914913-88-5

Palomid 529 is a novel non-steroidal small molecule inhibitor

Palomid 529 (P529) inhibits the mTORC1 and mTORC2 complexes and reduces the phosphorylation of pAktS473, pGSK3βS9 and pS6, but has no effect on pMAPK and pAktT308. Phase 1.

This novel Akt inhibitor (FW = 406.43 g/mol; CAS 914913-88-5; Solubility: 80 mg/mL DMSO; <1 mg/mL H2O or Ethanol; Abbreviation: P529), also named 8- (1-hydroxyethyl) -2-methoxy-3- (4-methoxybenzyloxy) benzo[c]chromen-6-one, inhibits tumor angiogenesis, vascular permeability, and tumour growth. P529 has the additional benefit of blocking pAktS473 signaling consistent with blocking TORC2 in all cells and thus bypassing feedback loops that lead to increased Akt signaling in some tumor cells. P529 significantly enhance the antiproliferative effect of radiation in prostate cancer PC-3 cells. Analysis of signal transduction pathways targeted by P529 exhibited a decrease in p-Akt, VEGF, MMP-2, MMP-9, and Id-1 levels after radiation treatment. Palomid 529 is an effective suppressor of Müller cell proliferation, glial scar formation, and photoreceptor cell death in a rabbit model of retinal detachment, or RD. Palomid 529 significantly suppresses breast cancer susceptibility gene (Brca1) -deficient tumor growth in mice through inhibition of both Akt and mTOR signaling.

mTORC1