mTORC2 Inhibitor

Torin 1 is a potent inhibitor of mTOR with an IC₅₀ of 3 nM. Torin 1 inhibits both mTORC1/2 complexes with IC₅₀ values between 2 and 10 nM. Torin 1 is an effective inducer of autophagy.

AZD-8055 is a potent, selective, and orally bioavailable ATP-competitive mTOR kinase inhibitor with an IC₅₀ of 0.8 nM. AZD-8055 inhibits both mTORC1 and mTORC2.

Sapanisertib (INK-128; MLN0128; TAK-228) is an orally active dual mTORC1/mTORC2 inhibitor. Sapanisertib directly and simultaneously inhibits mTORC1/2 activity through competitive binding with ATP, thereby comprehensively blocking downstream processes such as protein and lipid synthesis and cytoskeletal reorganization, consequently suppressing tumor cell proliferation and promoting apoptosis. Sapanisertib is applicable to research on melanoma, ovarian cancer, pulmonary fibrosis, and hematological malignancies.

Dactolisib (BEZ235) is an orally active and dual pan-class I PI3K and mTOR kinase inhibitor with IC₅₀s of 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR, respectively. Dactolisib (BEZ235) inhibits both mTORC1 and mTORC2.

JPS004 is a PROTAC degrader targeting HDAC1, HDAC2 and HDAC3. JPS004 induces extensive transcriptomic changes in human colon cancer cell line HCT116, including downregulation of HDAC complex components and cell cycle regulatory machinery, modulation of the AKT/mTOR signaling pathway, and upregulation of FOXO-mediated apoptosis and autophagy related genes. JPS004 can be used in colon cancer-related research.

eALM1137 is a mTOR inhibitor with an IC₅₀ of 4.8 nM. eALM1137 mediates dual inhibition of the mTORC1 and mTORC2 signaling pathways, and inhibits DNA-PK (IC₅₀=77 nM). eALM1137 exhibits antiproliferative and cytostatic activities, and induces G1 cell cycle arrest. eALM1137 is applicable to the research of glioblastoma multiforme.

Torin 2 is an mTOR inhibitor with EC₅₀ of 0.25 nM for inhibiting cellular mTOR activity, and exhibits 800-fold selectivity over PI3K (EC₅₀: 200 nM). Torin 2 also inhibits DNA-PK with an IC₅₀ of 0.5 nM in the cell free assay. Torin 2 can suppress both mTORC1 and mTORC2.

Gedatolisib (PKI-587) is a highly potent dual inhibitor of PI3Kα, PI3Kγ, and mTOR with IC₅₀s of 0.4 nM, 5.4 nM and 1.6 nM, respectively. Gedatolisib is equally effective in both complexes of mTOR, mTORC1 and mTORC2.

Dihydromyricetin is a potent inhibitor with an IC₅₀ of 48 μM on dihydropyrimidinase. Dihydromyricetin can activate autophagy through inhibiting mTOR signaling. Dihydromyricetin suppresses the formation of mTOR complexes (mTORC1/2). Dihydromyricetin is also a potent influenza RNA-dependent RNA polymerase inhibitor with an IC₅₀ of 22 μM.

Omipalisib (GSK2126458) is an orally active and highly selective inhibitor of PI3K with K_is of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM for p110α/β/δ/γ, mTORC1/2, respectively. Omipalisib has anti-cancer activity.

PI-103 is a potent PI3K and mTOR inhibitor with IC₅₀s of 8 nM, 88 nM, 48 nM, 150 nM, 20 nM, and 83 nM for p110α, p110β, p110δ, p110γ, mTORC1, and mTORC2. PI-103 also inhibits DNA-PK with an IC50 of 2 nM. PI-103 induces autophagy.

JR-AB2-011 is a selective mTORC2 inhibitor with an IC₅₀ value of 0.36 μM. JR-AB2-011 inhibits mTORC2 activity by blocking Rictor-mTOR association (K_i: 0.19 μM).JR-AB2-011 decreases the phosphorylation level of Akt, decreases MMP2 activity, thereby reducing the ability of tumor cells to migrate and invade. JR-AB2-011 also induces non-apoptotic cell death.

Vistusertib (AZD2014) is an ATP competitive mTOR inhibitor with an IC₅₀ of 2.81 nM. AZD2014 inhibits both mTORC1 and mTORC2 complexes.

Aloe emodin (Rhabarberone) is a natural hydroxyanthraquinone with antitumor activities. aloe-emodin can bind with mTORC2 and inhibit its kinase activity. Aloe emodin exerts antiproliferation effects and induces cellular apoptosis. Aloe emodin also exhibits antiviral activity that against influenza A virus.

Torkinib (PP 242) is a selective and ATP-competitive mTOR inhibitor with an IC₅₀ of 8 nM. PP242 inhibits both mTORC1 and mTORC2 with IC₅₀s of 30 nM and 58 nM, respectively.

Samotolisib (LY3023414) potently and selectively inhibits class I PI3K isoforms, DNA-PK, and mTORC1/2 with IC₅₀s of 6.07 nM, 77.6 nM, 38 nM, 23.8 nM, 4.24 nM and 165 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, DNA-PK and mTOR, respectively. Samotolisib potently inhibits mTORC1/2 at low nanomolar concentrations.

KU-0063794 is a potent and specific mTOR inhibitor, inhibiting both the mTORC1 and mTORC2 complexes with IC₅₀s of 10 nM.

Apitolisib (GDC-0980; GNE 390; RG 7422) is a selective, potent, orally bioavailable Class I PI3 kinase and mTOR kinase (TORC1/2) inhibitor with IC₅₀s of 5 nM/27 nM/7 nM/14 nM for PI3Kα/PI3Kβ/PI3Kδ/PI3Kγ, and with a?K_i?of 17 nM for mTOR.

CC-115 is a potent and dual DNA-PK and mTOR kinase inhibitor with IC₅₀s of 13 nM and 21 nM, respectively. CC-115 blocks both mTORC1 and mTORC2 signaling.

OSI-027 (ASP7486) is a potent, selective, orally active and ATP-competitive mTOR kinase activity inhibitor with an IC₅₀ of 4 nM. OSI-027 targets both mTORC1 and mTORC2 with IC₅₀s of 22 nM and 65 nM, respectively.