Pomalidomide
Cereblon ubiquitination inhibitor / Thalidomide analog. Inhibits cereblon (CRBN) an E3 ubiquitin ligase, IC50 ~3 uM for CRBN-DDB1 complex.1 Displays antiangiogenic and immunomodulatory activity in vivo potently inhibiting the production of TNFα and IL-2.2 Promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome.3 Conjugation with other ligands is a strategy to target proteins for in vivo proteasomal degradation via PROTACS.4,5
Biochemicals & reagents
19171-19-8
3-amino-N-(2,6-dioxo-3-piperidyl)phthalamide
1) Lopez-Girona et al. (2012), Cereblon is direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide; Leukemia, 26 2326 2) Zhu et al. (2013), Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma; Leukemia Lymphoma, 54 683 3) Donovan et al. (2018), Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome; Elife, 7 e38430 4) Winter et al. (2015), DRUG DEVELOPMENT. Phthalimide conjunction as a strategy for in vivo target protein degradation; Science, 348 1376 5) Lohbeck and Miller (2016), Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development; Bioorg. Med. Chem. Lett., 26 5260
-20°C
TARGET: Ubiquitin ligase; Molecular glue -- PATHWAY: Degradation; Cytokine -- RESEARCH AREA: Immunology; Angiogenesis; Ubiquitin/Proteasome -- DISEASE AREA: Inflammation; Cancer