E7820 | RBM39 molecular glue

E7820 (289483-69-8) is an angiogenesis inhibitor that suppresses expression of integrins α2, α3, α5, and ß1.¹ Broad-spectrum antitumor and antiangiogenic effects are mainly mediated via integrin α2 suppression.² E7820 has been identified as a molecular glue that induces proteasomal degradation of the U2AF-related splicing factor CAPERα (RBM39) via CRL4^DCAF15 mediated ubiquitination in human cancer cell lines.^3,4  E7820 has also been shown to induce degradation of the aryl hydrocarbon receptor nuclear translator (ARNT), a protein essential in maintaining cellular homeostasis in response to environmental stress.⁵

References/Citations:

1. Funahashi et al. (2002), Sulfonamide derivative, E7820, is a unique angiogenesis inhibitor suppressing an expression of integrin alpha2 subunit on endothelium; Cancer Res. 62 6116
2. Semba et al. (2004), An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a xenograft graft: possible value of integrin alpha2 on platelets as a biological marker; Clin. Cancer Res. 10 1430
3. Uehara et al. (2017), Selective degradation of splicing factor CAPERα by anticancer sulfonamides; Nat. Chem. Biol. 13 675
4. Faust et al. (2020), Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15; Nat. Chem. Biol. 16 7
5. Kim et al. (2020), Aryl Sulfonamides Induce Degradation of Aryl Hydrocarbon Receptor Nuclear Translocator through CRL4^DCAF15 E3 Ligase; Mol. Cells 43 935