Review Article

Potential Therapeutic Roles for Inhibition of the PI3K/Akt/mTOR Pathway in the Pathophysiology of Diabetic Retinopathy

Table 2

Principal PI3K/Akt/mTOR Inhibitors in clinical development.

Name and general classificationManufacturer or sourceClinical stageIndication

Akt inhibitors
SF1126 (RGD peptide + LY294002 a morpholino derivative of quercetin)Semaphore PharmaceuticalsPhase 1Chronic lymphocytic leukemia
Perifosine (KRX-0401)Keryx Biopharmaceuticals, IncPhase 2 and Phase 3Colorectal cancers; multiple myeloma; other multiple cancer types
PX-866OncothyreonPhase 1 & 2Solid tumor disease; Glioblastoma
Triciribine (API-2; TCN-PM; VD-0002)VioQuest PharmaceuticalsPhase 1p-AKT-positive solid malignancies
Rapamycin (and analogs)
Everolimus (RAD001; Zortress; Afinitor)Novartis Pharma AGMarketed 2009Advanced renal cell carcinoma after failure with sunitinib or sorafenib; subependymal giant cell astrocytoma (SEGA)
Deforolimus (AP23573; MK-8669; Ridaforolimus)ARIAD Pharmaceuticals; MerckPhase 3 (SUCCEED TRIAL)Metastatic soft-tissue and bone sarcomas
Sirolimus (Rapamycin; MSR001; Rapamune; Perceiva)Santen Inc; MacuSight, Inc.Wyeth PharmaceuticalsNovember 2010Prophylaxis of organ rejection in patients >13 years old receiving kidney transplant
Temsirolimus (CCI-779; TORISEL)Wyeth PharmaceuticalsMarketed 2007Advanced renal cell carcinoma
Dual mTOR inhibitors
AZD8055Astra ZenecaMultiple Phase 1 and multiple Phase 2Advanced hepatocellular carcinoma; advanced solid malignancies and lymphomas
NVP-BEZ235Novartis Pharma AGPancreatic cancer
WYE-125132Wyeth PharmaceuticalsMultiple Phase 1 and Phase 2Advanced malignancies
Palomid 529Paloma Pharmaceuticals Inc.Phase 1Age related macular degeneration (intravitreal and conjunctival administration)
PKI-179Pfizer; WyethPhase 1Advanced malignant solid tumors
PKI-402Pfizer
PKI-587 (PF-05212384)PfizerPhase 1Incurable cancer
Natural mTOR inhibitors
Epigallocatechin gallate (EGCG) (flavonoid polyphenol)Green teaPre-clinicalPending
CaffeineMultiple and variedPre-clinicalPending
CelastrolThunder of God vine (Tripterygium wilfordii)Pre-clinicalPending
Curcumin (diferuloylmethane)Indian spice turmericPre-clinicalColon cancer (?)
Hispidulin (flavonoid molecule)Artemisia vestita Saussurea involucratePre-clinicalPending
ResveratrolSkin of red grapesPre-clinicalPending

*Note references used to compile table include: Drugs.com, Searchmedica.com, Clinicaltrials.gov, PubMed.gov, and FDA product information inserts when available.