. 2024 Feb;28(3):e18059. doi: 10.1111/jcmm.18059. Epub 2023 Dec 23. PMID: 38140828; PMCID: PMC10844763. 6: Huang F, Lai J, Qian L, Hong W, Li LC. Differentiation of Uc-MSCs into insulin secreting islet-like clusters by trypsin through TGF-beta signaling pathway. Differentiation. 2024 Jan-Feb;135:100744. doi: 10.1016/j.diff.2023.100744. Epub 2023 Dec 16. PMID: 38128465. 7: Qu P, Shao Z, Zhang Y, He J, Lu D, Wei W, Hua J, Wang W, Wang J, Ding N. Primary cilium participates in radiation-induced bystander effects through TGF-β1 signaling. J Cell Physiol. 2024 Feb;239(2):e31163. doi: 10.1002/jcp.31163. Epub 2023 Nov 27. PMID: 38009273. 8: Lv Y, Huang Y, Fan H, Zhao Y, Ma L, Lan Y, Li C, Chen P, Lou Z, Zhou J. 17β-Estradiol inhibits hydrogen peroxide-induced senescence and apoptosis in human umbilical vein endothelial cells by regulating the THBS1/TGF-β/Smad axis. Mol Cell Endocrinol. 2024 Jan 15;580:112111. doi: 10.1016/j.mce.2023.112111. Epub 2023 Nov 17. PMID: 37979907. 9: Xia Y, Wang H, Shao M, Liu X, Sun F. MAP3K19 Promotes the Progression of Tuberculosis-Induced Pulmonary Fibrosis Through Activation of the TGF-β/Smad2 Signaling Pathway. Mol Biotechnol. 2023 Oct 31. doi: 10.1007/s12033-023-00941-6. Epub ahead of print. PMID: 37906388. 10: Hao Y, Chen P, Guo S, Li M, Jin X, Zhang M, Deng W, Li P, Lei W, Liang A, Qian W. Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-β signaling. Front Med. 2024 Feb;18(1):128-146. doi: 10.1007/s11684-023-1010-1. Epub 2023 Oct 23. PMID: 37870681. 11: Vinod N, Hwang D, Fussell SC, Owens TC, Tofade OC, Copling S, Ramsey JD, Rädler PD, Atkins HM, Livingston EE, Ezzell JA, Sokolsky-Papkov M, Yuan H, Perou CM, Kabanov AV. Combination of Polymeric Micelle Formulation of TGFβ Receptor Inhibitors and Paclitaxel Produce Consistent Response Across Different Mouse Models of TNBC. bioRxiv [Preprint]. 2023 Jun 14:2023.06.14.544381. doi: 10.1101/2023.06.14.544381. PMID: 37398150; PMCID: PMC10312717. 12: Aouimeur I, Sagnial T, Coulomb L, Maurin C, Thomas J, Forestier P, Ninotta S, Perrache C, Forest F, Gain P, Thuret G, He Z. Investigating the Role of TGF-β Signaling Pathways in Human Corneal Endothelial Cell Primary Culture. Cells. 2023 Jun 14;12(12):1624. doi: 10.3390/cells12121624. PMID: 37371094; PMCID: PMC10297110. 13: Ling Y, Li J, Zhou L. Smoking-related epigenetic modifications are associated with the prognosis and chemotherapeutics of patients with bladder cancer. Int J Immunopathol Pharmacol. 2023 Jan-Dec;37:3946320231166774. doi: 10.1177/03946320231166774. PMID: 37011378; PMCID: PMC10074629. 14: Xie B, Zhou H, Liu H, Liao S, Zhou C, Xu D. Salidroside alleviates dexamethasone-induced inhibition of bone formation via transforming growth factor-beta/Smad2/3 signaling pathway. Phytother Res. 2023 May;37(5):1938-1950. doi: 10.1002/ptr.7711. Epub 2022 Dec 25. PMID: 36567454. 15: Xu HN, Jacob A, Li LZ. Optical Redox Imaging Is Responsive to TGFβ Receptor Signalling in Triple-Negative Breast Cancer Cells. Adv Exp Med Biol. 2022;1395:269-274. doi: 10.1007/978-3-031-14190-4_44. PMID: 36527648; PMCID: PMC11289671. 16: Lin P, Tong X, Xue F, Qianru C, Xinyu T, Zhe L, Zhikun B, Shu L. Polystyrene nanoplastics exacerbate lipopolysaccharide-induced myocardial fibrosis and autophagy in mice via ROS/TGF-β1/Smad. Toxicology. 2022 Oct;480:153338. doi: 10.1016/j.tox.2022.153338. Epub 2022 Sep 24. PMID: 36167198. 17: Gu J, Sun Y, Song J, Zhao R, Di X, Zhang Y, Ge X, Zhang S, Gu Y, Sun X. Irradiation induces DJ-1 secretion from esophageal squamous cell carcinoma cells to accelerate metastasis of bystander cells via a TGF-β1 positive feedback loop. J Exp Clin Cancer Res. 2022 Aug 26;41(1):259. doi: 10.1186/s13046-022-02471-6. PMID: 36008860; PMCID: PMC9413943. 18: Geng K, Ma X, Jiang Z, Gu J, Huang W, Wang W, Xu Y, Xu Y. WDR74 facilitates TGF-β/Smad pathway activation to promote M2 macrophage polarization and diabetic foot ulcer wound healing in mice. Cell Biol Toxicol. 2023 Aug;39(4):1577-1591. doi: 10.1007/s10565-022-09748-8. Epub 2022 Aug 19. PMID: 35982296. 19: Li Y, Liu C, Yang L, Li L, Hong L. 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