What is the Origin of Steroidal AI?

The concept of Aromatase Inhibitors (AIs) arose from the need to suppress estrogen production in hormone-sensitive cancers. Steroidal AIs, such as exemestane, were developed to provide a more potent and lasting inhibition compared to earlier, reversible non-steroidal compounds. The term 'Steroidal' denotes the presence of the steroid nucleus in their chemical structure, which allows them to be recognized as a substrate mimic by the aromatase enzyme, leading to their unique, irreversible inhibitory mechanism.

What is the Mechanism of Steroidal AI?

The mechanism is characterized by irreversible inactivation. The steroidal inhibitor enters the active site of the aromatase enzyme, where it is processed similarly to the natural androgen substrate. During this catalytic process, a reactive intermediate is generated which then forms a stable, covalent bond with a critical amino acid residue within the enzyme's active site. This permanent binding renders the enzyme permanently inactive, requiring the body to synthesize new aromatase enzyme molecules to restore estrogen production, leading to a sustained suppression of estrogen levels.

Steroidal AI

Meaning

Steroidal AI refers to a class of pharmaceutical agents known as Steroidal Aromatase Inhibitors, which are structurally similar to the natural steroid substrates of the aromatase enzyme. These molecules function as mechanism-based, or suicidal, inhibitors, meaning they irreversibly bind to the aromatase enzyme, forming a permanent covalent bond that inactivates the enzyme. This class of drug is used to effectively reduce estrogen levels by permanently blocking the conversion of androgens into estrogens, providing a robust and sustained estrogen suppression effect.