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. 2023 Nov 17;14(12):1848–1856. doi: 10.1021/acsmedchemlett.3c00439

Figure 6.

Figure 6

(A) Crystal structure of compound 25 bound to the TKB/RING domain of Cbl-b (PDB code 8QNI). Compound 25 is in green, TKB domain in blue, and LHR in orange. Hydrogen bonds are shown as dashed lines; the putative intramolecular hydrogen bond is highlighted in red. (B) Western blot of a dose–response effect of Cbl-b inhibition on phosphorylation of PLCγ1 at Tyr783. Phosphorylated-PLCγ (pPLCγ) increases upon an increased dose of compound 25, in activated human T-cells. The left-most panel shows an unstimulated (UnStim) T-cell as a control, where the total PLCγ (TPLC) is completely unphosphorylated. (C) Inhibition of Cbl-b autoubiquitination via concentration-dependent dosing of compound 25. (D) Inhibition of Cbl-b ubiquitination of ZAP70 via concentration-dependent dosing of compound 25.