| p38 alpha has
been widely validated as a target
for inflammatory disease including
rheumatoid arthritis, asthma,
COPD and psoriasis. The gene
plays a critical role in the
production of certain cytokines
by modulating response to environmental
stress and inflammatory cytokines,
by phosphorylating key downstream
proteins. p38 alpha has also
been implicated in cancer, CNS,
and diabetes. |
|
| Xcovery's p38
therapy is a small molecule which
will reduce or stop the production
of TNF-alpha, and IL-1. These
compounds licensed from Scripps
potentially address the $13B
annual market for branded anti-inflammatory
therapies and/or the unmet need
for effective topical psoriasis
treatment. Xcovery's lead p38
compound is expected to enter
clinical development in early
2008. |
|
Objective
|
To
discover p38a selective
inhibitors with good potency
and drug properties. |
Background
|
Most
of the current p38 inhibitors
do not have the proper
balance of all three key
properties: selectivity,
potency, drug properties
(PK, solubility, etc.).
In particular, lack of
selectivity remains the
most important issue for
many of the current p38
compounds in clinical trials. |
Hypothesis
|
Analyzed
all 494 typical protein
kinases using structural
bioinformatic techniques,
identified a unique binding
mode by which highly selective
p38 inhibitors might be
designed. |
Status
(April 2007)
|
| » |
Low
nM potency against
p38a in
in vitro assays |
| » |
>10
fold selectivity
against p38b |
|
| Next Milestone |
In vivo
efficacy by early summer,
2007 |
|
| |
|