mTOR
The mammalian target of rapamycin (mTOR; EC 2.7.11.1), a phosphoinositide 3-kinase-related protein kinase, controls cell growth in response to energy, nutrients, growth factors and other environmental cues, and it figures prominently in cancer. It belongs to the phosphoinositide 3-kinase (PI3K)-related protein kinase (PIKK) family. mTOR assembles into two complexes with distinct inputs and downstream effects. mTOR complex 1 (mTORC1) is defined by its RAPTOR subunit which is replaced by RICTOR in mTOR complex (mTORC2).
mTORC1 regulates cell growth by promoting translation, ribosome biogenesis and autophagy. Its activation requires nutrients and amino acids, which result in the RAPTOR-mediated recruitment of mTORC1 to lysosomes and late endosomes, and co-localization with its activator, the small GTPase RHEB. mTORC1 substrates include the eIF4E-binding protein 1 (4E-BP1) and ribosomal S6 kinases (S6K).
mTORC2 responds primarily to growth factors, promoting cell-cycle entry, cell survival, actin cytoskeleton polarization and anabolic output. Its substrates include the Ser/Thr protein kinases Akt, SGK and PKC, which share the hydrophobic motif phosphorylation site with S6K1.
Noteworthy, rapamycin, which forms a ternary complex with the FK506-binding protein 12 (FKBP12) and the FRB domain of mTOR, is thought to be an allosteric inhibitor. Rapamycin–FKBP12 inhibits mTORC1 to a variable extent that is substrate and phosphorylation-site dependent, while it does not bind to mTORC2[1],[2].
Axon Ligands™ that block mTOR activity are also listed in the section for PI3K/AKT/mTOR signaling.
[1] mTOR kinase structure, mechanism and regulation. H. Yang et al. Nature 2013, 497, 217-223.
[2] mTOR: a protein kinase switching between life and death. L. Asnaghi, P. Bruno, M. Priulla, A. Nicolin. Pharmacol. Res. 2004, 50, 545-549.
| Axon ID | Name | Description | From price | |
|---|---|---|---|---|
| 3996 | AZD2014 | Orally bioavailable dual mTORC1/mTORC2 inhibitor | Inquire | |
| 1561 | AZD8055 | mTOR inhibitor | €80.00 | |
| 1281 | BEZ 235 | PI3K and mTOR tyrosine kinase inhibitor | €50.00 | |
| 2630 | eCF309 | Highly selective and potent inhibitor of mTOR signalling | €85.00 | |
| 4149 | Everolimus | Selective and orally active mTOR1 inhibitor | Recently added | Inquire |
| 1782 | GDC 0980 | Dual PI3K and mTOR inhibitor | €80.00 | |
| 3584 | GDC-0084 | Brain-penetrant dual PI3K and mTOR inhibitor | €110.00 | |
| 1596 | GSK 2126458 | Dual PI3K and mTOR inhibitor | €50.00 | |
| 2142 | INK 128 | Potent and selective mTOR inhibitor | €110.00 | |
| 1472 | KU-0063794 | mTOR inhibitor | €60.00 | |
| 2425 | MHY 1485 | mTOR activator with an inhibitory effect on autophagy | €70.00 | |
| 3628 | MHY-1685 | mTOR inhibitor; Senescence inhibitor | €50.00 | |
| 2029 | NVP-BGT226 | Orally active dual PI3K/mTOR inhibitor | €120.00 | |
| 1718 | Palomid 529 | mTOR inhibitor | €90.00 | |
| 1855 | PF 04691502 | PI3K and mTOR tyrosine kinase inhibitor | €90.00 | |
| 1807 | PKI 587 | Dual PI3K and mTOR inhibitor | €90.00 | |
| 2069 | Rapamycin | Specific inhibitor of mTOR; binds to FKBP12 | €85.00 | |
| 5007 | Stem Cell 5i inhibitor Set | Set of five inhibitors for neural differentiation of human pluripotent stem cells. | €200.00 | |
| 1699 | Temsirolimus | mTOR inhibitor | €95.00 | |
| 1833 | Torin 1 | mTOR inhibitor | €90.00 | |
| 1834 | Torin 2 | mTOR inhibitor | €90.00 | |
| 3794 | Urolithin A | Inhibitor of the PI3K/AKT/mTOR pathway | €70.00 | |
| 2951 | XL 388 | Highly potent, selective, ATP-competitive, and orally bioavailable mTOR inhibitor | €125.00 | |
| 1706 | XL PI3K/mTOR inhibitor | Dual PI3K and mTOR kinase inhibitor | €120.00 | |
| 4009 | XL-765 | Potent and selective PI3K / mTOC inhibitor | Inquire | |