Capzimin

Capzimin : Inhibitor of Rpn11

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(0 ratings)

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Probe Capzimin is in the process of SERP review.

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Information

PSMD14

Inhibitor

up to 10 uM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: O00487

Target Class: Enzyme

Target SubClass: Peptidase

Potency: IC50

Potency Value: 360 nM

Potency Assay: Fluorescence polarization assays

PDB ID for probe-target interaction (3D structure): --

Target aliases:

26S proteasome non-ATPase regulatory subunit 14, P ...

DOI Reference: 10.1038/nchembio.2326

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Capzimin showed 80-fold selectivity for Rpn11 over Csn5, ten-fold over AMSH and six-fold over BRCC36 (IC50s = 30 μM, 4.5 μM, and 2.3 μM, respectively). Outside target family: Assayed on other metalloenzymes (HDAC6, MMP 2, MMP 12, hCAII, GLO1) with IC50s exceeding 40 uM

Potency assay, off target (cells): Capzimin was screened against the NCI panel of 60 cancer cell lines31. The median GI50 was 3.3 μM (Supplementary Fig. 15). Capzimin exhibited promising activity in leukemia cells including the SR and K562 cell lines (GI50 values of 0.67 μM and 1 μM, respectively) as well as several solid tumor cell lines including NCI-H460 (non-small-cell lung cancer; GI50 = 0.7 μM) and MCF7 (breast cancer; GI50 = 1.0 μM) (DOI: 10.1038/nchembio.2326)

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

The compound elicits a phenotype that is consistent with inhibition of proteasomal deubiquitination by PSMD14 and is distinct from proteasome inhibitors targeting the catalytic subunits. However, researchers who want to use the compound for cellular assays need to be aware that the in vitro potency of the compound was determined against the yeast orthologue Rpn11 (which is only 64% identical to PSMD14). In vitro potency data against the human PSMD14 protein is lacking, and as such the specificity window against other JAMM DUBs in human cells is unclear. With more data on Capzimin's ability to inhibit human PSDM14, the rating of the compound could be increased. The required concentrations for the cellular use (2-10 µM) are near the IC50 values for some human JAMM orthologues (which are 2-4 µM). Researchers are thus advised to take this into account when evaluating their results. Still, there currently is no better alternative for adressing PSMD14 in cells and use of this compound is thus encouraged with caution.

(last updated: 7 Nov 2023 )