Re: Research at UCI

[Guest guest]

Zavie - thanks.

UCI is here in Orange County- I'll be tracking the

progress.

--- Zavie miller <zmiller@...> wrote:

> Translational Research

> Wen-Hwa Lee, PhD - 2008 (Active) - 6097-08

> Department of Biological Chemistry, University of

> California at Irvine, >

> Irvine, CA US

> Developing IBR Compounds as Rad51 Recombinase

> Inhibitors for Leukemia

> Treatment

>

> Imatinib, a potent inhibitor of Bcr-Abl has been

> successful in treating CML

> patients but faces two major obstacles. One is the

> persistence of

> Bcr-Abl-positive stem cells, which may require

> long-term imatinib therapy.

> The other is relapse of the disease due to the

> emergence of resistance to

> imatinib. It is hypothesized that combining a

> Bcr-Abl tyrosine kinase

> inhibitor with inhibitors of critical downstream

> effectors could

> significantly improve CML treatment. Rad51

> recombinase, an essential

> protein for cell proliferation, is a key downstream

> target of Bcr-Abl

> kinase, which enhances Rad51 expression through

> Stat5 as well as activates

> Rad51 through phosphorylation. We have discovered a

> novel Rad51 inhibitor,

> IBR2 that inhibits Rad51 multimerization and

> activates Rad51 degradation.

> IBR2 synergizes with imatinib in treating K562 cells

> as well as Ba/F3-p210

> cells. Remarkably, this

> compound alone induces apoptosis of Ba/F3 cells with

> imatinib-resistant

> T315I mutant and significantly prolonged the

> lifespan of mice carrying

> Ba/F3-T315I cells.

>

> In this application, we plan to generate more

> effective IBR2 analogues to

> improve the efficacy of treating CML and acute

> myeloid leukemia (AML)

> because 70% of AML have an activated Stat5 that

> enhances Rad51 expression.

> It is anticipated that this newly discovered Rad51

> inhibitor would be

> beneficial in treating these leukemias.

>

>

> Zavie (age 69)

> 67 Shoreham Avenue

> Ottawa, Canada, K2G 3X3

> dxd AUG/99

> INF OCT/99 to FEB/00, CHF

> No meds FEB/00 to JAN/01

> Gleevec since MAR/27/01 (400 mg)

> CCR SEP/01. #102 in Zero Club

> 2.8 log reduction Sep/05

> 3.0 log reduction Jan/06

> 2.9 log reduction Feb/07

> 3.2 log reduction Jun/07

> 3.6 log reduction Sep/07

> e-mail: zmiller@...

> Tel: 613-726-1117

> Fax: 309-296-0807

> Cell: 613-202-0204

> ID: zaviem

>

>

>

> [Non-text portions of this message have been

> removed]

>

>

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