Development of 2-Aminoadenine-Based Proteolysis-Targeting Chimeras (PROTACs) as Novel Potent Degraders of Monopolar Spindle 1 and Aurora Kinases.

Monopolar spindle 1 (Mps1, also known as TTK) and Aurora kinase (AURK) A and B are critical regulators of mitosis and have been linked to the progression of various cancers. Here, we report the design, synthesis, and biological evaluation of a series of PROTACs (proteolysis-targeting chimeras) targeting TTK and AURKs. We synthesized various degrader molecules based on four different 2-aminoadenine-based ligands, recruiting either cereblon or VHL as the E3-ligase.

Synthesis and antiproliferative activities of steroidal lactam conjugates bearing a new nitrogen mustard.

Alkylating agents are potent anticancer compounds that exert their anticancer properties through the inhibition of cell replication and transcription leading to cell death. Despite the numerous benefits, these agents also have serious drawbacks such as their high toxicity and low specificity towards cancer cells. As previously reported by our group, conjugation of alkylating agents with azasteroids can reduce their systemic toxicity and enhance their anticancer activity.

Recent Advances in Natural Product-Based Hybrids as Anti-Cancer Agents.

Cancer is one of the top leading causes of death worldwide. It is a heterogenous disease characterized by unregulated cell proliferation and invasiveness of abnormal cells. For the treatment of cancer, natural products have been widely used as a source of therapeutic ingredients since ancient times.

Discovery of steroidal lactam conjugates of POPAM-NH with potent anticancer activity.

Steroidal prodrugs of nitrogen mustards such as estramustine and prednimustine have proven effective anticancer agents in clinical use since the 1970s. In this work, we aimed to develop steroidal prodrugs of the novel nitrogen mustard POPAM-NH. POPAM-NH is a melphalan analogue that was coupled with three different steroidal lactams.