A purine scaffold HSP90 inhibitor BIIB021 has selective activity against KSHV-associated primary effusion lymphoma and blocks vFLIP K13-induced NF-κB.

ABSTRACT:

Purpose

Kaposi sarcoma-associated herpes virus (KSHV)-associated primary effusion lymphomas (PEL) have extremely poor prognosis when treated with conventional chemotherapy. KSHV-encoded viral FLICE-inhibitory protein (vFLIP) K13 binds to the IkappaB kinase (IKK) complex to constitutively activate the NF-κB pathway, which has been shown to be essential for the survival and proliferation of PEL cells. The molecular chaperone HSP90 is a component of the IKK complex and is required for its activity.

Experimental design

We have analyzed the effect of HSP90 inhibitors on the survival and proliferation of PEL cells and on the activity of the NF-κB pathway.

Results

We show that BIIB021, a purine scaffold-based orally administrable HSP90 inhibitor, shows preferential cytotoxic

SUBMITTER: Gopalakrishnan R 

PROVIDER: S-EPMC3804723 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature