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Updated: Jun 19, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Palliative oncology: thalidomide
1Division of Hematology and Oncology, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA. prommer.eric@mayo.edu
Abstract:
After decades of disuse because of its teratogenic effects, thalidomide has had a resurgence of use as a promising therapeutic agent for multiple myeloma. Its mechanism of action involves activation of the immune system, antiangiogenic effects, and inhibition of cytokines. Thalidomide does not interact with the cytochrome oxidase system. It is not significantly metabolized, but it does undergo nonenzymatic hydrolysis in plasma. The resulting products are inactive. Despite the potential adverse effects of peripheral neuropathy, constipation, deep vein thrombosis, somnolence, rash, and orthostatic hypotension, thalidomide is an effective first-line agent for multiple myeloma in combination with dexamethasone or melphalan and prednisone. It has also been studied in the palliative care of patients with cytokine-based syndromes such as anorexia-cachexia syndrome. This review describes its use in oncology, hematology, and palliative care.
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