861875-60-7 Usage
Description
BAW 2881 is a vascular endothelial growth factor receptor (VEGFR) inhibitor (IC50s = 0.82, 0.037, and 0.42 μM for hVEGFR1, 2, and 3, respectively). It inhibits Tie2 and RET with IC50 values of 0.65 and 0.41 μM, respectively, but demonstrates IC50 values great than 10 μM toward a large panel of additional kinases. BAW 2881 was shown to block VEGF-A-induced proliferation, migration, and tube formation of human umbilical vein endothelial cells and lymphatic endothelial cells in vitro. In a mouse model of psoriasis, both oral and topical administration of BAW 2881 reduced psoriasis-like inflammation in ear skin. Topical application of BAW 2881 also reduced VEGF-A-induced vascular permeability and inhibited contact hypersensitivity reactions and UV-B-induced erythema in the skin of domestic pigs.
in vitro
previous study showed that baw2881 could inhibit a limited number of kinases including c-raf, b-raf, ret, abl, and tie-2 at submicromole ic50s. baw2881 could also inhibit the ligand induced autophosphorylation of ret, pdgfr, and kit kinases. moreover, low ic50 value (0.12 ± 0.06 nm) demonstrated that baw2881 remarkably abrogated vegf induced proliferation [1].
in vivo
in a psoriasis mouse model, baw2881 was able to reduce the number of blood and lymphatic vessels and infiltrating leukocytes in the skin, and normalize the epidermal architecture. baw2881 also showed strong anti-inflammatory effects in acute inflammation models. moreover, the pretreatment with topical baw2881 could significantly inhibit vegf-a-induced vascular permeability in the skin of both pigs and mice. in addition, it was found that the topical application of baw2881 was able to reduce the inflammatory response in pig skin caused by uv-b irradiation or by contact hypersensitivity reactions [2].
IC 50
1.0-4.3 nm for vegfr1-3
references
[1] bold g et al. a novel potent oral series of vegfr2 inhibitors abrogate tumor growth by inhibiting angiogenesis. j med chem. 2016 jan 14;59(1):132-46. [2] halin c,fahrngruber h,meingassner jg,bold g,littlewood-evans a,stuetz a,detmar m. inhibition of chronic and acute skin inflammation by treatment with a vascular endothelial growth factor receptor tyrosine kinase inhibitor. am j pathol.2008 jul;173(1):265-77.
Check Digit Verification of cas no
The CAS Registry Mumber 861875-60-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,6,1,8,7 and 5 respectively; the second part has 2 digits, 6 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 861875-60:
(8*8)+(7*6)+(6*1)+(5*8)+(4*7)+(3*5)+(2*6)+(1*0)=207
207 % 10 = 7
So 861875-60-7 is a valid CAS Registry Number.
861875-60-7Relevant articles and documents
A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis
Bold, Guido,Schnell, Christian,Furet, Pascal,McSheehy, Paul,Brüggen, Josef,Mestan, Jürgen,Manley, Paul W.,Drückes, Peter,Burglin, Marion,Dürler, Ursula,Loretan, Jacqueline,Reuter, Robert,Wartmann, Markus,Theuer, Andreas,Bauer-Probst, Beatrice,Martiny-Baron, Georg,Allegrini, Peter,Goepfert, Arnaud,Wood, Jeanette,Littlewood-Evans, Amanda
, p. 132 - 146 (2016/01/28)
This paper describes the identification of 6-(pyrimidin-4-yloxy)-naphthalene-1-carboxamides as a new class of potent and selective human vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitors. In biochemical and cellular assays, the compounds exhibit single-digit nanomolar potency toward VEGFR2. Compounds of this series show good exposure in rodents when dosed orally. They potently inhibit VEGF-driven angiogenesis in a chamber model and rodent tumor models at daily doses of less than 3 mg/kg by targeting the tumor vasculature as demonstrated by ELISA for TIE-2 in lysates or by immunohistochemical analysis. This novel series of compounds shows a potential for the treatment of solid tumors and other diseases where angiogenesis plays an important role.
BICYCLIC AMIDES AS KINASE INHIBITORS
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Page/Page column 42, (2010/11/08)
The invention relates to compounds of formula (I) and their use in the treatment of the animal or human body, to pharmaceutical compositions comprising a compound of formula I and to the use of a compound of formula I for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as in particular tumour diseases.
