JNJ-42396302

JNJ-42396302 : Inhibitor of PDE10A

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

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Probe JNJ-42396302 is in the process of SERP review.

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Information

PDE10A

Inhibitor

up to 10 uM

Additional Data

SGC image SGC Chemical Probe Collection

Probe Availability:

MCULE

In Vitro Validations

Uniprot ID: Q9Y233

Target Class: Enzyme

Target SubClass: Phosphodiesterase

Potency: Ki

Potency Value: 13 nM

Potency Assay: SPA using human PDE10A and [3H]cAMP substrate

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

Target aliases:

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphod ...

DOI Reference: 10.6019/CHEMBL4800727

Uniprot ID: Q9Y233

Target Class: Enzyme

Target SubClass: Phosphodiesterase

Potency: IC50

Potency Value: 40 nM

Potency Assay: Inhibition of cAMP hydrolysis by isolated hPDE10A enzyme

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

Target aliases:

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphod ...

DOI Reference: 10.6019/CHEMBL4800727

Uniprot ID: Q9Y233

Target Class: Enzyme

Target SubClass: Phosphodiesterase

Potency: IC50

Potency Value: 51 nM

Potency Assay: Inhibition of cGMP hydrolysis by isolated hPDE10A enzyme

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

Target aliases:

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphod ...

DOI Reference: 10.6019/CHEMBL4800727

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

Selectivity within target family: PDE selectivity > 250 fold: closest hit is PDE1B with Ki = 3.4 µM (257 fold). Selectivity outside target family: CEREP receptor and enzyme panel (50) at 10 µM: clean; Millipore kinase panel (203) at 10 µM: all inhibition < 50 %

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Based on the information provided in the pdf file the compound looks potent, selective, and cell-permeable. I would recommend to use JNJ-42396302 as a chemical probe both in vitro and in cell-based assays. The compound shows high binding affinity (Ki = 13 nM) against PDE10A in vitro and great > 250-fold selectivity against other PDEs. The compound is also inactive or weak against a broad panel of enzymes at up to 10uM concentration. The data demonstrate the on-target activity of the compound in the HEK293 cells 1-10uM concentration range in a luciferase reporter assay. Suggesting that the compound is cell-permeable and active in cell-based assays. However, a direct target engagement (binding tp PDE10A) in cells is not shown. The rat studies demonstrate the tolerance to up to 40mg/kg of JNJ-42396302, and the determined ED50 0f 1.4 mg/kg demonstrates the potency of the compound in vivo.

(last updated: 1 Jul 2022 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Limited cell assay data is made available, with the increase in observed effects between 2.3 and 10 µM suggesting a cellular potency >5 µM (significant uncertainty in this estimate). In addition, cell data is only shown for overexpressed mouse enzyme in a HEK293 cell background and with a two orders of magnitude drop-off from the biochemical data. A mechanistic understanding of this drop-off is needed to understand probe fitness for cellular studies.

(last updated: 4 Jul 2022 )