Grant: Operating Grant
University of British Columbia
$390,802.00
Small molecule SHIP agonists for inhibiting the phosphoinositide 3-kinase pathway
FY 2009-10
Summary
The growth and survival of cells requires the action of an intricate network of pathways and mechanisms inside the cell. The PI3K pathway is one key component and anti-cancer drugs are being developed which block this pathway in order to kill cancer cells. However, a novel and powerful approach for inhibiting the PI3K pathway involves activating the natural brakes of this system. This brake is the protein SHIP which serves normally to limit cell growth and action.We developed a way to turn SHIP using a small molecule we isolated by screening a library of marine natural products for activators of SHIP. This molecule, pelorol and subsequent structurally related derivatives AQX-016A and AQX-MN100 are not only
able to activate SHIP in an enzyme assay in vitro, but as predicted is also able to inhibit multiple myeloma tumour cell growth. However, the known role of SHIP in regulating blood cell function suggest that SHIP activators could have additional beneficial actions on the multiple myeloma disease process. Studies are now proposed to examine these possibilities.
Department
Program
Operating Grant
Recipient
Location
British Columbia, Canada
Recipient Type
Academia
Type
Grant
Source
CIHR Funding Decisions Database
As published
Id
201656
Name
Mui Alice L
Region
British Columbia
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Cancer Research
Theme2
Biomedical
Prcname2
Cancer Progression & Therapeutics 2
Projecttitle
Small molecule SHIP agonists for inhibiting the phosphoinositide 3-kinase pathway
Programtype2
Operating Grants
Orgnameinp2
University of British Columbia
Cihramount2
$390,802
Cihrequipment2
$0
Programname2
Operating Grant
Keyworddelim
Biomarkers Of Disease; Hemopoietic Cancer; Phosphoinositide 3-Kinase Pathway; Signal Transduction; Targetted Therapeutics
Abstract
The growth and survival of cells requires the action of an intricate network of pathways and mechanisms inside the cell. The PI3K pathway is one key component and anti-cancer drugs are being developed which block this pathway in order to kill cancer cells. However, a novel and powerful approach for inhibiting the PI3K pathway involves activating the natural brakes of this system. This brake is the protein SHIP which serves normally to limit cell growth and action.We developed a way to turn SHIP using a small molecule we isolated by screening a library of marine natural products for activators of SHIP. This molecule, pelorol and subsequent structurally related derivatives AQX-016A and AQX-MN100 are not only
able to activate SHIP in an enzyme assay in vitro, but as predicted is also able to inhibit multiple myeloma tumour cell growth. However, the known role of SHIP in regulating blood cell function suggest that SHIP activators could have additional beneficial actions on the multiple myeloma disease process. Studies are now proposed to examine these possibilities.
Competitiondate
201003
Approvedterm2
3 yrs 0 mth
Pinamesdelim
Mui, Alice L
Approvedterm
3 ans 0 mois
Cihrcontribution2
~ $390,802~ $0~
