Evidence map›Paper›PMID 34206631›Full record

ArticlePharmaceutics2021

An Effective and Safe Enkephalin Analog for Antinociception.

K K DurgaRao Viswanadham, Roland Böttger, Lukas Hohenwarter, Anne Nguyen, Elham Rouhollahi, Alexander Smith, Yi-Hsuan Tsai, Yuan-Yu Chang, Christopher Llynard Ortiz, Lee-Wei Yang and 4 more

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

Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 47% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. 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

14 authors at 2 institutions in 2 countries.

K K DurgaRao ViswanadhamFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Roland BöttgerFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.ORCID 0000-0002-5764-6844
Lukas HohenwarterFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Anne NguyenFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Elham RouhollahiFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Alexander SmithFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.ORCID 0000-0002-3489-4298
Yi-Hsuan TsaiInstitute of Bioinformatics and Structural Biology, National Tsing-Hua University, Hsinchu 300, Taiwan.
Yuan-Yu ChangPraexisio Taiwan Inc., Taipei 220, Taiwan.
Christopher Llynard OrtizInstitute of Bioinformatics and Structural Biology, National Tsing-Hua University, Hsinchu 300, Taiwan.ORCID 0000-0002-3114-7369
Lee-Wei YangInstitute of Bioinformatics and Structural Biology, National Tsing-Hua University, Hsinchu 300, Taiwan.ORCID 0000-0002-3971-6386
Liliana JimenezFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Siyuan LiFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Chan HurFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Shyh-Dar LiFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.ORCID 0000-0002-1763-2667
University of British Columbia · CANational Tsing Hua University · TW

Funding

Canada Foundation for Innovation 35816Canadian Cancer Society 706231Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada RGPIN-2017-03787CIHR PJT-148610CIHR PJT-168861Deutsche Forschungsgemeinschaft 423802991Michael Smith Foundation for Health Research 18711Mitacs IT13402National Organization for Rare Disorders 18004
6 · The paper itself

Abstract

Opioids account for 69,000 overdose deaths per annum worldwide and cause serious side effects. Safer analgesics are urgently needed. The endogenous opioid peptide Leu-Enkephalin (Leu-ENK) is ineffective when introduced peripherally due to poor stability and limited membrane permeability. We developed a focused library of Leu-ENK analogs containing small hydrophobic modifications. N-pivaloyl analog KK-103 showed the highest binding affinity to the delta opioid receptor (68% relative to Leu-ENK) and an extended plasma half-life of 37 h. In the murine hot-plate model, subcutaneous KK-103 showed 10-fold improved anticonception (142%MPE·h) compared to Leu-ENK (14%MPE·h). In the formalin model, KK-103 reduced the licking and biting time to ~50% relative to the vehicle group. KK-103 was shown to act through the opioid receptors in the central nervous system. In contrast to morphine, KK-103 was longer-lasting and did not induce breathing depression, physical dependence, and tolerance, showing potential as a safe and effective analgesic.

Indexed as

analgesicsdependenceenkephalinpainrespiratory suppressiontolerance

Identifiers

PMID34206631
PMCPMC8308721
OpenAlexW3173627931

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.