Table 1 mTOR inhibitors. The rapamycin category includes rapamycin (sirolimus) and its analogs: temsirolimus (CCI-779), everoliums (RAD001), and deforolimus (AP23573). PI3K indicates the p110α isoform. PI-103 and XL765 also inhibit DNA-PK (IC50 of 2 nM for PI-103; IC50 of 150 nM for XL765).
DrugStructureBinding siteMechanism of actionmTORC1 (IC50)mTORC2 (IC50)PI3K (IC50)References
RapamycinsMacrolide estermTOR FRB domain (adjacent to kinase domain)Functions when bound to the immunophilin FKBP12

Partial mTORC1 inhibitor

Cell-type specific mTORC2 inhibitor
<10 nMReviewed in (10)
Torin1PyridinonequinolinemTOR ATP-binding pocketmTOR kinase inhibitor<10 nM<10 nM1.8 μM(13)
PP242PyrazolopyrimidinesmTOR ATP-binding pocketmTOR kinase inhibitor<10 nM<10 nM1.96 μM(14)
PP30PyrazolopyrimidinesmTOR ATP-binding pocketmTOR kinase inhibitor<100 nM<100 nM3.0 μM(14)
NVP-BEZ235ImidazoquinazolinemTOR/PI3K ATP-binding pocketDual kinase inhibitor of mTOR and PI3K<10 nM<10 nM<10 nM(23)
PI-103Tricyclic pyridofuropyrimidinemTOR/PI3K ATP-binding pocketDual kinase inhibitor of mTOR and PI3K20 nM83 nM8 nM(36)
XL765Not availablemTOR/PI3K ATP-binding pocketDual kinase inhibitor of mTOR and PI3K157 nM*157 nM*39 nMReviewed in (22)

*Based on immunoprecipitation kinase assays.