JPS016

JPS016 : Degrader (PROTAC) of HDAC1, HDAC2, HDAC3

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(0 ratings)

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Probe JPS016 is in the process of SERP review.

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Information

HDAC1
HDAC2
HDAC3

Degrader (PROTAC)

In Vitro Validations

Uniprot ID: Q13547

Target Class: Epigenetic

Target SubClass: HDAC

Potency: IC50

Potency Value: 570 nM

Potency Assay: Histone Deacetylase Assay HDAC1-LSD1-CoREST complex

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

Target aliases:

Histone deacetylase 1, RPD3L1, HDAC1, HDAC1_HUMAN, ...

DOI Reference: 10.1021/acs.jmedchem.1c02179

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay, off target (cells): RNA sequencing was performed to assess differentially expressed gene (DEG) in HTT16 cells. Inhibitor CI994 and PROTAC JPS016 were assessed, showing that both inhibition and degradation produce a strong antiproliferative phenotype in cancer cells. JPS016 exhibited the greatest level of differential gene expression with 2464 and 1477 up- and downregulated DEGs, respectively.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

The parental compound CI-994 (as well as its PROTAC derivative JPS016) was mainly developed with the demonstrated inhibition of HDAC1-3. The potential off-target effects of the parent compound have not yet assessed for other proteins, particularly other HDACs and diverse metal-containing proteins in vitro and in cellular contexts. In addition, no mode of interaction of CI-994 and JPS016 was examined in great details. The reviewer has the concern of broad off-target effects without further characterization. The data in the JMC paper of 2022 showed a very narrow range of the varied hook effects on HDAC1-3 in HCT116 cells. Given that only one cell line was examined and the different degradation efficiency against HDAC1-3, the reviewer strongly recommended conducting the titration curves of HDAC1-3 in different cell lines and then decided the optimal concentrations case by case.

(last updated: 23 Feb 2025 )