Evidence map›Paper›PMID 28775075›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2017

First Selective 12-LOX Inhibitor, ML355, Impairs Thrombus Formation and Vessel Occlusion In Vivo With Minimal Effects on Hemostasis.

Reheman Adili, Benjamin E Tourdot, Katherine Mast, Jennifer Yeung, John C Freedman, Abigail Green, Diane K Luci, Ajit Jadhav, Anton Simeonov, David J Maloney and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
6.4field-weighted citation impact, top 2% 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

70 citing papers in PubMed, 109 citations in OpenAlex.

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  10. The crucial role of thromboxane AFrontiers in pharmacology · 2026
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  15. Deficiency in platelet 12-lipoxygenase exacerbates inflammation and disease severity during SARS-CoV-2 infection.Proceedings of the National Academy of Sciences of the United States of America · 2025
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10 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 1 institution in 1 country.

Reheman AdiliFrom the Department of Pharmacology (R.A., B.E.T., K.M., J.Y., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Chemistry and Biochemistry, University of California Santa Cruz (J.C.F., A.G., T.R.H.); and National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Rockville, MD (D.K.L., A.J., A.S., D.J.M.).
Benjamin E TourdotFrom the Department of Pharmacology (R.A., B.E.T., K.M., J.Y., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Chemistry and Biochemistry, University of California Santa Cruz (J.C.F., A.G., T.R.H.); and National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Rockville, MD (D.K.L., A.J., A.S., D.J.M.).
Katherine MastFrom the Department of Pharmacology (R.A., B.E.T., K.M., J.Y., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Chemistry and Biochemistry, University of California Santa Cruz (J.C.F., A.G., T.R.H.); and National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Rockville, MD (D.K.L., A.J., A.S., D.J.M.).
Jennifer YeungFrom the Department of Pharmacology (R.A., B.E.T., K.M., J.Y., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Chemistry and Biochemistry, University of California Santa Cruz (J.C.F., A.G., T.R.H.); and National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Rockville, MD (D.K.L., A.J., A.S., D.J.M.).
John C FreedmanFrom the Department of Pharmacology (R.A., B.E.T., K.M., J.Y., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Chemistry and Biochemistry, University of California Santa Cruz (J.C.F., A.G., T.R.H.); and National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Rockville, MD (D.K.L., A.J., A.S., D.J.M.).
Abigail GreenFrom the Department of Pharmacology (R.A., B.E.T., K.M., J.Y., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Chemistry and Biochemistry, University of California Santa Cruz (J.C.F., A.G., T.R.H.); and National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Rockville, MD (D.K.L., A.J., A.S., D.J.M.).
Diane K LuciFrom the Department of Pharmacology (R.A., B.E.T., K.M., J.Y., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Chemistry and Biochemistry, University of California Santa Cruz (J.C.F., A.G., T.R.H.); and National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Rockville, MD (D.K.L., A.J., A.S., D.J.M.).
Ajit JadhavFrom the Department of Pharmacology (R.A., B.E.T., K.M., J.Y., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Chemistry and Biochemistry, University of California Santa Cruz (J.C.F., A.G., T.R.H.); and National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Rockville, MD (D.K.L., A.J., A.S., D.J.M.).
Anton SimeonovFrom the Department of Pharmacology (R.A., B.E.T., K.M., J.Y., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Chemistry and Biochemistry, University of California Santa Cruz (J.C.F., A.G., T.R.H.); and National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Rockville, MD (D.K.L., A.J., A.S., D.J.M.).
David J MaloneyFrom the Department of Pharmacology (R.A., B.E.T., K.M., J.Y., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Chemistry and Biochemistry, University of California Santa Cruz (J.C.F., A.G., T.R.H.); and National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Rockville, MD (D.K.L., A.J., A.S., D.J.M.).
Theodore R HolmanFrom the Department of Pharmacology (R.A., B.E.T., K.M., J.Y., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Chemistry and Biochemistry, University of California Santa Cruz (J.C.F., A.G., T.R.H.); and National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Rockville, MD (D.K.L., A.J., A.S., D.J.M.).
Michael HolinstatFrom the Department of Pharmacology (R.A., B.E.T., K.M., J.Y., M.H.) and Department of Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor; Chemistry and Biochemistry, University of California Santa Cruz (J.C.F., A.G., T.R.H.); and National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Rockville, MD (D.K.L., A.J., A.S., D.J.M.). mholinst@umich.edu.
University of California, Santa Cruz · US

Funding

Role of 12-lipoxygenase in platelet reactivity and type 2 diabetes mellitusR01HL114405 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HOLINSTAT, MICHAEL ALLAN · 2013 to 2017
$1.9M
12-HETrE regulation of plateletsR01GM105671 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HOLINSTAT, MICHAEL ALLAN · 2013 to 2017
$1.6M
Discovery of Potent 12-Lipoxygenase Inhibitors of Platelet ActivationR01AG047986 · NIA · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI HOLMAN, THEODORE R · 2014 to 2016
$1.4M
12-LOX inhibitors as Potential Anti-Platelet TherapeuticsZIATR000194 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI SIMEONOV, ANTON · 2015 to 2021
$1.2M
Pharmacogenomics studies of PAR4 regulation in human plateletsF32HL129491 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TOURDOT, BENJAMIN ERIC · 2015 to 2017
$136k
12-lipoxygenase regulation of FcgRIIa-mediated platelet activationF31HL129481 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI YEUNG, JENNIFER · 2015 to 2017
$106k
NHLBI NIH HHS F31 HL129481NHLBI NIH HHS F32 HL129491NHLBI NIH HHS R01 HL114405NIA NIH HHS R01 AG047986NIGMS NIH HHS R01 GM105671
6 · The paper itself

Abstract

objectiveAdequate platelet reactivity is required for maintaining hemostasis. However, excessive platelet reactivity can also lead to the formation of occlusive thrombi. Platelet 12(S)-lipoxygenase (12-LOX), an oxygenase highly expressed in the platelet, has been demonstrated to regulate platelet function and thrombosis ex vivo, supporting a key role for 12-LOX in the regulation of in vivo thrombosis. However, the ability to pharmacologically target 12-LOX in vivo has not been established to date. Here, we studied the effect of the first highly selective 12-LOX inhibitor, ML355, on in vivo thrombosis and hemostasis. APPROACH AND

resultsML355 dose-dependently inhibited human platelet aggregation and 12-LOX oxylipin production, as confirmed by mass spectrometry. Interestingly, the antiplatelet effects of ML355 were reversed after exposure to high concentrations of thrombin in vitro. Ex vivo flow chamber assays confirmed that human platelet adhesion and thrombus formation at arterial shear over collagen were attenuated in whole blood treated with ML355 comparable to aspirin. Oral administration of ML355 in mice showed reasonable plasma drug levels by pharmacokinetic assessment. ML355 treatment impaired thrombus growth and vessel occlusion in FeCl

conclusionsOur data strongly support 12-LOX as a key determinant of platelet reactivity in vivo, and inhibition of platelet 12-LOX with ML355 may represent a new class of antiplatelet therapy.

Indexed as

AnimalsBenzenesulfonamidesDose-Response Relationship, DrugHemostasisHumansLipoxygenase InhibitorsMicePlatelet AdhesivenessPlatelet AggregationSulfonamidesThrombinThrombosisBenzenesulfonamidesLipoxygenase InhibitorsML355SulfonamidesThrombincollagenhemostasislipoxygenaseplatelet reactivitythrombosis

Identifiers

PMID28775075
PMCPMC5620123
OpenAlexW2743072594

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.