Table 1.

Drugs inhibiting the PI3K/AKT/mTOR pathway that were in early clinical stages in 2012 and their current status

DrugCompanyTarget(s)Status in 2012Current statusa
PI3K–mTOR inhibitors
 WortmanninPI3K, mTOR, DNA-PK, MAPKPreclinicalDiscontinued
 (NVP)-BGT226NovartisPI3K, mTORPhase IDiscontinued
 (NVP)-BEZ235/dactolisibNovartisPI3K, mTORPhase I, IIDiscontinued
 XL765/SAR254409/voxtalisibExelixis/Sanofi-AventisPI3K, mTORPhase IDiscontinued
 GDC-0980/apitolisibGenentechPI3K, mTORPhase IDiscontinued
 PI-103Piramed Pharma/RochePI3K, mTORC1/2, DNA-PKPreclinicalDiscontinued
 GSK1059615GlaxoSmithKlinePI3K, mTOR, DNA-PKPhase IDiscontinued
 PKI-587/PF-05212384/gedatolisibPfizerPI3K, mTORPhase IActive (2 trials)
 PF-04691502PfizerPI3K, mTORPhase IDiscontinued
Pan-PI3K inhibitors
 (NVP)-BKM120/buparlisibNovartisPI3KPhase I, IINo further active development
 LY294002LillyPI3K, other related kinasesPreclinicalDiscontinued
 SF1126SemaforePI3K and mTORPhase IDiscontinued
 PWT-458Wyeth/PfizerPI3KPreclinicalDiscontinued
 PX-866Oncothyreon Inc.PI3KPhase IDiscontinued
 XL-147/SAR245408/pilaralisibExelixis/Sanofi-AventisPI3KPhase IDiscontinued
 ZSTK474Zenyaku Kogyo Co. Ltd.PI3KPreclinicalDiscontinued
 GSK615/GSK1059615GlaxoSmithKlinePI3KPhase IDiscontinued
 CH5132799Chugai Pharma Europe Ltd.PI3KPhase IDiscontinued
 GDC-0941/pictilisibPIramed Pharma/GenentechPI3K, FLT3Phase IDiscontinued
 BAY 80-6946/copanlisibBayerPI3KPhase IActive (10 trials)
Isoform-specific PI3K inhibitors
 CAL-101/idelalisibCalistoga PharmaceuticalsPI3K (p110δ)Phase IApproved
 BYL719/alpelisibNovartisPI3K (p110α)Phase IActive (17 trials)
INK1117/TAK-117/serabelisibIntellikine/Millennium PharmaceuticalsPI3K (p110α)Phase IActive (1 trial)
 AS-252424Merck SeronoPI3K (p110γ)PreclinicalDiscontinued
 GSK2636771GlaxoSmithKlinePI3K (p110β)Phase IActive (14 trials)
 TGX-221Alexis/Enzo Life Sciences Inc.PI3K (p110β)PreclinicalDiscontinued
 GDC0032/taselisibGenentechPI3K (p110α, δ, γ)Phase IActive (5 trials)
AKT inhibitors
 Perifosine/KRX-0401AEterna Zentaris Inc./Keryx BiopharmaceuticalsAKT, MEK 1/2, ERK 1/2, JNKPhase I, IIDiscontinued
 Triciribine/API-2VioQuest PharmaceuticalsAKT 1, 2, 3Phase IActive (3 trials)
 GDC-0068/ipatasertibRoche/GenentechAKT 1, 2, 3Phase IActive (2 trials)
 SR13668SRI InternationalAKTPreclinicalDiscontinued
 AR-67/DB-67Arno TherapeuticsAKTPhase I, IIDiscontinued
 AR-42Arno TherapeuticsAKTPreclinicalDiscontinued
 GSK690693GlaxoSmithKlineAKT 1, 2, 3Phase IDiscontinued
 KP372-1QLT Inc.AKT, PDK1, FLT3PreclinicalDiscontinued
 VQD-002/API-2VioQuest PharmaceuticalsAKTPhase I, IIDiscontinued
 A-443654Abbott LaboratoriesAKTPreclinicalDiscontinued
 XL-418ExelixisAKT/p70S6KPhase IDiscontinued
 MK-2206MerckAKT 1, 2, 3Phase IActive (2 trials)
TORC1 inhibitors (rapalogs)
 Rapamycin/sirolimusWyeth/PfizermTORC1Phase I, IIApproved
 CCI-779/temsirolimusWyeth/PfizermTORC1Phase I, IIApproved
 RAD001/everolimusNovartismTORC1Phase I, IIApproved
AP-23573/ridaforolimus/deforolimusAriad/MerckmTORC1Phase I, IINo further active development
TORC1/2 inhibitors
 AZD-8055AstraZenecamTORC1/mTORC2Phase I, IIDiscontinued
 AZD2014AstraZenecamTORC1/mTORC2Phase I, IIActive (29 trials)
 OSI-027OSI PharmaceuticalsmTORC1/mTORC2Phase IDiscontinued
 INK-128/MLN0128/TAK228IntellikinemTORC1/mTORC2Phase IActive (17 trials)
 PP-242UCSFmTORC1/mTORC2Phase IDiscontinued
 CC-223CelgenemTORC1/mTORC2, DNA-PKPhase IActive (1 trial)