Evidence map›Paper›PMID 26524472›Full record

ArticleJournal of medicinal chemistry2015

Further Optimization and Evaluation of Bioavailable, Mixed-Efficacy μ-Opioid Receptor (MOR) Agonists/δ-Opioid Receptor (DOR) Antagonists: Balancing MOR and DOR Affinities.

Aubrie A Harland, Larisa Yeomans, Nicholas W Griggs, Jessica P Anand, Irina D Pogozheva, Emily M Jutkiewicz, John R Traynor, Henry I Mosberg

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

Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

19 citing papers in PubMed, 38 citations in OpenAlex.

  1. Structural Modification and Development ofJournal of medicinal chemistry · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. NovelACS medicinal chemistry letters · 2020
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Novel Pharmacological Nonopioid Therapies in Chronic Pain.Current pain and headache reports · 2018
    Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. 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

8 authors at 1 institution in 1 country.

Aubrie A HarlandInterdepartmental Program in Medicinal Chemistry, ‡Department of Medicinal Chemistry, College of Pharmacy, and §Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
Larisa YeomansInterdepartmental Program in Medicinal Chemistry, ‡Department of Medicinal Chemistry, College of Pharmacy, and §Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
Nicholas W GriggsInterdepartmental Program in Medicinal Chemistry, ‡Department of Medicinal Chemistry, College of Pharmacy, and §Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
Jessica P AnandInterdepartmental Program in Medicinal Chemistry, ‡Department of Medicinal Chemistry, College of Pharmacy, and §Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
Irina D PogozhevaInterdepartmental Program in Medicinal Chemistry, ‡Department of Medicinal Chemistry, College of Pharmacy, and §Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
Emily M JutkiewiczInterdepartmental Program in Medicinal Chemistry, ‡Department of Medicinal Chemistry, College of Pharmacy, and §Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
John R TraynorInterdepartmental Program in Medicinal Chemistry, ‡Department of Medicinal Chemistry, College of Pharmacy, and §Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
Henry I MosbergInterdepartmental Program in Medicinal Chemistry, ‡Department of Medicinal Chemistry, College of Pharmacy, and §Department of Pharmacology, Medical School, University of Michigan , Ann Arbor, Michigan 48109, United States.
University of Michigan–Ann Arbor · US

Funding

INTERDEPARTMENTAL TRAINING IN PHARMACOLOGICAL SCIENCEST32GM007767 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ISOM, LORI L. · 1985 to 2019
$10.2M
Development of Mixed Function Opioid Peptides and PeptidomimeticsR01DA003910 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MOSBERG, HENRY ISAAC · 1985 to 2017
$9.0M
POSTDOCTORAL TRAINING IN THE BIOLOGY OF DRUG ABUSET32DA007268 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TRAYNOR, JOHN R. · 1991 to 2021
$6.7M
SUBSTANCE ABUSE INTERDISCIPLINARY TRAINING PROGRAMT32DA007267 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GNEGY, MARGARET E · 1994 to 2015
$4.5M
NIDA NIH HHS DA003910NIDA NIH HHS R01 DA003910NIDA NIH HHS T32 DA007267NIDA NIH HHS T32 DA007268NIGMS NIH HHS T32 GM007767
6 · The paper itself

Abstract

In a previously described peptidomimetic series, we reported the development of bifunctional μ-opioid receptor (MOR) agonist and δ-opioid receptor (DOR) antagonist ligands with a lead compound that produced antinociception for 1 h after intraperitoneal administration in mice. In this paper, we expand on our original series by presenting two modifications, both of which were designed with the following objectives: (1) probing bioavailability and improving metabolic stability, (2) balancing affinities between MOR and DOR while reducing affinity and efficacy at the κ-opioid receptor (KOR), and (3) improving in vivo efficacy. Here, we establish that, through N-acetylation of our original peptidomimetic series, we are able to improve DOR affinity and increase selectivity relative to KOR while maintaining the desired MOR agonist/DOR antagonist profile. From initial in vivo studies, one compound (14a) was found to produce dose-dependent antinociception after peripheral administration with an improved duration of action of longer than 3 h.

Indexed as

AcetylationAnalgesicsAnimalsBiological AvailabilityCHO CellsCricetinaeCricetulusDose-Response Relationship, DrugDrug DesignGuanosine 5'-O-(3-Thiotriphosphate)HumansInjections, IntraperitonealMaleMiceMice, Inbred C57BLPain MeasurementAnalgesicsGuanosine 5'-O-(3-Thiotriphosphate)Receptors, Opioid, deltaReceptors, Opioid, kappaReceptors, Opioid, mu

Identifiers

PMID26524472
PMCPMC4772774
OpenAlexW2336636627

What OpenQuestion holds

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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.