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Figure 4
GND-135 has com­parable in vivo efficacy com­pared to CB-5083. (a) In vivo efficacy of GND-135 versus CB-5083 in the U937 CDX model. Tumor growth versus days post cell implantation for untreated and treated groups. CB-5083 was administered at 40 mg/kg QD, PO, and GND-135 was administered at 40 mg/kg QD, IP. (b) %Body weight change versus days post cell implantation. Data are represented as mean ± SEM. (c) Synergistic relation between cryo-EM map resolution and com­pound potency. As the potency of the com­pound is im­proved with the progression from an H atom to an amide moiety to a sulfonamide moiety, there are more inter­actions in the binding pocket. In turn, this likely results in reduced flexibility of the com­pound. Because VCP/p97 is a dynamic allosteric protein where active site inhibitors bound to D2 restrict conformational flexibility, an increase in local resolution at the binding site driven by more inter­actions is also partially reflected in the resolution of the overall density map.

IUCrJ
Volume 13| Part 4| July 2026|
ISSN: 2052-2525
https://doi.org/10.1107/S2052252526004604