once or twice daily oral irreversible egfr AND her2 inhibitor being developed inChina
 

appears more efficacious than lapatinib (very early studies on cell cultures, mice)--open access article

PLoS One. 2011;6(7):e21487. Epub 2011 Jul 18.
AST1306, A Novel Irreversible Inhibitor of the Epidermal Growth Factor Receptor 1 and 2, Exhibits Antitumor Activity Both In Vitro and In Vivo.
Xie H, Lin L, Tong L, Jiang Y, Zheng M, Chen Z, Jiang X, Zhang X, Ren X, Qu W, Yang Y, Wan H, Chen Y, Zuo J, Jiang H, Geng M, Ding J.
Source
State Key Laboratory of Drug Research, Division of Antitumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Abstract
Despite the initial response to the reversible, ATP-competitive quinazoline inhibitors that target ErbB-family, such a subset of cancer patients almost invariably develop resistance. Recent studies have provided compelling evidence that irreversible ErbB inhibitors have the potential to override this resistance. Here, we found that AST1306, a novel anilino-quinazoline compound, inhibited the enzymatic activities of wild-type epidermal growth factor receptor (EGFR) and ErbB2 as well as EGFR resistant mutant in both cell-free and cell-based systems. Importantly, AST1306 functions as an irreversible inhibitor, most likely through covalent interaction with Cys797 and Cys805 in the catalytic domains of EGFR and ErbB2, respectively. Further studies showed that AST1306 inactivated pathways downstream of these receptors and thereby inhibited the proliferation of a panel of cancer cell lines. Although the activities of EGFR and ErbB2 were similarly sensitive to AST1306, ErbB2-overexpressing cell lines consistently exhibited more sensitivity to AST1306 antiproliferative effects. Consistent with this, knockdown of ErbB2, but not EGFR, decreased the sensitivity of SK-OV-3 cells to AST1306. In vivo, AST1306 potently suppressed tumor growth in ErbB2-overexpressing adenocarcinoma xenograft and FVB-2/N(neu) transgenic breast cancer mouse models, but weakly inhibited the growth of EGFR-overexpressing tumor xenografts. Tumor growth inhibition induced by a single dose of AST1306 in the SK-OV-3 xenograft model was accompanied by a rapid (within 2 h) and sustained (≥24 h) inhibition of both EGFR and ErbB2, consistent with an irreversible inhibition mechanism. Taken together, these results establish AST1306 as a selective, irreversible ErbB2 and EGFR inhibitor whose growth-inhibitory effects are more potent in ErbB2-overexpressing cells.

PMID: 21789172

Re: once or twice daily oral irreversible egfr AND her2 inhibitor being developed inC
 

Lani- how long does it usually take from this stage to trials in humans?

Thanks
Ellie

Re: once or twice daily oral irreversible egfr AND her2 inhibitor being developed inC
 

Elly it is in Phase 1 in China already. Yes I love the fact that little regulation allow for fast progress in that country. If only things were carried out with the type of professionalism we can find in the west (which hopefully they will improve on and learn not to cut corners as much) we will all go there pretty soon as oppose to be on the most toxic drug possible licensed 25 to 50 years ago on the basis that there are too many risk trialling these apparently much less toxic products..

From their paper: "Our data establish AST1306, which is currently in phase I clinical trial in China, as a novel irreversible ErbB inhibitor that deserves further development."

I share my views with the father of the DNA discovery:
James Watson: 'cancer research is over regulated'
http://www.guardian.co.uk/science/20...ancer-research

Re: once or twice daily oral irreversible egfr AND her2 inhibitor being developed inC
 

Thanks FOB for cheering me up! Glad to hear it's already happening as sometimes some really promising research seems never to go anywhere!

Wouldn't it be brilliant if some already identified and used substance could actually be our cure.

Ellie

Re: once or twice daily oral irreversible egfr AND her2 inhibitor being developed inC
 

Yes Elly many promising research never go anywhere including the elctric car (which was put in service 20 years ago then withdrawn, not for fault but indeed lack of..), sun energy improvement and water splitting ( i.e car running on water)..but we have complete dedicated global warming governement agencies and charities ect.. despite cars being one of the most polluting things..

Now in Europe a new directive (May 11) is making the use of medicinal herb the priviledge of the few (i.e. again putting entry barriers, affordable by the few, like it does for trial costs & regulations) with the new directive charging up an upfront "registration fee" fee up to 120, 000 Euro if one wants to sell a plant extract (and yes per extract).. Things are not improving but getting worse..I used to be pro Europe but realised that we are now governed by people we have not elected themselves serving the interest of.. judging by the directive big business.

Although for her2 and a few specific one I do hope that they find at least a drug we will have to take forever but give us a full life time.. i'd be happy with that.

yes I am in a ranting mood..:-)

Re: once or twice daily oral irreversible egfr AND her2 inhibitor being developed inC
 

It would be interesting to learn if there are any cardiac issues.

Re: once or twice daily oral irreversible egfr AND her2 inhibitor being developed inC
 

FOB,
Some of that anti-supplement sentiment is trying to get traction here too..all while systems (private & socialized) bemoan the cost of pharma.