948557-43-5 Usage
Description
Tie2 kinase inhibitor, also known as Tunica interna endothelial cell kinase 2 (Tie2) inhibitor, is a selective and reversible inhibitor of Tie2 kinase activity. It is an endothelium-specific receptor tyrosine kinase that plays a crucial role in the development of embryonic vasculature and in angiogenesis and vascular maintenance in adult tissues. With an IC50 value of 250 nM, Tie2 kinase inhibitor is 200-fold more potent for inhibition of Tie2 compared to p38.
Uses
Used in Pharmaceutical Industry:
Tie2 kinase inhibitor is used as a research tool for studying the role of Tie2 kinase in various biological processes, including angiogenesis and vascular maintenance. It helps researchers understand the underlying mechanisms of these processes and develop potential therapeutic strategies for related diseases.
Used in Cancer Research:
Tie2 kinase inhibitor is used as an anti-angiogenic agent for studying and treating cancer. It has been shown to reduce angiogenesis in a Matrigel neovascularization assay and to delay tumor growth in MOPC-315 plasmacytoma and SVR angiosarcoma xenograft models. By inhibiting Tie2 kinase activity, it can potentially disrupt the formation of new blood vessels that supply nutrients and oxygen to tumors, thereby limiting their growth and progression.
Used in Drug Development:
Tie2 kinase inhibitor is used as a lead compound in the development of new drugs targeting Tie2 kinase for the treatment of various diseases, including cancer, age-related macular degeneration, and diabetic retinopathy. Its high potency and selectivity make it a promising candidate for further optimization and development into a therapeutic agent.
Biological Activity
genetic studies have identified the crucial roles of tie receptors (tie1 & tie2) in the development and function of endothelial tissues, including promoting the survival, maturation and functional integrity of the vasculature. tie2 kinase inhibitor is suggested to block vascular construction via suppressing tie2, and in this way it is expected to disrupt tumor growth and angiogenesis. [1]
in vitro
tie2 kinase inhibitor exhibited significant inhibitory effect on tie2 auto-phosphorylation and disrupted its downstream signal transduction in a dose dependent manner in human aortic endothelial cells. in addition, tie2 kinase inhibitor exhibits moderately suppressed the activity of tie2 tyrosine kinase in hel cells with ic50 of 232 nm. [2, 3]
in vivo
matrigel mouse model of angiogenesis was adopted for in vivo study. tie2 kinase inhibitor at doses of 25 and 50 mg/kg (i.p., b.i.d) reduced 41% and 70% of angiogenesis, respectively. in a mopc-315 plasmacytoma xenograft model, tie2 kinase inhibitor modestly suppressed tumor growth in nude mice in a dose-dependent manner. [4]
IC 50
a reversible and selective inhibitor of tie2 with ic50 of 0.25 m, whose selectivity is 200-fold higher than that of p38.
references
[1] lagreca s, arcari j, baker d, borzillo g, chen j, clark t, cohen b, hungerford w, kakar s, kanter a, knauth k, lu y, martinez-alsina l, marx m, patel n, soderstrom c, tkalcevic g, thompson c, troutman m, vincent p, wessel m. identification of selective, orally active tie2 kinase inhibitors and discovery of ce-245,677 and pf-371,989. cancer res. 2007 may; 67: 3259.[2] liu l , lina t, coleb a, wenc r, zhao l, bresciab mr, jacoba b, hussainb z, appella k, hendersonb i, webba m. dentification and characterization of small-molecule inhibitors of tie2 kinase. febs lett. 2008 mar; 582(5): 785-91.[3] semones m, feng y, johnson n, adams jl, winkler j, hansbury m. pyridinylimidazole inhibitors of tie2 kinase. bioorg med chem lett. 2007 sep; 17(17): 4756-60. [4]hasenstein jr, kasmerchak k, buehler d, hafez gr, claery k, moody js, kozak kr. efficacy of tie2 receptor antagonism in angiosarcoma. neoplasia 2012 feb;14(2):131-40.[5] garcia-manero g, khoury hj, jabbour e, lancet j, winski sl, cable l, rush s, maloney l, hogeland g, ptaszynski m, calvo mc, bohannan z, kantarjian h, komrokji r. a phase i study of oral arry-614, a p38 mapk/tie2 dual inhibitor, in patients with low or intermediate-1 risk myelodysplastic syndromes. clin cancer res. 2015 mar 1;21(5):985-94.
Check Digit Verification of cas no
The CAS Registry Mumber 948557-43-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,4,8,5,5 and 7 respectively; the second part has 2 digits, 4 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 948557-43:
(8*9)+(7*4)+(6*8)+(5*5)+(4*5)+(3*7)+(2*4)+(1*3)=225
225 % 10 = 5
So 948557-43-5 is a valid CAS Registry Number.
948557-43-5Relevant articles and documents
Pyridinylimidazole inhibitors of Tie2 kinase
Semones, Marcus,Feng, Yanhong,Johnson, Neil,Adams, Jerry L.,Winkler, Jim,Hansbury, Michael
, p. 4756 - 4760 (2008/12/21)
This communication details the evolution of the screening lead SB-203580, a known CSBP/p38 kinase inhibitor, into a potent and selective Tie2 tyrosine kinase inhibitor. The optimized compound 5 showed efficacy in an in vivo model of angiogenesis and a MOP
