mammalian target of rapamycin

AZD8055 is an ATP-competitive mTOR inhibitor (IC50: 0.8 nM in MDA-MB-468 cells). It is ~1,000-fold selective for mTOR over all PI3K isoforms.

Rapamycin (AY 22989) is a natural product of macrolides, an mTOR inhibitor with specificity (HEK293 cells: IC50=0.1 nM). Rapamycin has immunosuppressive activity and induces autophagy.

Torin 1 is an effective inhibitor of mTORC1 2 with (IC50: 2 nM 10 nM); has 1000-fold selectivity for mTOR than PI3K.

MHY1485 is an mTOR activator that is cell-permeable. MHY1485 inhibits autophagosome and lysosome fusion, leading to accumulation of LC3II proteins and increased autophagosomes, thereby inhibiting cellular autophagy.

WYE-125132 (WYE-132 (WYE-125132)) is a highly potent, ATP-competitive mTOR inhibitor with IC50 of 0.19 nM; highly selective for mTOR versus PI3Ks or PI3K-related kinases hSMG1 and ATR.

WAY-600 is a potent, ATP-competitive, and selective inhibitor of mTOR with an IC50 of 9 nM; it blocks mTORC1 P-S6K(T389) and mTORC2 P-AKT(S473) but not P-AKT(T308), and is selective for mTOR over PI3Kα (>100-fold) and PI3Kγ (>500-fold).

mTOR inhibitor-3 is a selective mTOR inhibitor (Ki= 1.5 nM). mTOR inhibitor-3 inhibits mTORC1 and mTORC2 in cellular and in vivo experiments.

GDC-0349 (RG-7603) is a potent and selective ATP-competitive inhibitor of mTOR with Ki of 3.8 nM, 790-fold inhibitory effect against PI3Kα and other 266 kinases. Phase 1.

(+)-Usnic acid (D-Usnic Acid) is a naturally occurring dibenzofuran derivative found in several lichen species.

L-Leucine ((S)-Leucine) is one of nine essential amino acids in humans (provided by food), L-Leucine is important for protein synthesis and many metabolic functions. L-Leucine contributes to regulation of blood-sugar levels; growth and repair of muscle and bone tissue; growth hormone production; and wound healing. L-Leucine also prevents breakdown of muscle proteins after trauma or severe stress and may be beneficial for individuals with phenylketonuria. L-Leucine is available in many foods and deficiency is rare.

PP-121 is a multi-targeted inhibitor of PDGFR (IC50: 2 nM), Hck (IC50: 8 nM), mTOR (IC50: 10 nM), VEGFR2(IC50: 12 nM), Src (IC50: 14 nM) and Abl (IC50: 18 nM) , also inhibits DNA-PK (IC50: 60 nM).

OSI-027 (ASP4786) is a selective and potent dual inhibitor of mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM, and more than 100-fold selectivity observed for mTOR than PI3Kα, PI3Kβ, PI3Kγ or DNA-PK. Phase 1.

PF-04691502 is a potent and selective inhibitor of PI3K and mTOR kinases with antitumor activity.

Dactolisib (BEZ235) is an orally bioavailable inhibitor of PI3K and mTOR, with IC50 values of 4 nM for p110α, 5 nM for p110γ, 7 nM for p110δ, 75 nM for p110β, and 20.7 nM for mTOR.

Everolimus (SDZ-RAD) is a potent mTOR inhibitor that binds to FKBP-12. It is used alone or in combination with calcineurin inhibitors.

Vistusertib (AZD2014) is an orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity.

ETP-46464 is an effective and specific ATR inhibitor (IC50: 25 nM).

XL388 is a highly effective, specifc, ATP-competitive inhibitor of mTOR ( IC50: 9.9 nM), 1000-fold selectivity than the closely related PI3K kinases.

Torin 2(IC50=0.25 nM), a specific and effective mTOR inhibitor, is the 800-fold greater specific activity for mTOR than PI3K and improves pharmacokinetic properties. The EC50 of Torin 2 for ATM ATR DNA-PK inhibition is 28 nM 35 nM 118 nM, respectively.

KU-0060648 is a dual inhibitor of DNA-PK and PI3Kα, PI3Kβ, PI3Kδ with IC50 values of 8.6 nM, 4 nM, 0.5 nM, and 0.1 nM respectively, and demonstrates less inhibition of PI3Kγ with an IC50 of 0.59 μM.

MTI-31 (LXI-15029) is a potent, orally active, and highly selective inhibitor of mTORC1 and mTORC2, exhibiting a Kd of 0.20 nM for mTOR and >5,000-fold selectivity over PIK3CA, PIK3CB, and PIK3G in binding assays, with an IC50 of 39 nM for mTOR in a LANCE assay of mTOR substrate phosphorylation with 100 μM ATP [1].

WYE-687 is an ATP-competitive and selective inhibitor of mTOR with an IC50 of 7 nM; it blocks mTORC1 pS6K(T389) and mTORC2 P-AKT(S473) without affecting P-AKT(T308). Its selectivity for mTOR is greater than PI3Kα (>100-fold) and PI3Kγ (>500-fold).

VS-5584 (SB2343) is a pan-PI3K mTOR kinase inhibitor.

Bimiralisib (PI3K-IN-2) is an orally bioavailable pan inhibitor of PI3K and inhibitor of the mTOR, with potential antineoplastic activity. PI3K-IN-2 inhibits the PI3K kinase isoforms alpha, beta, gamma and delta and, to a lesser extent, mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in cells overexpressing PI3K mTOR. Activation of the PI3K mTOR pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy.