1222998-36-8 Usage
Description
1-[4-[4-(1-Oxopropyl)-1-piperazinyl]-3-(trifluoromethyl)phenyl]-9-(3-quinolinyl)benzo[h]-1,6-naphthyridin-2(1H)-one, also known as Torin 1, is a potent and selective ATP-competitive mTOR inhibitor with IC50 values of 2 and 10 nM for mTORC1 and mTORC2, respectively. It is a cell-permeable pyridinonequinoline derivative that displays 200-fold selectivity for mTOR over DNA-PK, ATM, and hVps34. Torin 1 is a white solid and has been reported to effectively inhibit mTORC1-mediated S6K1 Thr389 phosphorylation in MEF cultures and mTORC2-mediated Akt Ser473 and mTORC1-dependent S6 Ser235/236 phosphorylations in murine lung and liver in vivo.
Uses
Used in Pharmaceutical Industry:
Torin 1 is used as a potent and selective mTOR inhibitor for the development of therapeutic agents targeting various diseases, including cancer and neurological disorders. Its ability to inhibit mTORC1 and mTORC2 makes it a valuable tool in studying the role of mTOR in these diseases and for the development of targeted therapies.
Used in Research Applications:
Torin 1 is used as a research tool to investigate the role of mTOR in various cellular processes, such as autophagy, cell growth, and cell survival. It has been reported to induce autophagy and alleviate neuronal death in oxidative stress-induced disease models. Additionally, Torin 1 has been used to study the effects of mTOR inhibition on the downregulation of NGF expression in RSC96 cells.
Used in Drug Discovery and Development:
Torin 1 is used in drug discovery and development to identify potential lead compounds and optimize their potency, selectivity, and pharmacokinetic properties. Its ability to inhibit mTORC1 and mTORC2 at low concentrations makes it a valuable starting point for the design of new mTOR inhibitors with improved in vivo stability and efficacy.
Used in Cancer Research:
Torin 1 is used in cancer research to study the role of mTOR in tumor growth, progression, and resistance to conventional therapies. Its potent inhibition of mTORC1 and mTORC2 has been reported to completely suppress U87MG-derived tumor expansion in mice when administered at high dosages, making it a valuable tool for investigating the potential of mTOR inhibition in cancer treatment.
Used in Neurological Research:
Torin 1 is used in neurological research to study the role of mTOR in neurodegenerative diseases and neuronal survival. Its ability to induce autophagy and alleviate neuronal death in oxidative stress-induced disease models has made it a valuable tool for investigating the potential of mTOR inhibition in the treatment of neurological disorders.
Biochem/physiol Actions
Cell permeable: yes
References
References/Citations:
Check Digit Verification of cas no
The CAS Registry Mumber 1222998-36-8 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,2,2,9,9 and 8 respectively; the second part has 2 digits, 3 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 1222998-36:
(9*1)+(8*2)+(7*2)+(6*2)+(5*9)+(4*9)+(3*8)+(2*3)+(1*6)=168
168 % 10 = 8
So 1222998-36-8 is a valid CAS Registry Number.
1222998-36-8Relevant articles and documents
METHOD OF BLOCKING TRANSMISSION OF MALARIAL PARASITE
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Paragraph 0270-0271, (2015/06/03)
The invention provides a method of blocking transmission of a Plasmodium parasite and a method of treating or preventing malaria comprising administering to an animal an effective amount of a first compound of formula I: wherein A, B, R1, R2, R10, and R11 are described herein, either alone or in combination with a second compound selected from elesclomol, NSC 174938, NVP-AUY922, Maduramicin, Narasin, Alvespimycin, Omacetaxine, Thiram, Zinc pyrithione, Phanquinone, Bortezomib, Salinomycin sodium, Monensin sodium, Dipyrithione, Dicyclopentamethylene-thiuram disulfide, YM155, Withaferin A, Adriamycin, Romidepsin, AZD-1 152-HQPA, CAY10581, Plicamycin, CUDC-101, Auranofin, Trametinib, GSK-458, Afatinib, and Panobinostat.
Discovery of 1-(4-(4-Propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9- (quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1 H)-one as a highly potent, selective mammalian target of rapamycin (mTOR) inhibitor for the treatment of cancer
Liu, Qingsong,Chang, Jae Won,Wang, Jinhua,Kang, Seong A.,Thoreen, Carson C.,Markhard, Andrew,Hur, Wooyoung,Zhang, Jianming,Sim, Taebo,Sabatini, David M.,Gray, Nathanael S.
experimental part, p. 7146 - 7155 (2010/12/25)
The mTOR protein is a master regulator of cell growth and proliferation, and inhibitors of its kinase activity have the potential to become new class of anticancer drugs. Starting from quinoline 1, which was identified in a biochemical mTOR assay, we developed a tricyclic benzonaphthyridinone inhibitor 37 (Torin1), which inhibited phosphorylation of mTORC1 and mTORC2 substrates in cells at concentrations of 2 and 10 nM, respectively. Moreover, Torin1 exhibits 1000-fold selectivity for mTOR over PI3K (EC50 = 1800 nM) and exhibits 100-fold binding selectivity relative to 450 other protein kinases. Torin1 was efficacious at a dose of 20 mg/kg in a U87MG xenograft model and demonstrated good pharmacodynamic inhibition of downstream effectors of mTOR in tumor and peripheral tissues. These results demonstrate that Torin1 is a useful probe of mTOR-dependent phenomena and that benzonaphthridinones represent a promising scaffold for the further development of mTOR-specific inhibitors with the potential for clinical utility.
