mtorc1

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.

Autogramin-1 potently inhibits autophagy induced by mTORC1 inhibition (Rapamycin; IC50: 0.44 μM) or starvation (IC50: 0.17 μM).

NV-5138 is a selective, orally active intracerebral mTORC1 agonist that binds to Sestrin2. It is a leucine analog. It can be used in biological studies of antidepressants.

Cbz-B3A is a potent inhibitor of mTORC1 signalling, inhibits phosphorylation of eIF4E-binding protein 1 (4EBP1) and blocks translation by 68%.

Indoximod (NLG-8189) is a methylated tryptophan with immune checkpoint inhibitory activity. Indoximod inhibits the enzyme indoleamine 2, 3-dioxygenase (IDO), which degrades the essential amino acid tryptophan, and may increase or maintain tryptophan levels important to T cell function. Tryptophan depletion is associated with immunosuppression involving T cell arrest and anergy.

PQR620 is a novel potent and selective, brain penetrant inhibitor of mTORC1/2.

FT-1518 is an orally available, selective and potent mTORC1 and mTORC2 inhibitor with anticancer and antitumor activity for cancer research.

Dactolisib Tosylate (BEZ235 Tosylate) is a dual kinase inhibitor targeting PI3K and mTOR, with IC50 values of 4, 75, 7, and 5 nM for PI3Kα, β, γ, and δ, respectively. It also inhibits mTORC1 and mTORC2.

MT 63-78 is a specific and effective direct AMPK activator (EC50: 25 μM) that blocks prostate cancer growth by inhibiting the lipogenesis and mTORC1 pathways. It has antitumor effects and induces cell mitotic arrest and apoptosis.

PQR530 is a highly potent dual pan-PI3K/mTORC1/2 inhibitor. PQR530 inhibited protein kinase B (PKB, pSer473) and ribosomal protein S6 (pS6, pSer235/236) phosphorylation with IC50 values of 0.07 μM. It also showing antitumor activity.

Rheb inhibitor NR1 is a selective mTORC1 inhibitor that suppresses the phosphorylation of T389pS6K1 and enhances the phosphorylation of S473pAKT.

Omipalisib (GSK2126458) is a small-molecule pyridylsulfonamide inhibitor of phosphatidylinositol 3-kinase (PI3K) with potential antineoplastic activity.

Torkinib (PP 242) (PP 242) is a selective and ATP-competitive mTOR inhibitor (IC50: 8 nM). It also inhibits mTORC1/2 (IC50s: 30/58 nM).

KU-0063794 is a potent and highly specific dual inhibitor of mTORC1 and mTORC2.

PIK-93, the first potent synthetic PI4K inhibitor, exhibits an IC50 of 19 nM and also inhibits PI3Kα with an IC50 of 39 nM.

Palomid 529 (SG 00529) has been used in trials studying the treatment of Age-Related Macular Degeneration.

Timosaponin AIII (Timosaponin A3) induces autophagy in HeLa cells followed by apoptotic cell death (IC50: 10 μM). The Timosaponin AIII cellular response is mediated via inhibition of mTORC1 and induction of ER stress (IC50: 2.5 μM, BT474 cells; 6 μM, MDAMB231). The Timosaponin AIII pro-apoptotic response is selective for tumor cells over normal cells but autophagy is induced in both.

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].

AZD 3147 is an inhibitor of mTORC with IC50s of 40.7 and 5.75 nM for mTORC1 and mTORC2. AZD 3147 shows IC50s of 912, 5495, 9333, and 6310 nM for PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ, respectively.

TCS-PIM-1-4a (SMI-4a), a Pim inhibitor, blocks mTORC1 activity through activation of AMPK and kills a wide range of both myeloid and lymphoid cell lines (IC50=0.8-40 μM).

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

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.

Pelitrexol (AG2037) is a GARFT inhibitor, which can inhibit the activity of mTORC1, reduce intracellular guanine nucleotides and block the cell cycle in the s-phase, with antiproliferative activity, and can be used in non-small cell lung cancer.