VT-346 (TNF-α BINDING PROTEIN)
VT-346

 

VT-346 is a 43 kDa secreted glycoprotein that is a novel and potent inhibitor of human TNF-α.  In pre-clinical testing, the compound has demonstrated an extremely high affinity for human TNF-α, in the order of 10-25 times that of some currently marketed anti-TNF therapies.  The gene was isolated, cloned into a baculovirus expression system, and small amounts of the recombinant protein were purified and examined for binding activities using Biacore analysis.  It was confirmed that the viral TNF-binding protein (TNF-bp) was able to bind human TNF-α with very high affinity (Table 1).

 

                               Affinity to human TNF-α

Product

                         Kd

Vaccinia CrmC

              6530 pM

Enbrel (etanercept)

              1150 pM

Cowpox CrmB                 

                700 pM

Remicade (infliximab)     

                450 pM

Cowpox CrmC

                223 pM

Mouse TNF- α receptor

                200 pM

VT-346 (TNF-α bp)

                  43 pM

 

Table 1:  Dissociation constants of TNF-α binding proteins
     demonstrate potent binding to human TNF.

 

Preliminary in vivo data in a model of vascular inflammation also demonstrates potent drug effects at extremely low doses.