JAK Inhibitors
ironjustice
Inhibition of JAK therefore will relieve .. increased blood cell
production / glorified bloodletting.
Janus kinase mutations.
Semin Oncol. 2009 Apr;36(2 Suppl 1):S6-11.
Levine RL.
Department of Medicine,
Memorial Sloan-Kettering Cancer Center,
New York, NY 10065, USA. lev...@mskcc.org
The chronic myeloproliferative neoplasms (MPNs)
polycythemia vera (PV), essential thrombocytosis
(ET), and primary myelofibrosis (MF) are commonly
associated with mutations in the Janus kinase gene
JAK2.
A hallmark of PV is an abundance of red blood cells;
ET, too many platelets; and MF, accumulation of
neutrophils and monocytes accompanied by bone
marrow fibrosis and bone marrow failure.
Although knowledge of PV, ET, and MF has expanded
considerably in the last decade, the pathophysiology
behind these disorders is complex, and some of the
underlying mechanisms are still unknown.
The knowledge gap for these diseases has been
compounded by the observation that a subset of patients
with PV, ET, and MF do not present with mutations that
activate JAK2.
Recent studies suggest JAK inhibitors may offer
significant benefit to patients with these MPNs and may
have a role in the treatment of other malignancies that
are also driven, at least in part, by activation of JAK
signaling.
However, additional genetic and functional studies are
needed to identify the patients that will benefit most from
JAK kinase inhibitors.
PMID: 19393837
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http://www.pipelinereview.com/store/product_info.php?products_id=1024
Janus Kinase (JAK) Inhibitors
Product description
The present Competitive Intelligence Report about new developments
in the pipeline of inhibitors of the janus-associated kinase (JAK)
provides
a competitor evaluation in the field of R&D projects from preclinical
stages up to advanced clinical phases of JAK Inhibitors as of December
2008.
As cytokines play pivotal roles in immunity and inflammation,
targeting of
cytokines and their receptors represents an effective means of
treating such
diseases.
Janus kinases (JAK) are a small family of receptor-associated
kinases,
that together with signal transducers and activators of transcription
(STAT),
provide a rapid signalling pathway for cytokines.
Four JAKs have been identified: JAK1, JAK2, JAK3 and tyrosine kinase
2 (Tyk2). JAK3 has attracted much attention as an anti-inflammatory
drug
target because of its restricted hematopoietic tissue expression and
because
of its specific association with the common gamma chain of the
interleukin-2
(IL-2) receptor which is shared by the receptors for IL-4, IL-7, IL-9,
IL-15 and
IL-21.
Quite a number of companies are developing selective JAK3 inhibitors
as
JAK3 appears not to have functions outside of hematopoetic cells.
Pfizer leads the field with evaluation of JAK3 inhibition in a number
of
inflammatory diseases including rheumatoid arthritis, asthma,
ulcerative
colitis, Crohn’s disease, psoriasis and prevention of transplant
rejection.
Results from the first phase II study of Pfizer’s JAK3 inhibitor
revealed the
best reported results so far for a small molecule tested in rheumatoid
arthritis.
JAK2 gain-of-function mutations (JAK2V617F) underlie a subset of
disorders
collectively referred to as myeloproliferative disorders.
The most advanced JAK2 inhibitors are also being evaluated in phase II
trials
for myelofibrosis, polycythemia vera and essential thrombocythemia.
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk