mTORC2

Rapamycin complex 2 (mTORC2) functions as a serine/threonine kinase complex that integrates extracellular and intracellular signals to regulate cell survival, metabolism, and cytoskeletal organization^[1]^[2]. Mechanistically, mTORC2 mediates phosphorylation of AGC family kinases including Akt, PKC, and SGK1, influencing cell growth, differentiation, and ion transport^[1]^[3]. Activation of mTORC2 occurs downstream of growth factor receptors and G-protein coupled receptors, and is modulated by stress conditions such as nutrient limitation^[1]^[4]. In disease models, mTORC2 dysregulation contributes to cancer progression, epithelial-mesenchymal transition, and resistance to apoptosis, as observed in colorectal cancer and pheochromocytoma models^[5]^[6]^[7]. Compared with mTORC1, mTORC2 uniquely phosphorylates Akt at Ser473 and SGK1 at Ser422, while being less sensitive to rapamycin inhibition, indicating functional and regulatory specificity^[3]^[8]^[9]. Structural studies reveal that mTORC2 assembly depends on core subunits such as Rictor and SIN1, which determine its localization and substrate specificity^[10]^[11]. For experimental applications, dual mTORC1/2 inhibitors or genetic knockouts targeting Rictor and SIN1 effectively modulate mTORC2-dependent signaling, autophagy, and cell survival in preclinical studies^[6]^[12]^[13]. These insights position mTORC2 as a critical regulatory node for targeted therapeutic interventions and mechanistic studies of cellular growth and stress responses^[1]^[2]^[13].

References:

[1]. Losiewicz MK, et al. mTORC1 and mTORC2 expression in inner retinal neurons and glial cells. Exp Eye Res. 2020 Aug;197:108131.

[2]. Kim LC, et al. mTORC1 and mTORC2 in cancer and the tumor microenvironment. Oncogene. 2017 Apr 20;36(16):2191-2201.

[3]. Ragupathi A, et al. The mTORC2 signaling network: targets and cross-talks. Biochem J. 2024 Jan 25;481(2):45-91.

[4]. Giubellino A, et al. Combined inhibition of mTORC1 and mTORC2 signaling pathways is a promising therapeutic option in inhibiting pheochromocytoma tumor growth: in vitro and in vivo studies in female athymic nude mice. Endocrinology. 2013 Feb;154(2):646-55.

[5]. Zhu J, et al. mTORC1 and mTORC2 Co-Protect against Cadmium-Induced Renal Tubular Epithelial Cell Apoptosis and Acute Kidney Injury by Regulating Protein Kinase B. J Agric Food Chem. 2024 Sep 11;72(36):19667-19679.

[6]. Gulhati P, et al. mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways. Cancer Res. 2011 May 1;71(9):3246-56.

[7]. García-Martínez JM, et al. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J. 2008 Dec 15;416(3):375-85. [Content Brief]

[8]. Oh WJ, et al. mTOR complex 2 signaling and functions. Cell Cycle. 2011 Jul 15;10(14):2305-16.

[9]. Copp J, et al. TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2. Cancer Res. 2009 Mar 1;69(5):1821-7. [Content Brief]

[10]. Stuttfeld E, et al. Architecture of the human mTORC2 core complex. Elife. 2018 Feb 9;7:e33101. [Content Brief]

[11]. Sun Y, et al. mTORC2: a multifaceted regulator of autophagy. Cell Commun Signal. 2023 Jan 5;21(1):4. [Content Brief]

[12]. Thobe K, et al. Unraveling the regulation of mTORC2 using logical modeling. Cell Commun Signal. 2017 Jan 19;15(1):6. [Content Brief]

[13]. Soliman GA, et al. mTOR Ser-2481 autophosphorylation monitors mTORC-specific catalytic activity and clarifies rapamycin mechanism of action. J Biol Chem. 2010 Mar 12;285(11):7866-79. [Content Brief]

[14]. Cardenas-Rodriguez M, et al. The Bardet-Biedl syndrome-related protein CCDC28B modulates mTORC2 function and interacts with SIN1 to control cilia length independently of the mTOR complex. Hum Mol Genet. 2013 Oct 15;22(20):4031-42. [Content Brief]

mTORC2 Related Products (43):

By Type:	Pan (38) Selective (2)
By Effects:	Inhibitors (42) Activator (1)

Cat. No.	Product Name	Effect	Purity

HY-B0795

MHY1485	Activator	99.93%
MHY1485 is a potent cell-permeable mTOR activator that targets the ATP domain of mTOR. MHY1485 inhibits autophagy by suppression of fusion between autophagosomes and lysosomes.

HY-13003

Torin 1	Inhibitor	99.28%
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.

HY-10422

AZD-8055	Inhibitor	99.60%
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.

HY-13328

Sapanisertib	Inhibitor	99.88%
Sapanisertib (INK-128; MLN0128; TAK-228) is an orally available, ATP-dependent mTOR1/2 inhibitor with an IC₅₀ of 1 nM for mTOR kinase.

HY-50673

Dactolisib	Inhibitor	99.94%
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.

HY-183250

eALM1137	Inhibitor
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.

HY-13002

Torin 2	Inhibitor	99.69%
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.

HY-10681

Gedatolisib	Inhibitor	99.89%
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.

HY-N0112

Dihydromyricetin	Inhibitor	99.73%
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.

HY-10297

Omipalisib	Inhibitor	99.94%
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.

HY-10115

PI-103	Inhibitor	99.82%
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.

HY-122022

JR-AB2-011	Inhibitor	98.15%
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.

HY-15247

Vistusertib	Inhibitor	99.70%
Vistusertib (AZD2014) is an ATP competitive mTOR inhibitor with an IC₅₀ of 2.81 nM. AZD2014 inhibits both mTORC1 and mTORC2 complexes.

HY-10474

Torkinib	Inhibitor	99.03%
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.

HY-N0189

Aloe emodin	Inhibitor	98.32%
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.

HY-12513

Samotolisib	Inhibitor	98.85%
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.

HY-13246

Apitolisib	Inhibitor	99.29%
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.

HY-50710

KU-0063794	Inhibitor	99.67%
KU-0063794 is a potent and specific mTOR inhibitor, inhibiting both the mTORC1 and mTORC2 complexes with IC₅₀s of 10 nM.

HY-12868

Bimiralisib	Inhibitor	98.62%
Bimiralisib (PQR309) is a potent, brain-penetrant, orally bioavailable, pan-class I PI3K/mTOR inhibitor with IC₅₀s of 33 nM, 451 nM, 661 nM, 708 nM and 89 nM for PI3Kα, PI3Kδ, PI3Kβ, PI3Kγ and mTOR, respectively. Bimiralisib is an mTORC1 and mTORC2 inhibitor.

HY-16962

CC-115	Inhibitor	99.10%
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.

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