PP242 | Dual mTORC1/mTORC2 inhibitor

PP242 (1092351-67-1) is an ATP-competitive mTORC1/mTORC2 inhibitor (IC₅₀ = 8 nM) displaying high selectivity over PI 3K family kinases (IC₅₀s =0.102 to 2.2 μM) and modest selectivity over PKC family kinases (IC₅₀s =0.049 to 0.198  μM).^1,2 PP 242 (but not rapamycin) induced the death of mouse and human leukemia cells but was much weaker than rapamycin at induction of death of normal lymphocytes.³ Restores lysosomal activity and facilitates clearance of amyloid-β in a mouse model of dry age-related macular degeneration.⁴ Inhibits glioblastoma cell proliferation, migration, invasiveness, and stemness.⁵

References/Citations:

1. Aspel et al. (2008), Targeted polypharmacology: Discovery of dual inhibitors of tyrosine and phosphoinositide kinases; Nat. Chem. Biol. 4 691
2. Feldman et al. (2009), Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2; PLoS Biol. 7 371
3. Janes et al. (2010), Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor; Nat. Med. 16 205
4. Jo et al. (2023), Activation of Lysosomal Function Ameliorates Amyloid-ß-Induced Tight Junction Disruption in the Retinal Pigment Epithelium; Mol. Cells 46 675
5. Mecca et al. (2018), PP242 Counteracts Glioblastoma Cell Proliferation, Migration, Invasiveness and Stemness Properties by Inhibiting mTORC2/AKT; Front. Cell. Neurosci. 12 99