SX70393 may be tried in 2008

[Guest guest]

This article was last updated December, 2007 and supposedly this new drug,

SX70393 is effective against the gatekeeper of resistance. Perhaps this is the

drug we turtles are waiting on. I hope you will find this as interesting as I

did - I'm one of those really old turtles.

NEW YORK (Reuters Health) - A new Abl kinase inhibitor that eliminates

resistance to nilotinib and dasatinib in the treatment of chronic myeloid

leukemia (CML) in mice and in human cell lines was described this week at the

49th annual meeting of the American Society of Hematology in Atlanta, Georgia.

" There is only a small recovery after the development of resistance in CML, "

principal investigator Dr. Deininger of Oregon Health and Science

University Cancer Institute in Portland told Reuters Health. The new drug, with

the investigational name SGX70393 (SGX Pharmaceuticals), " is effective against

the gatekeeper of resistance, " he explained.

SGX70393 is an azapyridine-based Abl kinase inhibitor. Bcr-Abl-3151, a mutation

that prevents drug binding, is present in most patients with CML who relapse

after treatment with the Bcr-Abl kinase inhibitors dasatinib or nilotinib.

SGX70393 is effective against Bcr-Abl and Bcr-Abl-3151. " Remarkably, " Dr.

Deininger's group reported, " outgrowth of resistant clones is completely

suppressed " in tumor cell lines treated with SGX70393 in combination with

nilotinib or dasatinib. SGX70393 inhibited tumor growth driven by Bcr-Abl-1351

in mice, while imatinib had no effect.

" Dr. Deininger commented that, " when combined with the tyrosine kinase

inhibitors, this drug can induce longer-lasting remissions and it could be used

to treat patients with more aggressive strains of CML. It could also be used

earlier in the course of treatment to prevent resistance from developing in the

first place. " SGX Pharmaceuticals plans to file an NDA in the second half of

2008.

Chief Scientific Officer of SGX Pharmaceuticals says, " Moreover, the results

obtained with our collaborators at the Oregon Health & Science University Cancer

Institute demonstrate the potential of targeted combination therapy for CML. A

number of influential thought leaders believe that effective management of

newly-diagnosed CML will depend on long-term treatment with multiple agents

possessing non-overlapping resistance profiles. "

According to SGX officials, " SGX393 has shown both potent in vitro blockade

of the activity of BCR-ABL and in vivo activity against human leukemic cells

that depend on BCR-ABL for their uncontrolled growth and proliferation. In

addition, SGX393 has shown potent activity against a broad spectrum of mutant

forms of BCR-ABL that render this cancer target resistant to imatinib (Gleevec

®), the current standard of care for CML. One of the key drug resistant forms

of BCR-ABL inhibited by SGX393 is the T315I mutation, which is also resistant to

the two second-generation BCR-ABL inhibitors, nilotinib (Tasigna ®) and

dasatinib (Sprycel ®). In addition, SGX is engaged in a strategic

collaboration with Novartis that aims to discover and develop next generation

BCR-ABL inhibitors for treatment of newly-diagnosed CML patients. "

AMEN to that, it remains to be seen if it can be the gatekeeper of resistance as

implied. Eli Lily was supposed to buy SGX in July, 2008.

http://www.sgxpharma.com/

Blessings,

Lottie