Spain-based Iteria Biopharma has registered a first-in-human Phase I/Ib trial of ITR-251 in advanced solid tumors, with a prostate cancer expansion that will explore combining MAO-A inhibition with hormonal treatment after disease progression. The study is not yet recruiting, with an estimated start in Q4 2026.
Iteria identifies ITR-251 as an inhibitor of monoamine oxidase A (MAO-A), an enzyme best known for breaking down neurotransmitters. Its oncology rationale comes from research linking MAO-A to androgen receptor signaling and resistance to hormonal therapies in prostate cancer.
A study published in Nature Communications found that inhibiting MAO-A with phenelzine or clorgyline restored sensitivity to enzalutamide in resistant prostate cancer models, including cell and animal experiments. Separate research in Cancer Research identified a mutually reinforcing relationship between MAO-A and androgen receptor activity, and found that targeting MAO-A enhanced the growth-inhibitory effects of several androgen receptor inhibitors in cancer cells.
MAO inhibition has previously been explored clinically in prostate cancer. The antidepressant phenelzine previously underwent a small Phase II study that reported PSA reductions in some patients but also cardiovascular toxicities. According to Spain’s research funding agency, Iteria’s ONCOMAO project is developing selective, noncovalent MAO-A inhibitors with limited brain penetration, with ITR-251 described as having these intended characteristics. This offers a potential route to differentiate the drug from older inhibitors, although clinical advantages have yet to be established.