TL13-112

TL13-112 : Degrader (PROTAC) of ALK

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe TL13-112 is in the process of SERP review.

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Information

Degrader (PROTAC)

250 nM, up to 1 uM

DOI - 10.1021/acs.jmedchem.7b01655

Probe Availability:

In Vitro Validations

Uniprot ID: Q9UM73

Target Class: Kinase

Target SubClass: RTK

Potency: IC50

Potency Value: 0.6 nM

Potency Assay: ALK LANCE Activity Assay at ATP Km (18µM)

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

Structure-activity relationship: no

Target aliases:

ALK tyrosine kinase receptor, ALK, ALK_HUMAN, Anap ...

DOI Reference: 10.1021/acs.jmedchem.7b01655

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Probe Selectivity in Cell:

Degradation of targets other than ALK, including PTK2, FER, RPS6KA1, and Aurora A, was measured at significant levels with proteomic MS and confirmed by Western blot.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

The strong point of the publication revealing TL13-112 is the broad profiling of the PROTAC against many cell lines across range of different time points and concentrations. Also the mechanism of action was relatively well investigated by competition with parent ligands or by co-treatment with neddylation inhibitor or proteasomal inhibitor. The selectivity of degradation has been evaluated using MS-proteomics at 4 h time point, showing a few off-targets (PTK2, FER, Aurora A, ZNF692) but only very weak ALK degradation. It is unclear what would be the selectivity profile under more relevant conditions that would lead to higher ALK depletion. Currently (April 2024) there are better ALK degraders published that could be used as tool compounds.

(last updated: 23 Apr 2024 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

.Care should be taken that at concentrations higher than the recommended 10 nM, other kinases such as RPS6KA3 might be degraded, judged from the proteomics profile.

(last updated: 31 Oct 2024 )