Pomalidomide (19171-19-8) is a thalidomide analog that inhibits cereblon (CRBN), an E3 ubiquitin ligase, IC50 ~3 μM 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
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
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