U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

Showing 9401 - 9410 of 132111 results

Status:
Other

Class (Stereo):
CHEMICAL (ACHIRAL)

Status:
Other

Class (Stereo):
CHEMICAL (ACHIRAL)

Torin 1 is a highly potent and selective ATP-competitive mTOR inhibitor discovered as a potential anticancer drug. It directly inhibits two functionally distinct complexes, mTORC1 and mTORC2, that coordinately promote cell growth, proliferation, and survival and impairs cell growth and proliferation to a far greater degree than rapamycin. Torin 1 is a picomolar inhibitor of mTORC1 enzymatic activity and single digit nanomolar inhibitor of cellular mTOR activity and has more than 800-fold selectivity between mTOR and PI3K. The pharmacokinetic properties of torin 1 were both in vitro and in vivo. It exhibited a short in vivo half-life and low oral bioavailability but displayed pharmacodynamic inhibition of both mTORC1 and mTORC2 outputs in lung and liver. Torin 1 dosed once a day at 20 mg/kg for 10 days demonstrated efficacy in a U87MG glioblastoma xenograft mouse model. Torin1 also caused lipin 1 nuclear translocation suggesting that lipin 1 cytoplasmic-nuclear relocalization responds to mTORC1 and not mTORC2 status. Torin 1 completely inhibited S106 lipin 1 phosphorylation and impaired S237 and S472 lipin 1 phosphorylation at prolonged exposure. Inhibition of mTORC1 in the liver significantly impairs SREBP function and makes mice resistant, in a lipin 1-dependent fashion, to the hepatic steatosis and hypercholesterolemia induced by a high fat and cholesterol diet. However, if potent mTORC1 inhibiting could be useful as potential treatments for metabolic syndrome has to be elucidated yet.

Showing 9401 - 9410 of 132111 results