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4-(Difluoromethyl)-5-(4-((3R,5S)-3,5-dimethylmorpholino)-6-((R)-3-methylmorpholino)-1,3,5-triazin-2-yl)pyridin-2-amine (PQR626), a Potent, Orally Available, and Brain-Penetrant mTOR Inhibitor for the Treatment of Neurological Disorders.
Borsari C, Keles E, Rageot D, Treyer A, Bohnacker T, Bissegger L, De Pascale M, Melone A, Sriramaratnam R, Beaufils F, Hamburger M, Hebeisen P, Löscher W, Fabbro D, Hillmann P, Wymann MP. Borsari C, et al. Among authors: loscher w. J Med Chem. 2020 Nov 25;63(22):13595-13617. doi: 10.1021/acs.jmedchem.0c00620. Epub 2020 Nov 9. J Med Chem. 2020. PMID: 33166139 Free article.
The novel, catalytic mTORC1/2 inhibitor PQR620 and the PI3K/mTORC1/2 inhibitor PQR530 effectively cross the blood-brain barrier and increase seizure threshold in a mouse model of chronic epilepsy.
Brandt C, Hillmann P, Noack A, Römermann K, Öhler LA, Rageot D, Beaufils F, Melone A, Sele AM, Wymann MP, Fabbro D, Löscher W. Brandt C, et al. Among authors: loscher w. Neuropharmacology. 2018 Sep 15;140:107-120. doi: 10.1016/j.neuropharm.2018.08.002. Epub 2018 Aug 3. Neuropharmacology. 2018. PMID: 30081001
Discovery and Preclinical Characterization of 5-[4,6-Bis({3-oxa-8-azabicyclo[3.2.1]octan-8-yl})-1,3,5-triazin-2-yl]-4-(difluoromethyl)pyridin-2-amine (PQR620), a Highly Potent and Selective mTORC1/2 Inhibitor for Cancer and Neurological Disorders.
Rageot D, Bohnacker T, Melone A, Langlois JB, Borsari C, Hillmann P, Sele AM, Beaufils F, Zvelebil M, Hebeisen P, Löscher W, Burke J, Fabbro D, Wymann MP. Rageot D, et al. Among authors: loscher w. J Med Chem. 2018 Nov 21;61(22):10084-10105. doi: 10.1021/acs.jmedchem.8b01262. Epub 2018 Nov 14. J Med Chem. 2018. PMID: 30359003 Free article.
Novel brain permeant mTORC1/2 inhibitors are as efficacious as rapamycin or everolimus in mouse models of acquired partial epilepsy and tuberous sclerosis complex.
Theilmann W, Gericke B, Schidlitzki A, Muneeb Anjum SM, Borsdorf S, Harries T, Roberds SL, Aguiar DJ, Brunner D, Leiser SC, Song D, Fabbro D, Hillmann P, Wymann MP, Löscher W. Theilmann W, et al. Among authors: loscher w. Neuropharmacology. 2020 Dec 1;180:108297. doi: 10.1016/j.neuropharm.2020.108297. Epub 2020 Sep 3. Neuropharmacology. 2020. PMID: 32890589
878 results