SGC-CDKL5_GSK3

SGC-CDKL5_GSK3 : ATP competitive, Inhibitor of CDKL5, GSK3A, GSK3B

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Probe SGC-CDKL5_GSK3 is in the process of SERP review.

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Information

CDKL5
GSK3A
GSK3B

ATP competitive
Inhibitor

up to 500 nM

Additional Data

SGC Chemical Probe Collection

In Vitro Validations

Uniprot ID: O76039

Target Class: Kinase

Target SubClass: CMGC

Potency: IC50

Potency Value: 6.5 nM

Potency Assay: CDKL5 Split luciferase assay

PDB ID for probe-target interaction (3D structure): 8CIE

Target aliases:

Cyclin-dependent kinase-like 5, STK9, CDKL5, CDKL5 ...

DOI Reference: 10.1021/acschemneuro.3c00135

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Compounds 2 and 4, were analysed at 1 μM in the Eurofins DiscoverX scanMAX panel, assessing binding to 403 Kinases: both compounds were shown to be selective for CDKL5 except for GSK3a/b. Within the CDKL family, compound 2 was selective, showing DiscoverX percent control values of 89 (CDKL2), 95 (CDKL1) and 100 (CDKL3).

Potency assay, off target (cells): NanoBRET assay for closest off-target CDK16 and related CDK17: IC50 of 1.9 μM for bot targets

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

The probe is highly potent in cellular and cell free settings, was assessed thoroughly and screened against a panel of 402 kinases (Eurofins DiscoverX scanMAX) without any additional off targets. A control compound that only targets GSK3 is provided and should be used to assess CDKL5 mediated effects. Considering the selectivity limitations, the probe is recommendable. Additional note: The group who reported the probe by now reported a full selective probe on CDKL5 (10.7554/eLife.88206).

(last updated: 17 Jun 2024 )

SERP+ Ratings

In Cell Rating

(last updated: 23 Sept 2024 )