PP-242 is a selective mTOR inhibitor with IC50 of 8 nM. mTOR has emerged as an important drug target, and PP-242 is the first selective and ATP competitive inhibitor of mTOR that has been described. Unlike rapamycin, PP-242 inhibits both mTORC1 and mTORC2. PP-242 suppresses bladder cancer cell proliferation and migration through deactivating the mammalian target of rapamycin complex 2/AKT1 signaling pathway. PP242 also inhibits several protein kinases including PKC, RET and JAK2 kinases. PP-242 shows strong antitumor activity in a pheochromocytoma PC12 cell tumor model. PP-242 suppresses cell proliferation, metastasis, and angiogenesis of gastric cancer through inhibition of the PI3K/AKT/mTOR pathway. PP-242 induces apoptosis in AML cells under conditions mimicking the bone marrow microenvironment.

PF-04979064 is a highly potent and orally bioavailable PI3K/mTOR dual inhibitor developed through structure-based drug design. It inhibited mTOR, PI3Kα, β, δ and γ isoforms and AKT phosphorylation with IC50 as 2.64 nM, 0.395 nM, 0.111 nM, 0.122 nM and 28.3 nM, respectively. PF-04979064 exhibited cellular potency with an IC50 of 9.1 nM in a BT20 cell assay. PF-04979064 exhibited excellent in vitro potency, very good solubility, high LipE, excellent kinome selectivity, robust PK/PD correlation and tumor growth inhibition (TGI) in a U87MG mouse xenograft model, and acceptable predicted human clearance after incorporating both CYP- and AO-mediated metabolism. PF-04979064 is the back-up candidate to PF-04691502 which is in Phase I/II clinical trials for treating solid tumors.

PKI-402 is a reversible, ATP-competitive, and equipotent inhibitor of class I PI3Ks, including the E545K and H1047R PI3K-α mutants, and mTOR (IC50 versus PI3K-α = 2 nmol/L). Selectivity of PKI-402 was established in a screen against 236 diverse human kinases. PKI-402 caused in vitro growth inhibition of human tumor cell lines derived from a diverse set of human tumor tissues, including breast, brain (glioma), pancreas, and non–small cell lung cancer (NSCLC) tissues. In vivo, PKI-402 displayed antitumor activity (i.v. route) in breast [MDA-MB-361: Her2+ and PIK3- CA (E545K)], glioma (U87MG and PTEN), and NSCLC (A549; K-Ras and STK11) xenograft models. PKI-402 may be useful either as a single agent or in combination with cytostatic or cytotoxic (e.g., temozolomide) drugs in treatment of glioblastoma multiforme.

CGP60474 is a promising inhibitor of CDK1 with a high degree of selectivity versus other serine/threonine and tyrosine kinases and show competitive kinetics relative to ATP.

GNE-493 is a potent, selective, and orally available pan-PI3-kinase and dual pan-PI3-kinase/mTOR inhibitor for the treatment of cancer.

GNE-477 is a potent and efficacious dual PI3K/mTOR inhibitor. GNE-477 exhibited stasis in a PC3 tumor growth inhibition study.

KU-0063794 was originally developed as part of the Kudos Biochemical experimental program, Pfizer in 2009 bought Kudos Biochemicals for its pipeline portfolio; KU has not been clinically developed since then. KU-0063794 is a highly specific inhibitor against mTOR 1 and 2 with IC50 of approximately 3-100 nM for mTOR1 and 2 depending on which cell line is tested. KU-0063794 dis played no activity at PI 3-kinase or 76 other kinases tested, it Inhibits activation and hydrophobic motif phosphorylation of Akt, S6K and SGK, but not RSK, in addition, this compound suppresses cell growth and induces G1 cell cycle arrest in vitro. Ku-0063794 was effective in decreasing the viability and growth of renal cell carcinoma, Caki-1 and 786-O, in vitro by inducing cell cycle arrest and autophagy, but not apoptosis. In addition, experiments in vitro showed that Ku-0063794 possessed therapeutic potential for the treatment of keloid disease and acute lymphoblastic leukemia.

Umirolimus (Biolimus A9), an analogue of sirolimus, is a highly lipophilic macrolide compound developed by Biosensors International as an antiproliferative agent in coronary artery restenosis. Umirolimus has immunosuppressive and anti-inflammatory effects. It is used for the prevention of restenosis.