Drug intelligence / Profile preview

desmethylclomipramine

Development stage
Preclinical
Lead developer
Novartis
Modality
Small Molecules
Administration
Oral
01

Overview

Desmethylclomipramine (also known as norclomipramine) is the primary active metabolite of the tricyclic antidepressant clomipramine. While the parent drug clomipramine is a potent serotonin reuptake inhibitor, desmethylclomipramine primarily acts as a potent inhibitor of the norepinephrine transporter (NET). In addition to its psychotropic properties, recent research has highlighted its role as an autophagy inhibitor. In the context of oncology, specifically renal cell carcinoma (RCC), desmethylclomipramine is being investigated for its ability to potentiate the anti-cancer activity of tyrosine kinase inhibitors like sunitinib. By inhibiting autophagy, it helps overcome therapeutic resistance and modulates the p53/p21 signaling pathway to induce cell cycle arrest and apoptosis in cancer cells.

Other names
norclomipramineN-desmethylclomipramine
02

Targets

NET (Norepinephrine Transporter)SERT (Sodium-dependent serotonin transporter)DAT (Dopamine plasma membrane transport protein)

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