Evidence map›Paper›PMID 39492252›Full record

ArticleBioorganic & medicinal chemistry2023

Probing a distinct druggable tubulin binding site with gatorbulins 1-7, their metabolic and physicochemical properties, and pharmacological consequences.

Qi-Yin Chen, Ranjala Ratnayake, Rafael Hortigüela, Gustavo M Seabra, Michael D Cameron, J Fernando Díaz, María Ángela Oliva, Hendrik Luesch

Abstract read
In one paragraph

Article in Bioorganic & medicinal chemistry, 2023. 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
–field-weighted citation impact
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.

  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

8 authors.

Qi-Yin ChenDepartment of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, United States; Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL 32610, United States.
Ranjala RatnayakeDepartment of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, United States; Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL 32610, United States.
Rafael HortigüelaCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Gustavo M SeabraDepartment of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, United States; Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL 32610, United States.
Michael D CameronThe Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, 120 Scripps Way, Jupiter, FL 33458, United States.
J Fernando DíazCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, 28040 Madrid, Spain.
María Ángela OlivaCentro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Hendrik LueschDepartment of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, United States; Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL 32610, United States. Electronic address: luesch@cop.ufl.edu.

Funding

Novel Targeted Anticancer Agents from Marine CyanobacteriaR01CA172310 · NCI · UNIVERSITY OF FLORIDA · PI HENDRIK LUESCH · 2013 to 2026
$5.8M
NMR console upgrade for structural biology and metabolomicsS10OD028753 · OD · UNIVERSITY OF FLORIDA · PI LONG, JOANNA R · 2020 to 2020
$600k
NCI NIH HHS R01 CA172310NIH HHS S10 OD028753
6 · The paper itself

Abstract

Microtubules, consisting of α/β-tubulin heterodimers, are prime targets for anticancer drug discovery. Gatorbulin-1 (GB1, 1a) is a recently described marine natural product that targets tubulin at a new, seventh pharmacological site at the tubulin intradimer interface. Using our previously developed robust route towards GB1 (1a), we synthesized simplified, first-generation gatorbulins, GB2-7 (1b-1g) of this highly modified cyclodepsipeptide (GB1) that does not contain any proteinogenic amino acid. We systematically investigated the structure-activity relationship at the biochemical and cellular level using GB1-susceptible ovarian and cervical cancer cells. We validated that the hydroxamate moiety in the N-methyl-alanine residue is critical for activity. All other structural modifications present in GB1, including C-hydroxylation of asparagine, methylation at C-4 of proline, and sp

Indexed as

Anticancer drugsGatorbulinsTotal synthesisTubulin bindingTubulin polymerization inhibitors

Identifiers

PMID39492252
PMCPMC11995438

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Registered trials

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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.