TP-008

TP-008 : Inhibitor of ACVR1B, TGFBR1

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(0 ratings)

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Probe TP-008 is in the process of SERP review.

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Information

ACVR1B
TGFBR1

Inhibitor

1-10 uM

Additional Data

SGC image SGC Chemical Probe Collection

Probe Availability:

In Vitro Validations

Uniprot ID: P36896

Target Class: Kinase

Target SubClass: TKL

Potency: IC50

Potency Value: 25 nM

Potency Assay: Lanthascreen

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

Target aliases:

Activin receptor type-1B, ALK4, ACVRLK4, ACVR1B, A ...

DOI Reference: 10.1021/acschembio.0c00076

Uniprot ID: P36896

Target Class: Kinase

Target SubClass: TKL

Potency: IC50

Potency Value: 300 nM

Potency Assay: Radioactive kinase assay (Reaction Biology)

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

Target aliases:

Activin receptor type-1B, ALK4, ACVRLK4, ACVR1B, A ...

DOI Reference: 10.1021/acschembio.0c00076

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

Clean KINOMEscan; off targets > 20 µM in NanoBRET. Selectivity outside target family: Closest off-targets: HTR2B 65% inhibition, PDE10A 73% inhibition (Diversity panel (Ricerca) results at 10 µM). Clean GPCR scan except for activity on HTR2B (70 % inhibition, Ki = 1881 nM)

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SERP ratings and comments

SERP+ Ratings

In Cell Rating

SERP+ Comments:

The compound is very well characterised but potency varies significantly, between the different assays. The IC50 values determined in the radioactive kinase assay are high for a chemical probe (345 nM ALK5). The cellular data for the NanoBRET is slightly to high (5,7 uM for ALK5) but lower in a reporter assay with IC50s of about (245 nM for ALK5 and 526 nM for ALK4). potentially, high concentrations (double-digit µM range) will have to be used to reach IC95. The selectivity assay has shown no off targets at 1 uM but this concentration was not high enough to show 30 fold selectivity. The compound has good working control compounds but shows heart toxicity.

(last updated: 17 Jun 2024 )