LY-2109761

Last updated
LY-2109761
LY-2109761 structure.png
Identifiers
  • 4-[2-[4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinolin-7-yl]oxyethyl]morpholine
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
Formula C26H27N5O2
Molar mass 441.535 g·mol−1
3D model (JSmol)
  • C1CC2=C(C(=NN2C1)C3=CC=CC=N3)C4=C5C=CC(=CC5=NC=C4)OCCN6CCOCC6
  • 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
  • Key:IHLVSLOZUHKNMQ-UHFFFAOYSA-N

LY-2109761 is a synthetic compound which acts as a potent and selective inhibitor for the growth factor receptor TGF beta receptor 1. It is used for research into conditions such as pulmonary fibrosis and cancer. [1] [2]

See also

Related Research Articles

<span class="mw-page-title-main">Tyrosine kinase</span> Class hi residues

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.

<span class="mw-page-title-main">Epidermal growth factor receptor</span> Transmembrane protein

The epidermal growth factor receptor is a transmembrane protein that is a receptor for members of the epidermal growth factor family of extracellular protein ligands.

<span class="mw-page-title-main">C-Met</span> Mammalian protein found in Homo sapiens

c-Met, also called tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR), is a protein that in humans is encoded by the MET gene. The protein possesses tyrosine kinase activity. The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor.

<span class="mw-page-title-main">Transforming growth factor beta</span> Cytokine

Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms and many other signaling proteins. TGFB proteins are produced by all white blood cell lineages.

<span class="mw-page-title-main">HER2</span> Mammalian protein found in humans

Receptor tyrosine-protein kinase erbB-2 is a protein that in humans is encoded by the ERBB2 gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently referred to as HER2 or CD340.

<span class="mw-page-title-main">Insulin-like growth factor 1 receptor</span> Cell surface tyrosine kinase associated receptor, quiche mediates the effects of Igf-1

The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 (IGF-1) and by a related hormone called IGF-2. It belongs to the large class of tyrosine kinase receptors. This receptor mediates the effects of IGF-1, which is a polypeptide protein hormone similar in molecular structure to insulin. IGF-1 plays an important role in growth and continues to have anabolic effects in adults – meaning that it can induce hypertrophy of skeletal muscle and other target tissues. Mice lacking the IGF-1 receptor die late in development, and show a dramatic reduction in body mass. This testifies to the strong growth-promoting effect of this receptor.

<span class="mw-page-title-main">Mothers against decapentaplegic homolog 3</span> Protein-coding gene in humans

Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene.

<span class="mw-page-title-main">Mothers against decapentaplegic homolog 7</span> Protein-coding gene in the species Homo sapiens

Mothers against decapentaplegic homolog 7 or SMAD7 is a protein that in humans is encoded by the SMAD7 gene.

Smads comprise a family of structurally similar proteins that are the main signal transducers for receptors of the transforming growth factor beta (TGF-B) superfamily, which are critically important for regulating cell development and growth. The abbreviation refers to the homologies to the Caenorhabditis elegans SMA and MAD family of genes in Drosophila.

The transforming growth factor beta (TGFB) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, cell migration, apoptosis, cellular homeostasis and other cellular functions. The TGFB signaling pathways are conserved. In spite of the wide range of cellular processes that the TGFβ signaling pathway regulates, the process is relatively simple. TGFβ superfamily ligands bind to a type II receptor, which recruits and phosphorylates a type I receptor. The type I receptor then phosphorylates receptor-regulated SMADs (R-SMADs) which can now bind the coSMAD SMAD4. R-SMAD/coSMAD complexes accumulate in the nucleus where they act as transcription factors and participate in the regulation of target gene expression.

<span class="mw-page-title-main">TGF beta 1</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the transforming growth factor beta superfamily of cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation, and apoptosis. In humans, TGF-β1 is encoded by the TGFB1 gene.

<span class="mw-page-title-main">ACVR1B</span>

Activin receptor type-1B is a protein that in humans is encoded by the ACVR1B gene.

<span class="mw-page-title-main">ACVR2A</span> Protein-coding gene in the species Homo sapiens

Activin receptor type-2A is a protein that in humans is encoded by the ACVR2A gene. ACVR2A is an activin type 2 receptor.

The activin type 2 receptors belong to a larger TGF-beta receptor family and modulate signals for transforming growth factor beta ligands. These receptors are involved in a host of physiological processes including, growth, cell differentiation, homeostasis, osteogenesis, apoptosis and many other functions. There are two activin type two receptors: ACVR2A and ACVR2B.

<span class="mw-page-title-main">Endoglin</span> Protein-coding gene in the species Homo sapiens

Endoglin (ENG) is a type I membrane glycoprotein located on cell surfaces and is part of the TGF beta receptor complex. It is also commonly referred to as CD105, END, FLJ41744, HHT1, ORW and ORW1. It has a crucial role in angiogenesis, therefore, making it an important protein for tumor growth, survival and metastasis of cancer cells to other locations in the body.

<span class="mw-page-title-main">Neuropilin</span>

Neuropilin is a protein receptor active in neurons.

<span class="mw-page-title-main">TGF beta receptor 1</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor beta receptor I is a membrane-bound TGF beta receptor protein of the TGF-beta receptor family for the TGF beta superfamily of signaling ligands. TGFBR1 is its human gene.

<span class="mw-page-title-main">ACVRL1</span>

Serine/threonine-protein kinase receptor R3 is an enzyme that in humans is encoded by the ACVRL1 gene.

<span class="mw-page-title-main">Tumor microenvironment</span>

The tumor microenvironment (TME) is the environment around a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix (ECM). The tumor and the surrounding microenvironment are closely related and interact constantly. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.

<span class="mw-page-title-main">GW-788,388</span> Synthetic compound

GW 788388 is a synthetic compound which acts as a potent and selective inhibitor for TGF beta receptor 1. It has applications in research into various disorders such as liver, kidney and heart disease, and potential antiviral properties.

References

  1. Melisi D, Ishiyama S, Sclabas GM, Fleming JB, Xia Q, Tortora G, et al. (April 2008). "LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis". Molecular Cancer Therapeutics. 7 (4): 829–840. doi:10.1158/1535-7163.MCT-07-0337. PMC   3088432 . PMID   18413796.
  2. Tan QY, Cheng ZS (2018). "TGFβ1-Smad Signaling Pathway Participates in Interleukin-33 Induced Epithelial-to-Mesenchymal Transition of A549 Cells". Cellular Physiology and Biochemistry. 50 (2): 757–767. doi: 10.1159/000494241 . PMID   30308508. S2CID   52966340.