CC-90009
Cereblon modulator/Molecular glue / CC-90009 is a modulator of the cullin ring ligase 4-cereblon E3 ubiquitin ligase complex that specifically targets GSPT1 (G1 to S phase transition 1; EC50 = 9 nM; also known as eRF3a) instead of Ikaros (IKZF1) and Aiolos (IKZF3).1 It rapidly induced apoptosis and reduced leukemia engraftment and leukemia stem cells across a wide spectrum of acute myeloid leukemia xenograft patient samples including refractory/relapsed cases.2 The anti-AML activity of CC-90009 was shown to be regulated by multiple signaling pathways including the ILF/ILF3 complex, mTOR, and the integrated stress response. CC-90009 was able to potentiate premature termination codon (PTC; 11% of all genetic lesions in patients with inherited diseases contain this type of mutation) readthrough by aminoglycosides via degradation of eukaryotic release factors 1 (eRF1) and 3 (eRF3a/b) in various heritable disease models.3 It was also able to enhance aminoglycoside PTC readthrough of the mutated retinoblastoma (RB1) gene in MDA-MB-436 breast carcinoma cells and SW1783 astrocytoma cells.4
Biochemicals & reagents
1860875-51-9
Eragidomide
1) Hansen et al. (2021), CC-90009: A Cereblon E3 Ligase Modulating Drug That Promotes Selective Degradation of GSPT1 for the Treatment of Acute Myeloid Leukemia; J. Med. Chem. 64 1835 2) Surka et al. (2021), CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells; Blood 137 661 3) Baradaran et al. (2021), Effect of small molecule eRF3 degraders on premature termination codon readthrough; Nucleic Acids Res. 49 3692 4) Palomar-Siles et al. (2023), Pharmacological induction of translational readthrough of nonsense mutations in the retinoblastoma (RB1) gene; PLoS One 18 e0292468
-20°C
TARGET: Ubiquitin ligase; Molecular glue -- PATHWAY: Degradation; Posttranslational modification; mTOR; Protein synthesis -- RESEARCH AREA: Ubiquitin/Proteasome; Cancer stem cells; Immunology -- DISEASE AREA: Cancer