mTOR Inhibitor XI, Torin1

Описание:

A cell-permeable pyridinonequinoline derivative that acts as a highly potent, ATP-competitive inhibibitor against mTOR and DNA-PK (IC50 = 4.32 and 6.34 nM, respectively, in cell-free kinase assays), inhibiting class I (IC50 =171, 250, and 564 nM, respectively, against P110γ, P110α/P85α, and P110δ/P85α, respectively), class II (IC50 =176 and 564 nM, respectively, against C2α, and C2β, respectively), and class III (IC50 = 533 nM against hVPS34) PI 3-K only at much higher concentrations. Effectively inhibits mTORC1-mediated S6K1 Thr389 phosphorylation in MEF cultures (IC50 = 2 nM) in vitro, as well as mTORC2-mediated Akt Ser473 and mTORC1-dependent S6 Ser235/236 phosphorylations in murine lung and liver in vivo (up to 6 h after single i.p. dose at 20 mg/kg). Despite its poor in vivo stability (T1/2 = 4.52 h in mice; 10 mg/kg i.p.), Torin1 is reported to completely suppress U87MG-derived tumor expansion in mice when administered via daily i.p. at a high dosage of 200 mg/kg. Also reported to effectively inhibit cellular mTORC1 functionalities known to be rapamycin-resistant (Cat. Nos. 553210, 553211, and 553212M).