220904-83-6 Usage
Description
GW5074, also known as GW-5074, is a potent inhibitor of cRAF1 kinase with an IC50 value of 9 nM. It exhibits a high degree of selectivity for cRAF1 over other kinases such as CDK1, CDK2, c-src, ERK2, MEK, p38, Tie2, VEGFR2, and c-fm. GW5074 is characterized by its cell permeability and has been shown to have neuroprotective effects in vivo through a mechanism that is independent of MEK, ERK, and Akt signaling pathways.
Uses
Used in Pharmaceutical Industry:
GW5074 is used as a specific inhibitor of cRaf1 for various applications, including its role in C2 murine skeletal myoblasts, HT-29 colorectal adenocarcinoma cell line, and neutrophils. Its high selectivity for cRAF1 makes it a valuable tool in the development of targeted therapies for various diseases and conditions.
Used in Cancer Research:
In the field of cancer research, GW5074 is used as a potent inhibitor of cRAF1 kinase, which plays a crucial role in the regulation of cell proliferation and survival. By inhibiting cRAF1, GW5074 can potentially disrupt the signaling pathways that promote cancer cell growth and contribute to the development and progression of tumors.
Used in Neuroprotective Studies:
GW5074 is also used in neuroprotective studies due to its demonstrated neuroprotective effects in vivo. Its ability to provide neuroprotection through a mechanism independent of MEK, ERK, and Akt signaling pathways makes it a valuable compound for investigating the potential therapeutic applications in neurodegenerative diseases and conditions.
Used in Cell Signaling Research:
In cell signaling research, GW5074 is employed as a tool to study the role of cRAF1 kinase in various cellular processes. Its high selectivity for cRAF1 over other kinases allows researchers to specifically investigate the effects of cRAF1 inhibition on cellular signaling pathways and the potential implications for disease development and treatment.
Biological Activity
Potent, selective and cell-permeable c-Raf1 kinase inhibitor (IC 50 = 9 nM). Displays ≥ 100-fold selectivity for raf kinase over CDK1, CDK2, c-src, ERK2, MEK, p38, Tie2, VEGFR2 and c-fm.
Biochem/physiol Actions
GW5074 is a cRaf1 kinase inhibitor, which is placed immediately downstream of Ras in the Motogen activated protein kinase (MAPK) signaling pathway. It elicits protection in GW5074 prevents degeneration in Huntington′s disease and also have therapeutic potential in treating neurodegenerative disorders. GW5074 in combination with anti-inflammatory drug, dexamethasone, attenuates sidestream smoke-induced airway inflammation.
References
1) Chang et al. (2005), Phorbol 12-myristate 13-acetate upregulates cyclooxygenase-2 expression in human pulmonary epithelial cells via Ras, Raf-1, ERK, and NF-kappaB, but not p38 MAPK pathways; Cell Signal., 217 299
2) Huang et al. (2006), Fibroblast growth factor-2 suppresses oridonin-induced L929 apoptosis through extracellular signal-regulated kinase-dependent and phosphatidylinositol 3-kinase-independent pathway; J. Pharmacol. Sci., 102 305
3) Lackey et al. (2000), The discovery of potent cRaf1 kinase inhibitors; Bioorg. Med. Chem. Lett., 10 223
4) Chen et al. (2004), Bradykinin B2 receptor mediates NF-kappaB activation and cyclooxygenase-2 expression via the Ras/Raf-1/ERK pathway in human airway epithelial cells; J. Immunol., 173 5219
Check Digit Verification of cas no
The CAS Registry Mumber 220904-83-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,2,0,9,0 and 4 respectively; the second part has 2 digits, 8 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 220904-83:
(8*2)+(7*2)+(6*0)+(5*9)+(4*0)+(3*4)+(2*8)+(1*3)=106
106 % 10 = 6
So 220904-83-6 is a valid CAS Registry Number.
InChI:InChI=1/C15H8Br2INO2/c16-11-4-7(5-12(17)14(11)20)3-10-9-6-8(18)1-2-13(9)19-15(10)21/h1-6,20H,(H,19,21)/b10-3-
220904-83-6Relevant articles and documents
Hydroxybenzylidene-indolinones, c-di-AMP synthase inhibitors, have antibacterial and anti-biofilm activities and also re-sensitize resistant bacteria to methicillin and vancomycin
Opoku-Temeng, Clement,Dayal, Neetu,Miller, Jacob,Sintim, Herman O.
, p. 8288 - 8294 (2017)
c-di-AMP signaling regulates a myriad of physiological processes in Gram-positive bacteria and mycobacteria. c-di-AMP synthase (DAC) is essential in many human pathogens including Staphylococcus aureus, Listeria monocytogenes and Streptococcus pneumoniae and could become an important antibacterial drug target. In our continuing efforts to identify diverse DAC inhibitors, we uncovered hydroxybenzylidene-indolinones as new DAC inhibitors. Interestingly, these compounds also possess antibacterial activities and inhibit biofilm formation. Importantly, methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis could be re-sensitized to methicillin and vancomycin, respectively, by hydroxybenzylidene-indolinones.
The discovery of potent cRaf1 kinase inhibitors
Lackey, Karen,Cory, Michael,Davis, Ronda,Frye, Stephen V.,Harris, Philip A.,Hunter, Robert N.,Jung, David K.,McDonald, O. Bradley,McNutt, Robert W.,Peel, Michael R.,Rutkowske, Randy D.,Veal, James M.,Wood, Edgar R.
, p. 223 - 226 (2007/10/03)
A series of benzylidene-1H-indol-2-one (oxindole) derivatives was synthesized and evaluated as cRaf-1 kinase inhibitors. The key features of the molecules were the donor/acceptor motif common to kinase inhibitors and a critical acidic phenol flanked by two substitutions. Diverse 5-position substitutions provided compounds with low nanomolar kinase enzyme inhibition and inhibited the intracellular MAPK pathway. (C) 2000 Elsevier Science Ltd. All rights reserved.
