Information about how VX809 works with F508del (He et al. 2012):

What needs to occur with F508del:
The channel needs to be assembled properly, stable at the cell surface and function well at the cell surface.

What occurs with VX809 and F508del:
– VX809 rescued the assembly (folding) at body temperature.
– The VX809 rescued CFTR has a short lifetime (decreased stability) and loses channel activity at body temperature.
– Other medications which stabilise the CFTR could increase the CFTR rescue, these could be combined with VX809 or similar medications that help assembly.

How it interacts:
– Where VX809 acts on the CFTR is unknown, there is only circumstantial evidence that it interacts directly with the protein, possibly during its assembly in the endoplasmic reticulum.
– There are several possible binding sites including the NBD1/CL4 interface. This area has also been targeted by computer models to identify additional correctors.

Source: http://www.fasebj.org/content/early/2012/10/25/fj.12-216119.abstract

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

Category

1. Class 2 Mutations & F508del, 3. Vertex - VX809 & VX661