Friday, May 13, 2011

Hsp-90 revisited

It is always nice to see one’s old research fellows doing well. A couple of years ago Giles Best was working in our lab on CLL and I see he is now in Australia, working with Stephen Mulligan in Sydney. He has just published a paper in the British Journal of Haematology on a novel Hsp-90 inhibitor, SNX7081.

Readers will remember that there was a lot of excitement about the Hsp90 inhibitor, 17-AAG, particularly since the up-regulation of ZAP-70 used Hsp-90 as a chaperon. Recently there are suggestions that Hsp-90 inhibitors have promise in targeting cells with mutations of ATM and TP53. However, because of its quinine moiety at its core, 17-AAG looks like proving too toxic for clinical use.

Consequently, novel synthetic inhibitors have been developed including a family of products by Serenex. One of these is studied here. They have looked at the activity of an inhibitor, SNX7801, against a panel of eight haematological cell lines and 23 CLL patient samples. They found that SNX7081 is significantly more potent than 17-AAG in reducing the number of viable tumour cells by causing dramatic cell-cycle arrest without necessitating the TP53 pathway to be intact and by significantly reducing the amount of ZAP-70 expressed.

SNX7081 is recommended for clinical trials

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