Mechanistic Target of Rapamycin Complex 1

An evolutionarily conserved multiprotein complex that functions as a cellular energy sensor and regulator of protein synthesis for cell growth and proliferation. It consists of TOR SERINE-THREONINE KINASES; REGULATORY-ASSOCIATED PROTEIN OF MTOR (RAPTOR); MLST8 PROTEIN; and AKT1 substrate 1 protein. The activity of the complex is regulated by SIROLIMUS; INSULIN; GROWTH FACTORS; PHOSPHATIDIC ACIDS; some amino acids or amino acid derivatives, and OXIDATIVE STRESS.

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Networked: 3687 relevant articles (174 outcomes, 412 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Sabatini, David M: 32 articles (01/2021 - 01/2006)
2.	Bai, Xiaochun: 31 articles (09/2021 - 08/2012)
3.	Kwiatkowski, David J: 29 articles (01/2022 - 05/2008)
4.	Manning, Brendan D: 29 articles (01/2022 - 10/2006)
5.	Henske, Elizabeth P: 28 articles (01/2022 - 01/2012)
6.	Hall, Michael N: 26 articles (11/2021 - 02/2006)
7.	Rüegg, Markus A: 23 articles (01/2020 - 03/2011)
8.	Proud, Christopher G: 20 articles (05/2021 - 06/2007)
9.	Kasinath, Balakuntalam S: 19 articles (10/2021 - 02/2008)
10.	Blenis, John: 19 articles (01/2021 - 02/2009)

Related Diseases

1.	Neoplasms (Cancer) 11/01/2021 - "In contrast, simultaneous inhibition of MALT1 and MTORC1 prevented S6 phosphorylation, yielded potent activity against DLBCL cell lines and primary patient specimens, and resulted in more profound tumor regression and significantly improved survival of ABC-DLBCLs in vivo compared with PI3K inhibitors. " 01/01/2011 - "These findings indicate that the combined inhibition of mTORC1 and MNK may prove beneficial in the treatment of CTCL and other malignancies." 12/08/2020 - "In conclusion, hyperactive mutation of PI3K-AKT-mTOR signaling protects cancer cells from oxidative stress and ferroptotic death through SREBP1/SCD1-mediated lipogenesis, and combination of mTORC1 inhibition with ferroptosis induction shows therapeutic promise in preclinical models." 01/01/2019 - "Finally, we also review the therapeutic efficacy of mTORC1 inhibitors in cancer treatments, considering its use in combination with other drugs, with particular focus on cellular metabolism inhibitors, that could help improve their anti neoplastic effect and eliminate cancer cells in patients." 09/01/2011 - "However, mTORC1 is frequently activated in ccRCC, and mTORC1 inhibitors are effective against this tumor type; a paradox herein examined. "
2.	Breast Neoplasms (Breast Cancer) 01/01/2021 - "SIGNIFICANCE: These findings show that genetic lesions of multiple negative regulators of mTORC1 could limit the efficacy of PI3Kα inhibitors in breast cancer, which may guide patient selection strategies for future clinical trials." 01/01/2023 - "Interestingly, we found that exosomal miR-148b-3p could induce M2 macrophage polarization via the TSC2/mTORC1 signaling pathway in breast cancer. " 01/01/2023 - "PCK2 also regulates nutrient status-dependent mTORC1 pathway activation in ER+ breast cancer. " 01/01/2023 - "PEPCK-M promotes proliferation and cell cycle progression in ER+ breast cancer via upregulation of the mTORC1 and E2F1 pathways. " 01/01/2023 - "PEPCK-M promoted the activation of mTORC1 downstream signaling molecules and the E2F1 pathways in ER+ breast cancer. "
3.	Inflammation (Inflammations) 01/01/2023 - "Overall, RIPK1/mTORC1 signalling suppression improved HG-induced apoptosis, inflammation and oxidative stress through activation autophagy. " 03/01/2020 - "The selective RNA interference-mediated and pharmacological inhibition of mTOR complex 1 (mTORC1) was protective against inflammation-induced disc cellular apoptosis, senescence, and extracellular matrix catabolism, through the induction of autophagy and the activation of the Akt-signaling network. " 12/01/2022 - "In the present study, we found that the abnormal bone metabolism of RA is related to the activation of the mechanistic targets of mTORC1 pathway, and chronic inflammation which regulates the differentiation of preosteoblast through mitophagy. " 01/01/2017 - "In conclusion, our present study demonstrates that endothelial mTORC1 deletion protects against hindlimb ischemic injury in diabetic mice possibly via activation of autophagy, attenuation of oxidative stress and alleviation of inflammation. " 12/01/2023 - "RSDS-upregulated genes in macrophages, monocytes, and granulocytes significantly enriched immunometabolic pathways thought to play a role in myeloid-driven inflammation (glycolysis, HIF-1 signaling, MTORC1 signaling) as well as pathways related to oxidative phosphorylation (OXPHOS) and oxidative stress (p < 0.05 and FDR<0.1). "
4.	Fibrosis (Cirrhosis) 12/18/2021 - "Therapeutic interventions targeting IS and mTORC1 could be effective against renal fibrosis in CKD." 01/01/2020 - "Constitutive activation of mTORC1 in RPTCs induces renal fibrosis and failure and abolishes the renal-protective effects of SGLT2i in diabetes. " 11/01/2020 - "These findings suggest exercise modulates the AMPK/mTORC1 pathway in patients with NASH and may guide the design of future studies into the mechanism of how exercise improves NASH and possibly reverses fibrosis." 01/01/2020 - "As a result, we have presented the first study on the role of TRIM6 in the mTORC1 pathway in renal fibrosis models and our findings suggested that TRIM6 may be a potential target for the treatment of renal fibrosis." 11/01/2023 - "Inhibition of the mTORC1 pathway alleviates adipose tissue fibrosis."
5.	Insulin Resistance 03/01/2015 - "Insulin resistance induced by a brief HFD was not attributable to greater activation of the mTORC1 or the IKK/NF-κB pathway in muscle, and exercise-induced improvement in insulin sensitivity was not attributable to attenuated activation of these pathways in muscle. " 10/01/2022 - "Discoveries of PHLPP1-mediated insulin resistance and pancreatic β cell death via the PHLPP1/2-Mst1-mTORC1 triangular loop have shed light on its significance in diabetology. " 01/01/2020 - "DOCK5 regulates energy balance and hepatic insulin sensitivity by targeting mTORC1 signaling." 01/01/2019 - "In the context of insulin resistance, AKT signaling is affected resulting in sustained activation of mTORC1 and enhanced glycolysis. " 01/01/2017 - "This further suppression of mTORC1 activity protected cells from Aβ-induced toxicity and insulin resistance. "

Related Drugs and Biologics

1.	Sirolimus (Rapamycin)
2.	Mechanistic Target of Rapamycin Complex 1
3.	Mechanistic Target of Rapamycin Complex 2
4.	TOR Serine-Threonine Kinases
5.	Phosphotransferases (Kinase)
6.	Everolimus
7.	Proteins (Proteins, Gene)
8.	Mitogen-Activated Protein Kinase Kinases (MEKs)
9.	MTOR Inhibitors
10.	Sirtuin 1

Related Therapies and Procedures

1.	Therapeutics
2.	Castration
3.	Neoadjuvant Therapy
4.	Protein-Restricted Diet (Diet, Protein Restricted)
5.	Oral Administration