SGC-GAK-1

SGC-GAK-1 : Inhibitor of GAK

Structure

SERP Rating

In Cells

(3 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.

Information

Inhibitor

up to 1 µM; use with appropriate control compounds

Additional Data

SGC Chemical Probe Collection

Probe Availability:

MCULE

In Vitro Validations

Uniprot ID: O14976

Target Class: Kinase

Target SubClass: Ser/Thr Kinase

Potency: Kd

Potency Value: 1.9 nM

Potency Assay: Competition binding assay (DiscoverX)

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

Target aliases:

Cyclin-G-associated kinase, GAK, GAK_HUMAN

DOI Reference: 10.1021/acs.jmedchem.8b01213

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

No kinases were observed to bind SGC-GAK-1 within 30-fold of the KD of GAK in a KINOMEscan assay (DiscoverX) at 1 μM followed by KD determinations.

Probe Selectivity in Cell:

Despite weakly binding RIPK2 in vitro (DiscoverX RIPK2 KD = 110 nM; 58-fold of GAK KD), SGC-GAK-1 potently engaged RIPK2 in a live cell NanoBRET assay (RIPK2 IC50 = 360 nM); a control compound that is a highly cell-potent RIPK2 ligand, HY-19764, (IC50 = 2.2 nM) that lacks GAK affinity (IC50 > 10 µM) is available.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

This set of probes, including SGC-GAK-1 and SGC-GAK-1N and KA2 together represent the current best available chemical tools for deciphering GAK function in cells. KINOMEscan and cellular nanobret target engagement data together support SGC-GAK-1 as a highly selective and potent cellular probe molecule.

(last updated: 21 Jun 2022 )

SERP Ratings

In Cell Rating

SERP Comments:

Partial engagement of RIPK2 was reported at 1µM, effects at higher concentrations should be interpreted accordingly

(last updated: 6 Jul 2022 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

Cellular engagement with RIPK2 was reported at 0.4µM, hence the probe should be used in combination with selective RIPK2 inhibitors (e.g., HY-19764) as an orthogonal tool.

(last updated: 22 Mar 2023 )