Evidence map›Paper›PMID 37949450›Full record

ArticleJournal of medicinal chemistry2023

Discovery of

Kateřina Novotná, Lukáš Tenora, Eva Prchalová, James Paule, Jesse Alt, Vijay Veeravalli, Jenny Lam, Ying Wu, Ivan Šnajdr, Sadakatali Gori and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. 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

15 authors at 3 institutions in 2 countries.

Kateřina NovotnáInstitute of Organic Chemistry and Biochemistry v.v.i., Academy of Sciences of the Czech Republic, Prague 160 00, Czech Republic.ORCID 0000-0003-0202-5132
Lukáš TenoraInstitute of Organic Chemistry and Biochemistry v.v.i., Academy of Sciences of the Czech Republic, Prague 160 00, Czech Republic.
Eva PrchalováInstitute of Organic Chemistry and Biochemistry v.v.i., Academy of Sciences of the Czech Republic, Prague 160 00, Czech Republic.
James Paule
Jesse Alt
Vijay Veeravalli
Jenny Lam
Ying Wu
Ivan ŠnajdrInstitute of Organic Chemistry and Biochemistry v.v.i., Academy of Sciences of the Czech Republic, Prague 160 00, Czech Republic.ORCID 0000-0002-0831-4034
Sadakatali Gori
Vijaya Saradhi Mettu
Takashi TsukamotoORCID 0000-0002-0216-7520
Pavel MajerInstitute of Organic Chemistry and Biochemistry v.v.i., Academy of Sciences of the Czech Republic, Prague 160 00, Czech Republic.
Barbara S SlusherORCID 0000-0001-9814-4157
Johns Hopkins University · USCzech Academy of Sciences, Institute of Organic Chemistry and Biochemistry · CZCharles University · CZ

Funding

Cell-targeted glutamine antagonists as a novel therapy for lymphomaR01CA229451 · NCI · JOHNS HOPKINS UNIVERSITY · PI SLUSHER, BARBARA STAUCH · 2018 to 2022
$2.3M
Glutaminase Inhibitor Drug Discovery and Nanoparticle-Based Delivery for Pancreatic Cancer TherapyR01CA193895 · NCI · JOHNS HOPKINS UNIVERSITY · PI HANES, JUSTIN S., LE, ANNE · 2016 to 2020
$2.1M
Novel brain penetrant metabolic inhibitors to treat MYC-driven medulloblastomaR01NS103927 · NINDS · JOHNS HOPKINS UNIVERSITY · PI RAABE, ERIC HUTTON, SLUSHER, BARBARA STAUCH · 2018 to 2021
$1.6M
NCI NIH HHS R01 CA193895NCI NIH HHS R01 CA229451NINDS NIH HHS R01 NS103927
6 · The paper itself

Abstract

The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) exhibits remarkable anticancer efficacy; however, its therapeutic potential is hindered by its toxicity to gastrointestinal (GI) tissues. We recently reported the discovery of DRP-104, a tumor-targeted DON prodrug with excellent efficacy and tolerability, which is currently in clinical trials. However, DRP-104 exhibits limited aqueous solubility, and the instability of its isopropyl ester promoiety leads to the formation of an inactive M1-metabolite, reducing overall systemic prodrug exposure. Herein, we aimed to synthesize DON prodrugs with various ester and amide promoieties with improved solubility, GI stability, and DON tumor delivery. Twenty-one prodrugs were synthesized and characterized in stability and pharmacokinetics studies. Of these,

Indexed as

AcetamidesIndolesNeoplasmsProdrugsDiazooxonorleucineEstersGlutamineHumansAcetamidesDiazooxonorleucineEstersGlutamineIndolesProdrugssirpiglenastat

Identifiers

PMID37949450
PMCPMC10683027
OpenAlexW4388583015

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.