BIIB129

BIIB129 : Covalent Inhibitor of BTK

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

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Probe BIIB129 is in the process of SERP review.

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Information

Covalent Inhibitor

up to 1 µM
Reviewer recommended concentration: 100 nM

In Vitro Validations

Uniprot ID: Q06187

Target Class: Kinase

Target SubClass: Tyr kinase

Potency: Kd

Potency Value: 0.63 nM

Potency Assay: KinomeSCAN

PDB ID for probe-target interaction (3D structure): 8TU4

Target aliases:

Tyrosine-protein kinase BTK, AGMX1, BTK, BTK_HUMAN ...

DOI Reference: 10.1021/acs.jmedchem.4c00220

Uniprot ID: Q06187

Target Class: Kinase

Target SubClass: Tyr kinase

Potency: Activity

Potency Value: 4.6 (log kinact/Ki)

Potency Assay: continuous-read kinetic enzyme assay using the nonphosphorylated BTK protein

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

Target aliases:

Tyrosine-protein kinase BTK, AGMX1, BTK, BTK_HUMAN ...

DOI Reference: 10.1021/acs.jmedchem.4c00220

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): KINOMEscan, Eurofins DiscoverX, for BIIB129 was performed at 1 μM concentration. Ten and 5 out of 403 kinases were inhibited with S(10) selectivity scores of 0.025. BIIB129 showed greater than 10-fold selectivity for BTK over all but one (9-fold against TEC) of the 10 kinases tested.

Potency assay, off target (cells): BIIB129 shown to bind only 4 of 190 kinases (BTK TO50 = 6.8 nM, TEC TO50 = 18 nM, ITK TO50 = 308 nM and BLK TO50 = 3.9 nM) among 3500 total proteins detected when tested in a cellular matrix comprising of human Burkitt’s lymphoma cell line (Ramos), B cell lymphoma line (TMD8), and human T cell leukemia line (Jurkat) as a 1:1:1 mixture using kinomebead competitive chemoproteomics.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This BTK inhibitor has increased brain penetrance and a reasonable safety profile, making it a good probe of choice for studying BTK in neurological diseases. Its selectivity over most other kinases is also favorable, though users will have to keep an eye on BLK, TEC, and related kinases.

(last updated: 20 Aug 2025 )