Evidence map›Paper›PMID 42465337›Full record

ArticlebioRxiv : the preprint server for biology2026

Stereoselective Covalent Targeting of BTK(C481S) and Kinases with β-Lactone Electrophiles.

Celine D Wang, Polina E Barzova, Julian Robles, Ethan S Toriki, Francisco J Garcia, Jeffrey M McKenna, Markus Schirle, Ziyang Zhang

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Celine D WangDepartment of Chemistry, University of California, Berkeley, California 94720, USA.ORCID 0000-0001-8190-1043
Polina E BarzovaDepartment of Chemistry, University of California, Berkeley, California 94720, USA.
Julian RoblesDepartment of Chemistry, University of California, Berkeley, California 94720, USA.
Ethan S TorikiNovartis-Berkeley Translational Chemical Biology Institute, Berkeley, California 94720, USA.
Francisco J GarciaNovartis-Berkeley Translational Chemical Biology Institute, Berkeley, California 94720, USA.
Jeffrey M McKennaNovartis-Berkeley Translational Chemical Biology Institute, Berkeley, California 94720, USA.
Markus SchirleNovartis-Berkeley Translational Chemical Biology Institute, Berkeley, California 94720, USA.
Ziyang ZhangDepartment of Chemistry, University of California, Berkeley, California 94720, USA.ORCID 0000-0003-3836-6473

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The cysteine to serine mutation at residue 481 of Bruton's tyrosine kinase (BTK) is the most common mechanism of clinical resistance against ibrutinib for the treatment of mantle cell lymphoma and chronic lymphocytic leukemia. We report small molecule ligands containing chiral β-lactone electrophiles to address this challenge. The asymmetric warhead enabled stereoselective covalent modification of wild-type and ibrutinib-resistant mutant BTK(C481S) through distinct sites of reactivity. Building on these findings, we developed kinase-directed β-lactone probes and demonstrated that individual enantiomers preferentially engage distinct subsets of the kinome. These studies establish β-lactones as stereochemically encodable covalent warheads whose stereochemistry can serve as a selectivity filter in covalent drug discovery.

Identifiers

PMID42465337
PMCPMC13370387

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.