Evidence map›Paper›PMID 36484496›Full record

ArticleMolecular pharmaceutics2023

NPP-669, a Novel Broad-Spectrum Antiviral Therapeutic with Excellent Cellular Uptake, Antiviral Potency, Oral Bioavailability, Preclinical Efficacy, and a Promising Safety Margin.

Elke Lipka, Aaron M Chadderdon, Cheryl C Harteg, Matthew K Doherty, Eric S Simon, John M Domagala, Dawn M Reyna, Kim M Hutchings, Xinmin Gan, Andrew D White and 11 more

Open access · greenAbstract read
In one paragraph

Article in Molecular pharmaceutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.3field-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

6 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Mpox (formerly monkeypox): pathogenesis, prevention, and treatment.Signal transduction and targeted therapy · 2023
    Review
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

21 authors at 6 institutions in 1 country.

Elke LipkaTSRL, Inc., 540 Avis Dr., Suite A, Ann Arbor, Michigan 48108, United States.
Aaron M ChadderdonTSRL, Inc., 540 Avis Dr., Suite A, Ann Arbor, Michigan 48108, United States.
Cheryl C HartegTSRL, Inc., 540 Avis Dr., Suite A, Ann Arbor, Michigan 48108, United States.
Matthew K DohertyTSRL, Inc., 540 Avis Dr., Suite A, Ann Arbor, Michigan 48108, United States.ORCID 0000-0003-4782-1802
Eric S SimonTSRL, Inc., 540 Avis Dr., Suite A, Ann Arbor, Michigan 48108, United States.
John M DomagalaTSRL, Inc., 540 Avis Dr., Suite A, Ann Arbor, Michigan 48108, United States.
Dawn M ReynaTSRL, Inc., 540 Avis Dr., Suite A, Ann Arbor, Michigan 48108, United States.
Kim M HutchingsCollege of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.
Xinmin GanCollege of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.
Andrew D WhiteCollege of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.
Caroll B HartlineDepartment of Pediatrics, University of Alabama School of Medicine, Birmingham, Alabama 35233, United States.
Emma A HardenDepartment of Pediatrics, University of Alabama School of Medicine, Birmingham, Alabama 35233, United States.
Kathy A KeithDepartment of Pediatrics, University of Alabama School of Medicine, Birmingham, Alabama 35233, United States.
Mark N PrichardDepartment of Pediatrics, University of Alabama School of Medicine, Birmingham, Alabama 35233, United States.
Scott H JamesDepartment of Pediatrics, University of Alabama School of Medicine, Birmingham, Alabama 35233, United States.
Rhonda D CardinSchool of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
David I BernsteinCincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, United States.
Jacqueline F SpencerSaint Louis University School of Medicine, St. Louis, Missouri 63104, United States.
Ann E TollefsonSaint Louis University School of Medicine, St. Louis, Missouri 63104, United States.
William S M WoldSaint Louis University School of Medicine, St. Louis, Missouri 63104, United States.
Karoly TothSaint Louis University School of Medicine, St. Louis, Missouri 63104, United States.
Therapeutics Systems Research Laboratories (United States) · USUniversity of Alabama · USSaint Louis University · USUniversity of Michigan · USCincinnati Children's Hospital Medical Center · USLouisiana State University · US

Funding

Broad Spectrum Antiviral Nucleoside Phosphonate AnalogsR44AI100401 · NIAID · TSRL, INC. · PI LIPKA, ELKE · 2015 to 2017
$3.0M
TASK B26: COMPREHENSIVE VIRAL SCREENING PANEL.75N93019D00016 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI JAMES, SCOTT · 2019 to 2025
$2.8M
New Prodrug Strategies for Cidofovir Designed for Mitigating First-Pass MetabolismR03AI135760 · NIAID · TSRL, INC. · PI LIPKA, ELKE · 2018 to 2019
$203k
NIAID NIH HHS 75N93019D00016NIAID NIH HHS HHSN272201800001GNIAID NIH HHS HHSN272201800001INIAID NIH HHS R03 AI135760NIAID NIH HHS R44 AI100401
6 · The paper itself

Abstract

DNA viruses are responsible for many diseases in humans. Current treatments are often limited by toxicity, as in the case of cidofovir (CDV, Vistide), a compound used against cytomegalovirus (CMV) and adenovirus (AdV) infections. CDV is a polar molecule with poor bioavailability, and its overall clinical utility is limited by the high occurrence of acute nephrotoxicity. To circumvent these disadvantages, we designed nine CDV prodrug analogues. The prodrugs modulate the polarity of CDV with a long sulfonyl alkyl chain attached to one of the phosphono oxygens. We added capping groups to the end of the alkyl chain to minimize β-oxidation and focus the metabolism on the phosphoester hydrolysis, thereby tuning the rate of this reaction by altering the alkyl chain length. With these modifications, the prodrugs have excellent aqueous solubility, optimized metabolic stability, increased cellular permeability, and rapid intracellular conversion to the pharmacologically active diphosphate form (CDV-PP). The prodrugs exhibited significantly enhanced antiviral potency against a wide range of DNA viruses in infected human foreskin fibroblasts. Single-dose intravenous and oral pharmacokinetic experiments showed that the compounds maintained plasma and target tissue levels of CDV well above the EC

Indexed as

Cytomegalovirus InfectionsOrganophosphonatesProdrugsAnimalsAntiviral AgentsBiological AvailabilityCidofovirCytosineHumansMiceAntiviral AgentsCidofovirCytosineOrganophosphonatesProdrugsadenovirusantiviralcidofovir prodrugcytomegalovirusDNA virusesintracellular metabolism

Identifiers

PMID36484496
PMCPMC9811456
OpenAlexW4310917389

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.