Extended Data Fig. 1: Targeting high-efficiency β-catenin protein degradation in B-cell leukemia. | Nature Cancer

Extended Data Fig. 1: Targeting high-efficiency β-catenin protein degradation in B-cell leukemia.

From: Targeting β-catenin degradation with GSK3β inhibitors induces cell death in acute lymphoblastic leukemia

Extended Data Fig. 1

(a) In epithelial cancers (left) efficiency of β-catenin protein degradation is low and further reduced by oncogenic mutations. β-catenin accumulates and pairs with TCF factors for transcriptional activation of MYC. In B-cell leukemia (middle) β-catenin is constitutively phosphorylated by GSK3B and targeted for B-cell-specific high-efficiency protein degradation. GSK3B-inhibitors impair β-catenin protein degradation (right) and β-catenin accumulates in the nucleus. Instead of TCF, β-catenin pairs with Ikaros and NuRD factors for MYC repression (right). b) Summary of Phase I and Phase II clinical trials with GSK3β inhibitors for a variety of clinical indications. In a total of 20 clinical trials, all tested small molecule inhibitors achieved favorable safety and PK/PD profiles at micromolar plasma concentrations (Cmax). None of the inhibitors achieved clinical responses. Moderate adverse effects included diarrhea, anemia and lymphopenia.

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