NVP-BAW2881

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.

Uses

6-[(2-amino-4-pyrimidinyl)oxy]-N-[3-(trifluoromethyl)phenyl]-1-naphthalenecarboxamide is a selective vascular endothelial growth factor (VEGF) receptor inhibitor. VEGF receptors play important roles in angiogenesis and vascular permeability.

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.