Quantifying the relationship between inhibition of VEGF receptor 2, drug-induced blood pressure elevation and hypertension.

ABSTRACT:

Background and purpose

Several anti-angiogenic cancer drugs that inhibit VEGF receptor (VEGFR) signalling for efficacy are associated with a 15-60% incidence of hypertension. Tyrosine kinase inhibitors (TKIs) that have off-target activity at VEGFR-2 may also cause blood pressure elevation as an undesirable side effect. Therefore, the ability to translate VEGFR-2 off-target potency into blood pressure elevation would be useful in development of novel TKIs. Here, we have sought to quantify the relationship between VEGFR-2 inhibition and blood pressure elevation for a range of kinase inhibitors.

Experimental approach

Porcine aortic endothelial cells overexpressing VEGFR-2 (PAE) were used to determine IC₅₀ for VEGFR-2 phosphorylation. These IC₅₀ values were

SUBMITTER: Collins T 

PROVIDER: S-EPMC5786461 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature