Table 2

TABLE of compounds targeting the PI3K pathway currently in clinical trials. List of PI3K pathway inhibitors currently in clinical trials or approved for treating inflammatory disease and/or cancer. Stages of development are given and indications for treatment are based upon clinical trials information at clinicaltrials.gov. Where available, references are given for the chemical structures of these compounds.

CompoundCompanyTargetStatusIndicationsStructure Reference
PI3K inhibitors
    XL147Exelixis/SanofiPI3KPhase I/IISolid tumors/lymphomaN.A.
    PX-866OncothyreonPI3KPhase I/IISolid tumorsIhle et al., 2004
    GDC0941Genentech/RochePI3KPhase ISolid tumors/non-Hodgkin lymphomaFolkes et al., 2008
    BKM120NovartisPI3KPhase I/IISolid tumors/leukemiaKoul et al., 2012
    ZSTK474Zenyaku KogyoPI3KPhase INeoplasmsYaguchi et al., 2006
    GS-1101 (CAL-101)GileadPI3KδPhase IINon-Hodgkin lymphoma/leukemia/allergic rhinitisIkeda et al., 2010
    BYL719NovartisPI3KαPhase ISolid tumorsN.A.
    INK1117IntellikinePI3KαPhase ISolid tumorsN.A.
    IPI-145InfinityPI3Kα/γPhase IAdvanced hematologic malignanciesN.A.
Akt inhibitors
    PerifosineKeryxAktPhase IIIColorectal cancer/multiple myelomaYap et al., 2008
    MK2206MerckAktPhase I/IISolid tumorsHers et al., 2011
PI3K/mTOR inhibitors
    BEZ235NovartisPI3K/mTORPhase I/IISolid tumorsMaira et al., 2008
    BAY80-6946BayerPI3K/mTORPhase INeoplasmsN.A.
    BGT226NovartisPI3K/mTORPhase ISolid tumorsChang et al., 2011
    XL765Exelixis/SanofiPI3K/mTORPhase ISolid tumorsN.A.
    SF1126Semafore PharmaPI3K/mTORPhase ISolid tumors/multiple myelomaGarlich et al., 2008
    GSK2126458GSKPI3K/mTORPhase ISolid tumorsKnight et al., 2010
    PF-04691502PfizerPI3K/mTORPhase I/IISolid tumors
    GDC-0980Genentech/RochePI3K/mTORPhase I/IISolid tumors/non-Hodgkin's lymphoma/renal carcinomaSutherlin et al., 2011
    PKI-587PfizerPI3K/mTORPhase INeoplasmsVenkatesan et al., 2010
mTOR inhibitors
    OSI-027OSI PharmamTOR/catalytic sitePhase ISolid tumors/lymphomaBhagwat et al., 2011
    AZD8055AstraZenecamTOR/catalytic sitePhase I/IISolid tumors/lymphomaChresta et al., 2010
    INK128IntellikinemTOR/catalytic sitePhase ISolid tumors/multiple myelomaN.A.
    RidaforolimusAriad/MerckmTORC1Phase IIIMetastatic soft-tissue and bone sarcomasYap et al., 2008
    EverolimusNovartismTORC1ApprovedRenal cell carcinoma/neuroendocrine tumors/subependymal giant cell astrocytomaYap et al., 2008
    TemsirolimusWyethmTORC1ApprovedRenal cell carcinomaYap et al., 2008
SHIP-1 activator
    AQX-1125AquinoxSHIP-1Phase IIAirway inflammationN.A.

  • N.A., not available; AZD8055, (5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol; BAY80-6946, 2-amino-N-(7-methoxy-8-(3-morpholinopropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyrimidine-5-carboxamide; BEZ235 (2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1-yl)phenyl]propanenitrile) BGT226, 8-(6-methoxypyridin-3-yl)-3-methyl-1-(4-piperazin-1-yl-3-trifluoromethylphenyl)-1,3-dihydroimidazo(4,5-c)quinolin-2-one; GDC-0980, 1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno(3,2-d)pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one; GSK2126458, 2,4-difluoro-N-(2-(methyloxy)-5-(4-(4-pyridazinyl)-6-quinolinyl)-3-pyridinyl)benzenesulfonamide; OSI-027, 4-[(5Z)-4-amino-5-(7-methoxyindol-2-ylidene)-1H-imidazo[5,1-f][1,2,4]triazin-7-yl]cyclohexane-1-carboxylic acid; PF-04691502, 2-amino-8-(4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido(2,3-d)pyrimidin-7(8H)-one; PKI-587, 1-(4-((4-(dimethylamino)piperidin-1-yl)carbonyl)phenyl)-3-(4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl)urea 1,3,4,7,10,11,12,13,14,15,16,17-dodecahydro-2-oxa-cyclopenta(a)phenanthren-11-yl)ester; XL765, N-[4-[[3-(3,5-dimethoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl]-3-methoxy-4-methylbenzamide.