Table 2.
Mechanistic Target of Rapamycin (mTOR) inhibitors and their mode of inhibition.
| mTOR Inhibitor | Mechanism of Action | Protein Inhibition * | References | Current Clinical Timeline |
|---|---|---|---|---|
| Rapamycin | Destabilizes the mTOR-Raptor complex | MYC | [69,70] | Phase 1 through 4 clinical trials in multiple cancers (solid organ, hematopoietic cancers) |
| CCI-779 (Temsirolimus) | Cyclin-D1, Cyclin-D3, MYC | [64,71,72] | ||
| RAD001 (Everolimus) | MYC, Cyclin D1 | [66,73,74] | ||
| Icariside II | mTOR Kinase inhibitor | MYC | [60] | Preclinical testing only |
| BEZ235 | mTOR Kinase inhibitor | Cyclin A, Cyclin D1, Parp, Caspase 3, MYC | [75,76] | Phase 1 through 3 clinical trials in breast, prostate, renal tumors |
| MTI-31 | mTOR Kinase inhibitor | p-Akt, Cyclin D1, MYC | [77] | Preclinical testing only |
| AZD8055 | mTOR Kinase inhibitor | MYC, Mcl-1, c-Jun, Cyclin E | [78] | Phase 1/2 clinical trials in advanced solid tumors, lymphomas etc. |
| MLN0128 (INK128) | mTOR Kinase inhibitor | 4EBP1, p-S6K1, MYC | [79,80] | Phase 1/2 clinical trials in thyroid, lung, endometrial, breast, myeloma, lymphoma etc. |
| PI-103 | mTOR Kinase inhibitor | MYC, Cyclin D3, PI3K, p-Akt | [77,81] | Preclinical testing only |
| PP242 | mTOR Kinase inhibitor | MYC, Cyclin D1 | [82] | Preclinical testing only |
| OSI-027 | mTOR Kinase inhibitor | MYC | [80] | Phase 1 clinical trial in advanced solid tumors & lymphoma |
* Indirect translational down regulation of different proteins by mTOR inhibitors as per the previous literature. MCL1: Myeloid Leukemia Cell Differentiation Protein 1; 4EBP1: Eukaryotic Translation Initiation Factor 4E-Binding Protein 1; S6K: Ribosomal Protein S6 Kinase Beta-1; PI3K: Phosphatidyl-4,5-bisphosphate 3’ Kinase; AKT: Protein Kinase B.