BAW2881 (NVP-BAW2881) is a novel vascular endothelial growth factor (VEGF) receptor tyrosine-kinase inhibitor that potently inhibits VEGFR1-3 at 1.0-4.3 nanomolar (nM) concentrations and inhibits PDGFRβ, c-Kit, and RET at 45-72 nM concentrations. NVP-BAW2881 inhibited proliferation, migration, and tube formation of human umbilical vein endothelial cells and lymphatic endothelial cells.
In vivo: BAW2881 targets the tyrosine kinase domain of murine, porcine, and human VEGFR2. It can be administered both orally and topically, but has not been tested in humans. Studies in VEGF-A transgenic mice showed that oral and topical administration of NVP-BAW2881 strongly reduced psoriasis-like inflammation in ear skin. In comparison to control mice, treated mice showed significant improvement in ear swelling, skin inflammation, lymph node enlargement, and skin erythema. Though both modes of administration were effective, systemic administration of NVP-BAW2881 was more potent than topical administration.
|Cell lines||Human dermal lymphatic endothelial cells(LECs), human umbilical vein endothelial cells(HUVECs)|
|Preparation method||HUVECs or LECs (1.2×103) were seeded into fibronectin-coated 96-well plates. After 24 hours, the cells were transferred into LEC medium containing 2% fetal bovine serum and incubated for an additional 24 hours. Cells(eight wells/condition) were incubated with medium alone(control), 20 ng/ml VEGF-A, or a combination of 20 ng/ml VEGF-A and 1 nmol/L to 1 mol/L NVP-BAW2881. Proliferation was also assayed in LECs incubated with 500 ng/ml VEGF-C. The dimethyl sulfoxide concentration was adjusted to 0.1% in all wells. After 72 hours, cells were incubated with 5-methylumbelliferylheptanoate for subsequent fluorescent quantification of viable cells, using a SpectraMax Gemini electron microscope.|
|Concentrations||1 nmol/L to 1 mol/L|
|Incubation time||72 h|
|Animal models||K14/VEGF-A TG mice|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO: ≥ 60 mg/mL
Ethanol 20 mg/mL
A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis.
Bold G, et al. J Med Chem. 2016 Jan 14;59(1):132-46. PMID: 26629594.
Vascular endothelial growth factor inhibitors: investigational therapies for the treatment of psoriasis.
Weidemann AK, et al. Clin Cosmet Investig Dermatol. 2013 Sep 26;6:233-44. PMID: 24101875.
Inhibition of chronic and acute skin inflammation by treatment with a vascular endothelial growth factor receptor tyrosine kinase inhibitor.
Halin C, et al. Am J Pathol. 2008 Jul;173(1):265-77. PMID: 18535184.
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