Evidence map›Paper›PMID 32876947›Full record

ArticleJournal of labelled compounds & radiopharmaceuticals2020

Synthesis of a deuterated 6-AmHap internal standard for the determination of hapten density in a heroin vaccine drug product.

Mariia Makarova, Rodell C Barrientos, Oscar B Torres, Gary R Matyas, Arthur E Jacobson, Agnieszka Sulima, Kenner C Rice

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

Article in Journal of labelled compounds & radiopharmaceuticals, 2020. 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
0.5field-weighted citation impact, top 41% 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. Article
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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

7 authors at 3 institutions in 1 country.

Mariia MakarovaDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Rodell C BarrientosLaboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Oscar B TorresLaboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Gary R MatyasLaboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Arthur E JacobsonDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Agnieszka SulimaDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.ORCID 0000-0002-8849-9736
Kenner C RiceDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
National Institute on Drug Abuse · USHenry M. Jackson Foundation · USWalter Reed Army Institute of Research · US

Funding

INTERACT Meeting with FDA on Cohort Design and Development of ALFQ as an Adjuvant for Heroin VaccineUG3DA048351 · NIDA · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI MATYAS, GARY R. · 2018 to 2019
$8.2M
Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Army Medical Research and Materiel Command 81XWH-07-2-067Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Army Medical Research and Materiel Command W81XWH-07-2-067Intramural NIH HHS Z99 DA999999NIDA NIH HHS UG3 DA048351NIH HHS 1UG3DA048351NIH Intramural Research Program (IRP) of the National Institute on Drug Abuse and the National Institute of Alcohol Abuse and Alcoholism
6 · The paper itself

Abstract

A deuterated hapten was designed and synthesized that will be essential for a future study of residual hapten and stability of a hapten-protein conjugate. This hapten, 6-AmHap, was chosen for a heroin vaccine that is now slated for a Phase 1 clinical trial. A maleimide-thiol bioconjugation strategy was successfully applied to our heroin vaccine to connect the hapten 6-AmHap with an immunogenic carrier protein (tetanus toxoid, TT) through a trityl-protected 3-mercaptopropanamide linker. The antibodies induced by the vaccine have been found to have activity against several opioids, including heroin and its metabolites, and, importantly, leave alternate pain treatment medications such as methadone untouched. To the best of our knowledge, no other hapten for a heroin vaccine has been deuterated, yet this tool may prove to be of great importance in the study of residual hapten during product release and the long-term stability program of a hapten-protein conjugate as part of FDA regulatory requirements. Hydrocodone was the starting material for the synthesis of the deuterated 6-AmHap, with a stable amide at C6 and a 3-mercaptopropanamide linker attached at C3. The desired deuterated product was prepared as the disulfide, 3,3'-disulfanediylbis(N-((7S,7aR,12bS)-7-acetamido-3-[

Indexed as

DeuteriumHaptensHeroinChemistry Techniques, SyntheticReference StandardsVaccinesDeuteriumHaptensHeroinVaccines6-AmHapdeuterated haptenhapten-protein conjugateheroin vaccinepreclinical study

Identifiers

PMID32876947
PMCPMC7717678
OpenAlexW3081627311

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.