AZD8055, Free Base (CCG-168, CAS 1009298-09-2), >99%

LC Laboratories' Product Number A-2345 - AZD8055, Free Base (CCG-168, CAS 1009298-09-2), >99% - for research use only. AZD8055 is a novel ATP-competitive and selective inhibitor of mammalian target of rapamycin (mTOR) kinase with an IC50 value of 0.8 nM. It inhibits the phosphorylation of mTORC1 substrates p70S6K and 4E-BP1, mTORC2 substrate AKT, and downstream proteins. AZD8055 fully inhibits the rapamycin-resistant T37/46 phosphorylation sites on 4E-BP1 and results in significant inhibition of cap-dependent translation. AZD8055 potently inhibits proliferation and induces autophagy in vitro, and causes significant growth inhibition and/or regression in xenografts in vivo. The combination of the MAPK extracellular signal-regulated kinase (MEK1/2) inhibitor selumetinib (AZD6244, please see Cat. No. S-4490, Selumetinib, Free Base) with the dual mTORC1 and mTORC2 inhibitor AZD8055 were used in nude mouse xenograft models of human lung adenocarcinoma (non-small cell lung cancers) and colorectal carcinoma. The treatment was well tolerated and showed improved antitumor efficacy when compared to the respective monotherapies. The reciprocal pathway inhibition from the combination group was associated with increased apoptosis and Bcl-2 interacting mediator of cell death (Bim) expression in tumor tissue. The mTOR molecular signaling pathway plays a critical role in cerebral vasospasm following subarachnoid hemorrhage (SAH). AZD8055 significantly inhibited the level and expression of key mTOR signaling pathway molecules including mTOR, P70S6K1, 4E-BP1 and PCNA, and thus inhibited the mTOR pathway, thus suggesting that AZD8055 has the potential to treat vasospasm following SAH. AZD8055 inhibited both mTORC1 and mTORC2 signaling in acute myeloid leukemia (AML) in mice. AZD8055 significantly reduced the tumor growth and markedly increased the survival of AML transplanted mice without apparent toxicity. AZD8055 blocked the chemotherapy-induced cell death promoted by ectopic wild-type p62. The combination of mTOR kinase inhibitor AZD8055 and histone deacetylase inhibitor SAHA (vorinostat, please see Cat. No. V-8477, Vorinostat) almost completely inhibited tumor growth of hepatocellular carcinoma (HCC) by upregulating Bim and abrogating AKT. However, either agent alone demonstrated only 30% inhibition in primary HCC xenografts.Safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8055 in advanced solid tumors were tested in Western patients and Japanese patients. The maximum tolerated dose for AZD8055 was 90 mg BID. Aside from elevated transaminases, the drug had an acceptable toxicity profile.Related CAS numbers: 1201799-05-4 for the fumarate salt form of AZD8055.

• Supplier: LC Laboratories
• Product #: A-2345
• Sku #: A-2345_5mg