Scientifica

Review Article

mTOR Inhibition: From Aging to Autism and Beyond

Table 1

Some mTOR inhibitors used clinically and in research.


Chemical	Class	Clinical uses/trials	References

Rapamycin Sirolimus Rapamune	Rapalogue	FDA approved to prevent organ rejection following renal transplant and for use in drug eluting stents to prevent restenosis following angioplasty. Orphan drug status for bone sarcoma, tuberous sclerosis, and uveitis. Multiple active, recruiting, and completed trials.	[35, 62, 63]
Everolimus RAD001 Afinitor Zortress	Rapalogue	FDA approved for subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis, specific forms of breast and pancreatic cancer, advanced renal cell carcinoma, noncancerous kidney tumors, and renal and liver transplants. Multiple active, recruiting, and completed trials. Orphan drug status for lymphoplasmacytic lymphoma and gastric cancer.	[62, 63]
Temsirolimus CCI-779 Torisel	Rapalogue	FDA approved for advanced stage renal cell carcinoma. Multiple active, recruiting, and completed trials.	[62, 63]
Ridaforolimus AP23573 MK-8669 Deforolimus	Rapalogue	Multiple active, recruiting, and completed trials for various cancers.	[64]
Zotarolimus ABT-578	Rapalogue	FDA approved for use in cardiac stents to prevent restenosis following angioplasty. Multiple active and completed trials.	[65, 66]
AZD8055	ATP-competitive mTOR inhibitor	In clinical trials for gliomas, liver cancer, and solid tumors.	[67–70]
AZD2014	ATP-competitive mTOR inhibitor	Clinical trials recruiting for metastatic breast and renal cancers.	[67]
OSI-027	ATP-competitive mTOR inhibitor	Completed phase 1 clinical trial in patients with advanced solid tumors or lymphoma.	[71, 72]
MLN0128	ATP-competitive mTOR inhibitor	Completed and recruiting phase 1 trials for multiple myeloma and advanced malignancies.	[72]
WYE-132	ATP-competitive mTOR inhibitor	None.	[73]
Torin1	ATP-competitive mTOR inhibitor	None.	[74]
PI-103	PI3K/mTOR inhibitor	None.	[75]
P7170	PI3K/mTOR inhibitor	Phase 1 clinical trial recruiting for advanced refractory solid tumors.	[76]
PF-04691502	PI3K/mTOR inhibitor	Phase 1 trials completed and recruiting; phase 2 trial for recurrent endometrial cancer recruiting.	[77]
PF-05212384 PKI-587	PI3K/mTOR inhibitor	Phase 1 clinical trials recruiting for advanced cancers; phase 2 trial for recurrent endometrial cancer recruiting.	[78, 79]
GNE477	PI3K/mTOR inhibitor	None.
PKI-179	PI3K/mTOR inhibitor	Phase 1 clinical trial terminated.	[80]
WJD008	PI3K/mTOR inhibitor	None.
XL765 SAR245409	PI3K/mTOR inhibitor	Several phase 1 trials completed for solid tumors, breast cancer, malignant gliomas, and recurrent glioblastomas.	[81]
NVP-BEZ235	PI3K/mTOR inhibitor	Multiple phase 1 trials completed. Phase 1/2 trials active, ongoing, or recruiting for various cancers.	[82, 83]
BGT226		Phase 1 and phase 1/2 trials completed for solid tumors and breast cancer.	[84, 85]
SF1126		Phase 1 trial completed for solid tumors.	[86]
GSK2126458	PI3K/mTOR inhibitor	Active and recruiting phase 1 trials for solid tumors.	[72, 83]

Current clinical trials information from clinical trials.gov on September 12, 2013. 1507 studies returned for “rapamycin,” “everolimus,” “sirolimus,” or “temsirolimus.” “None” means no hits returned.