Akt-Targeted Library

ChemDiv’s library of Akt-targeting inhibitors contains 15,000 compounds.

AKT kinases, also known as protein kinase B (PKB), are a family of serine/threonine-specific protein kinases that play a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. There are three isoforms of AKT in humans: AKT1, AKT2, and AKT3, each with unique and overlapping functions within the cell.  The first member is deeply involved in cellular survival pathways by inhibiting apoptotic processes. It is also able to induce protein synthesis pathways and is therefore a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy, and general tissue growth. Since it can block apoptosis, and thereby promote cell survival, Akt1 has been implicated as a major factor in many types of cancer. Akt1 was originally identified as the oncogene in the transforming retrovirus AKT8. The second isoform, Akt2, is an important signaling molecule in the Insulin signaling pathway. It is required to induce glucose transport. The role of Akt3 is less clear, though it appears to be predominantly expressed in brain. Akt is associated with tumor cell survival, proliferation, and invasiveness.

These kinases are integral to the PI3K/AKT/mTOR signaling pathway, which is critical for cell survival and growth. Dysregulation of AKT activity has been found in a variety of diseases, most often cancer, because of its role in regulating cell survival and proliferation, which can lead to tumor growth and resistance to chemotherapy.

In drug discovery, AKT kinases have become significant targets because of their central role in many pathways that are frequently altered in cancer. Inhibitors targeting AKT are being developed as potential therapeutic agents, especially for cancers where the PI3K/AKT/mTOR pathway is abnormally activated. These inhibitors aim to suppress tumor growth and enhance the efficacy of other therapeutic strategies. The challenge in developing AKT kinase inhibitors lies in achieving selective targeting to minimize off-target effects, which is critical for the successful treatment of cancer with minimal side effects. As research progresses, AKT inhibitors continue to show promise in preclinical and clinical settings, offering hope for new, effective cancer treatments.

ChemDiv's library of selective inhibitors for Akt kinases is an extended collection designed using advanced machine learning techniques. It utilizes ligand-based methodologies to provide a high level of selectivity in identified potential Akt kinase inhibitors. The compounds in this library were selected for their diversity, focusing on varied Murcko scaffolds, a method that identifies the core structure in complex molecules. This approach ensures a wide range of structural variations, enhancing the likelihood of identifying novel and effective inhibitors. With a focus on Akt kinases, this library serves as a valuable resource in drug discovery research. Researchers can explore this collection to find potential therapeutic agents, especially for conditions where the PI3K/AKT/mTOR pathway is dysregulated. The use of ML in the library's creation not only speeds up the discovery process but also increases the precision of targeting Akt kinases, promising more effective and safer treatments for various diseases.