AZD8055 CAS NO.1009298-09-2

azd8055 is a novel atp-competitive mtor inhibitor with ic50 of 0.8 nm with excellent selectivity (～1,000-fold) against pi3k isoforms and atm/dna-pk.
ic50 value: 0.8 nm [1]
target: mtor
in vitro: azd8055 shows low activity (～1,000-fold) against all pi3k isoforms (α, β, γ, δ) and other members of the pi3k-like kinase family (atm and dna-pk). azd8055 inhibits the phosphorylation of mtorc1 (p70s6k and 4e-bp1) as well as phosphorylation of the mtorc2 (akt) and downstream proteins. the rapamycin-resistant t37/46 phosphorylation sites on 4e-bp1 can be fully inhibited by azd8055, resulting in significant inhibition of cap-dependent translation. azd8055 potently inhibits proliferation in u87mg, a549 and h838 cells with ic50 of 53, 50 and 20 nm, respectively. azd8055 also induces autophagy and increased lc3-ii levels in h838 and a549 cells [1]. azd8055 decreases aml blast cell proliferation and cell cycle progression, reduces the clonogenic growth of leukemic progenitors and induces caspase-dependent apoptosis in leukemic cells but not in normal immature cd34+ cells [2].
in vivo: azd8055 inhibits the ps6 and pakt in u87mg and a549 xenografts at 2.5/10 mg/kg, which leads to tumor growth inhibition. azd8055 shows significant antitumor activity in many xenografts, including u87mg, bt474c, a549, calu-3, lovo, sw620, pc3 and mes-sa at a dose of 10/20 mg/kg [1]. azd8055 induces ~40% reduction in tumour volume, accompanied by ablation of phosphorylation of akt, s6k and sgk protein kinases. administration of azd8055 (5mg/kg, bid) and saha (100 mg/kg/d) results in complete tumor growth inhibition in pten+/lkb1+/hypo xenografts without side effects on mice by inhibition of mtorc1 and mtorc2 signaling [3].