Structures of human telomerase with BIBR1532 reveal novel mechanism of inhibition.

Yuqing Wang, Baocheng Liu, Yao He, Juli Feigon

Abstract read

In one paragraph

Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing 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

1 citing paper in PubMed.

The Different Faces of the Selective Human Telomerase Inhibitor: BIBR1532 and Its Derivatives.Current issues in molecular biology · 2026
Article

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

4 authors.

Yuqing Wang *Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-5551-3469

Baocheng Liu *Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-7895-9455

Yao HeDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-1368-6422

Juli FeigonDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA. feigon@mbi.ucla.edu.ORCID http://orcid.org/0000-0003-3376-435X

Funding

Structural biology of telomerase and telomeresR35GM131901 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JULI FEIGON · 2019 to 2026

$5.7M

National Science Foundation (NSF) MCB2016540U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM131901

6 · The paper itself

Abstract

Human telomerase processively adds telomeric repeats (dGGTTAG) to chromosome 3'-ends to maintain telomere length. While mostly absent in somatic cells, telomerase is aberrantly upregulated in most tumor cells to sustain cellular immortality, making it a promising oncology target. However, to date there are no reported structures of human telomerase with inhibitor, impeding structure-based drug design and optimization. We report nine cryo-electron microscopy structures of human telomerase with and without BIBR1532, a highly selective small-molecule telomerase inhibitor. Unexpectedly, BIBR1532 binds a previously unknown pocket between TERT finger and palm. BIBR1532 inhibits each step but disproportionately affects the rate-limiting first step of telomere repeat nucleotide addition. The structures reveal a rigid finger that explains telomerase's slow rate and low fidelity. Our study provides insights into telomerase catalytic mechanism and its inhibition by BIBR1532, explains why prior BIBR derivatives did not improve potency and suggests a rational approach for design of small-molecule telomerase inhibitors.

Identifiers

PMID42230822

DOI10.1016/j.bpj.2023.07.019

What OpenQuestion holds

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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 OpenQuestion graph.