Dual Head
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More Great Information on Dual Head:
Which targets to hit for PI3K pathway? selective inhibitors or dual inhibitors?
There is a question:the high selective inhibitors and dual inhibitors,which are better?
When rapamycin is approved in 1999, more and more
PI3K inhibitors
were discoveried by drug development companies. In 2007, temsirolimus,a new drug for PI3K inhibition developed by Pfizer was approved. So many drug companies pay much attention to PI3K inhibitors because they believe that the PI3K pathway is almost invariably on in cancer.
Vanhaesebroeck,the head of the Centre for Cell Signalling at Barts Cancer Institute:
“The big hit came in 2004,with the discovery of the oncogenic mutation of PIK3CA,the gene that encodes the PI3K catalytic subunit p110α.”
This is a simple overview of PI3K-mTOR pathway.
simple overview of PI3K-mTOR pathway
More detail information about PI3k signal pathway, you can go to KEGG to read more about PI3K signal transduction picture and mTOR signal transduction picture.
A article select some recent Phase III and II PI3K pathway inhibitors. So I list some of them on the table.
Name Company Most advanced indications Phase
PI3K inhibitors
BKM120
Novartis Uterine (endometrial) cancer, NSCLC II
GS-1101 Gilead Sciences Chronic lymphocytic leukaemia,
non-Hodgkin’s lymphoma II
PX-886 Oncothyreon Brain cancer II
SAR-245408 Sanofi Uterine (endometrial) cancer, breast cancer II
AKT inhibitors
Perifosine Keryx Biopharmaceuticals Multiple myeloma, colorectal cancer III
MK-2206
Merck & Co. NSCLC, haematological cancer II
VQD-002 VioQuest Pharmaceuticals Solid tumours II
Dual PI3K–mTOR inhibitors
BEZ235
Novartis Uterine (endometrial) cancer II
SAR245409 Sanofi Breast cancer II
There is a question.
Which is better,in high selective PI3K inhibitors and dual PI3K and mTOR inhibitors?
We spent a lot of money and a lot of time to find out better inhibitors.But which is better?
Someone believe that dual PI3K and mTOR inhibitors are better. They think that mTOR is the downstream of PI3K and dual inhibitors of PI3K and mTOR may have better efficacy. Others consider that high select PI3K inhibitors perform better safety than dual inhibitors of PI3K and mTOR.
Reference:
(1) Sanchez, C. G., C. X. Ma, et al. (2011). “Preclinical modeling of combined phosphatidylinositol-3-kinase inhibition with endocrine therapy for estrogen receptor-positive breast cancer.” Breast Cancer Res 13(2): R21.
(2) Holmes, D. (2011). “PI3K pathway inhibitors approach junction.” Nat Rev Drug Discov 10(8): 563-564.