Evidence map›Paper›PMID 32042200›Full record

ArticleNature chemical biology2020

Development of a covalent inhibitor of gut bacterial bile salt hydrolases.

Arijit A Adhikari, Tom C M Seegar, Scott B Ficarro, Megan D McCurry, Deepti Ramachandran, Lina Yao, Snehal N Chaudhari, Sula Ndousse-Fetter, Alexander S Banks, Jarrod A Marto and 2 more

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 2 pooled it
5.2field-weighted citation impact, top 3% of its field
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

78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 112 citations in OpenAlex.

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  20. Enzymatic carbon-fluorine bond cleavage by human gut microbes.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article

18 more citing papers are in PubMed but not listed here.

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

12 authors at 3 institutions in 1 country.

Arijit A AdhikariDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Tom C M SeegarDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Scott B FicarroDepartment of Cancer Biology, Department of Oncologic Pathology, Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA, USA.
Megan D McCurryDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3231-8876
Deepti RamachandranDivision of Endocrinology, Metabolism, and Diabetes, Beth Israel Deaconness Medical Center, Boston, MA, USA.
Lina YaoDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1018-5646
Snehal N ChaudhariDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Sula Ndousse-FetterDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Alexander S BanksDivision of Endocrinology, Metabolism, and Diabetes, Beth Israel Deaconness Medical Center, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1787-6925
Jarrod A MartoDepartment of Cancer Biology, Department of Oncologic Pathology, Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2086-1134
Stephen C BlacklowDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6904-1981
A Sloan DevlinDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA. sloan_devlin@hms.harvard.edu.ORCID http://orcid.org/0000-0001-5598-3751
Harvard University · USBeth Israel Deaconess Medical Center · USBrigham and Women's Hospital · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WAYNE I LENCER · 1986 to 2026
$32.4M
Notch Signaling in CancerR35CA220340 · NCI · HARVARD MEDICAL SCHOOL · PI BLACKLOW, STEPHEN C. · 2017 to 2023
$7.1M
Human microbiome metabolites in health and diseaseR35GM128618 · NIGMS · HARVARD MEDICAL SCHOOL · PI Abigail Sloan Devlin · 2018 to 2026
$4.1M
EZH2 in cancer biology and novel inhibitorsR01CA222218 · NCI · DANA-FARBER CANCER INST · PI QI, JUN · 2018 to 2022
$2.6M
NCI NIH HHS R01 CA222218NCI NIH HHS R35 CA220340NIDDK NIH HHS P30 DK034854NIGMS NIH HHS R35 GM128618
6 · The paper itself

Abstract

Bile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. Bile acids regulate key metabolic and immune processes by binding to host receptors. There is an unmet need for a potent tool to inhibit BSHs across all gut bacteria to study the effects of bile acids on host physiology. Here, we report the development of a covalent pan-inhibitor of gut bacterial BSHs. From a rationally designed candidate library, we identified a lead compound bearing an alpha-fluoromethyl ketone warhead that modifies BSH at the catalytic cysteine residue. This inhibitor abolished BSH activity in conventional mouse feces. Mice gavaged with a single dose of this compound displayed decreased BSH activity and decreased deconjugated bile acid levels in feces. Our studies demonstrate the potential of a covalent BSH inhibitor to modulate bile acid composition in vivo.

Indexed as

AmidohydrolasesAnimalsBacteriaBile Acids and SaltsDrug DesignFemaleGastrointestinal MicrobiomeHumansMaleMiceMice, Inbred C57BLSmall Molecule LibrariesAmidohydrolasesBile Acids and Saltscholoylglycine hydrolaseSmall Molecule Libraries

Identifiers

PMID32042200
PMCPMC7036035
OpenAlexW3004986543

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.