Jun 22, 2016 · Immunomodulatory drugs bind to cereblon (CRBN) to confer differentiated substrate specificity on the CRL4 CRBN E3 ubiquitin ligase. Here we report the identification of a new cereblon...

Oct 16, 2020 · Molecular docking studies with CRBN and GSPT1 followed by analogue synthesis identified a possible hydrogen bond interaction with the central pyrimidine ring as a molecular determinant of hit compounds' selectivity.

Molecular docking studies with CRBN and GSPT1 followed by analog synthesis identified a possible hydrogen bond interaction with the central pyrimidine ring as a molecular determinant of hit compounds’ selectivity.

Jan 26, 2023 · Here, we profile 14 closely-related thalidomide derivatives in CRBN occupancy, and IKZF1 and GSPT1 degradation cell-based assays, and use crystal structures, computational docking and molecular dynamics to delineate subtle structure–activity relationships.

Jul 14, 2016 · Immunomodulatory drugs bind to cereblon (CRBN) to confer differentiated substrate specificity on the CRL4(CRBN) E3 ubiquitin ligase. Here we report the identification of a new cereblon modulator, CC-885, with potent anti-tumour activity.

Aug 8, 2024 · CC-885, a thalidomide derivative, is an immunomodulatory drug that binds to cereblon (CRBN) and leads to GSPT1 degradation [9]. CRBN is a substrate-receptor component of the E3...

Aug 20, 2021 · The representative double-mechanism degrader, GBD-9, efficiently degraded BTK and GSPT1 by recruiting the E3 ligase cereblon (CRBN) in various DLBCL and AML cell lines.

Jan 30, 2016 · The anti-tumour activity of CC-885 is mediated through the cereblon-dependent ubiquitination and degradation of the translation termination factor GSPT1. Patient-derived acute myeloid leukaemia tumour cells exhibit high sensitivity to CC-885, indicating the clinical potential of this mechanism.

Jul 5, 2024 · AN5777 binds recombinant CRBN and induces GSPT1 degradation through the UPS. The proliferation inhibition of AN5777 depends on CRBN and GSPT1. AN5777 dose-dependently induces G1 phase arrest and apoptosis.

Mar 30, 2017 · We previously disclosed the identification of cereblon modulator 3 (CC-885), with potent antitumor activity mediated through the degradation of GSPT1. We describe herein the structure–activity relationships for analogs of 3 with exploration of the structurally related dioxoisoindoline class.