AZD8055 is an investigational drug, classified as a mammalian target of rapamycin (mTOR) inhibitor. It is currently undergoing research and development, primarily within preclinical and early-phase clinical trials, and is not yet available for widespread medical use. Its development has focused on potential therapeutic applications, particularly in oncology.
How AZD8055 Works
The mammalian target of rapamycin (mTOR) is a protein kinase that plays a central role in regulating cell growth, division, and survival. It forms two distinct complexes, mTORC1 and mTORC2. mTORC1 is sensitive to rapamycin, an older mTOR inhibitor, while mTORC2 is generally resistant.
AZD8055 functions as an ATP-competitive inhibitor, interfering with the energy mTOR kinase needs. Unlike rapamycin, AZD8055 inhibits both mTORC1 and mTORC2 complexes. This dual inhibition prevents the activation of downstream targets, disrupting abnormal cell growth and proliferation.
Diseases Under Investigation for AZD8055
AZD8055 has been investigated for its potential in treating various types of cancer. It has shown promise in preclinical models and early clinical trials, demonstrating anti-tumor activity across a range of human tumor types in xenograft models (studies conducted in mice using human cancer cells).
Specific cancers where AZD8055 has been studied include solid tumors and lymphomas. In mouse models, it has shown dose-dependent tumor growth inhibition in human glioma xenografts. Studies in non-small cell lung cancer (NSCLC) and glioblastoma cell lines have also shown potent inhibition of proliferation.
Further research indicates its activity against acute myeloid leukemia (AML) cells, where it blocked both mTORC1 and mTORC2 signaling, leading to decreased AML blast cell proliferation and induced apoptosis. AZD8055 has also been studied in human cervical cancer cell lines, demonstrating inhibition of proliferation and glycolysis, and induction of apoptosis. Its use is still experimental, and further clinical investigation is needed.
Potential Side Effects
In a phase I study involving patients with advanced solid malignancies and lymphomas, the maximum tolerated dose was 90 mg twice daily. Dose-limiting toxicities, which are adverse events severe enough to limit the amount of drug that can be given, included grade 3 increases in transaminases. These liver enzyme elevations were generally reversible.
Common adverse events reported included increased alanine aminotransferase, increased aspartate aminotransferase, and fatigue. While toxicities often associated with older mTOR inhibitors, such as rash and mucositis, were not dose-limiting with AZD8055, elevated transaminases occurred across most dose levels.
Current Development Status
AZD8055 has progressed through preclinical research and into early-phase clinical trials. It has been described as a “first-in-class” dual inhibitor of mTORC1 and mTORC2, distinguishing it from older mTOR inhibitors like rapamycin. Clinical trials primarily focused on Phase I studies, which aim to assess the drug’s safety, tolerability, pharmacokinetics (how the body handles the drug), and preliminary anti-tumor activity in patients with advanced solid tumors and lymphomas.
While some studies have been completed, the global highest research and development status for AZD8055 is currently listed as “Discontinued.” This indicates that while preclinical data showed promising anti-tumor activity and it entered early human trials, further development may have been halted or paused. The use of AZD8055 for research purposes is suitable for in vitro and ex vivo studies only.