GSK2982772

GSK2982772 : Inhibitor of RIPK1

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 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

RIPK1

Inhibitor

up to 300 nM

Probe Availability:

In Vitro Validations

Uniprot ID: Q13546

Target Class: Kinase

Target SubClass: TKL

Potency: IC50

Potency Value: 16 nM

Potency Assay: FP binding assay

PDB ID for probe-target interaction (3D structure): 5TX5

Structure-activity relationship: yes

Target aliases:

Receptor-interacting serine/threonine-protein kina ...

DOI Reference: 10.1021/acs.jmedchem.6b01751

Uniprot ID: Q13546

Target Class: Kinase

Target SubClass: TKL

Potency: IC50

Potency Value: 1 nM

Potency Assay: ADP-Glo Assay

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

Target aliases:

Receptor-interacting serine/threonine-protein kina ...

DOI Reference: 10.1021/acs.jmedchem.6b01751

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

GSK2982772 shows more than 1,000-fold selectivity for ERK5 over a panel of over 339 kinases Reaction Biology and on competition binding assay KINOMEscan at DiscoveRx Corp (456 kinases) both at 10 μM.

Probe Selectivity in Cell:

GSK2982772 demonstrated a clean profile against a range of nonkinase targets. No inhibitory potential toward recombinant human cytochrome P450 (CYP) enzymes, with the exception of weak activity against CYP2C9 (IC50 = 25 μM). Weak concentration-dependent inhibition of hERG in human embryonic kidney (HEK-293) cells, with an estimated IC50 of 195 μM, and showed a weak activation of the human Pregnane X receptor (hPXR) with an EC50 of 13 μM.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

The probe should be used in cellular system in combination with its enantiomer as negative control. Importantly, this probe shows significant species-differences as outlined by the authors in the J. Med. Chem. paper. Therefore, the probe can only be used in rodent acute models at relatively high doses (5-50 mg/Kg po, total systemic concentration significantly exceeding the recommended concentration range for cellular studies). When using the probe at these doses observed phenotypes will have to be linked back to on target activity by providing PK-PD correlations for proximal PD markers or the used of ko animals as controls.

(last updated: 2 Dec 2020 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

The enantiomer is very useful as a negative control probe. For orthogonal probe, e.g. in Cortellis Drug Discovery Intelligence there are 286 small molecules with Mw <750 g/mol that are used in either biological testing or preclinical phase as RIPK1 inhibitors.

(last updated: 14 Dec 2020 )

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 18 Dec 2020 )