Evidence map›Paper›PMID 32591477›Full record

ArticleMolecular pharmacology2020

Structural Refinement of the Tubulin Ligand (+)-Discodermolide to Attenuate Chemotherapy-Mediated Senescence.

Boying Guo, Alicia Rodriguez-Gabin, Andrea E Prota, Tobias Mühlethaler, Nan Zhang, Kenny Ye, Michel O Steinmetz, Susan Band Horwitz, Amos B Smith, Hayley M McDaid

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

Article in Molecular pharmacology, 2020. 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
0.4field-weighted citation impact, top 42% 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, 6 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. 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

10 authors at 4 institutions in 2 countries.

Boying GuoDepartment of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania (B.G., N.Z., A.B.S.); Departments of Molecular Pharmacology (A.R.-G., S.B.H., H.M.M.), Epidemiology (K.Y.), and Medicine (H.M.M.), Albert Einstein College of Medicine, Bronx, New York; Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland (A.E.P., T.M., M.O.S.); and University of Basel, Biozentrum, Basel, Switzerland (M.O.S.).
Alicia Rodriguez-GabinDepartment of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania (B.G., N.Z., A.B.S.); Departments of Molecular Pharmacology (A.R.-G., S.B.H., H.M.M.), Epidemiology (K.Y.), and Medicine (H.M.M.), Albert Einstein College of Medicine, Bronx, New York; Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland (A.E.P., T.M., M.O.S.); and University of Basel, Biozentrum, Basel, Switzerland (M.O.S.).
Andrea E ProtaDepartment of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania (B.G., N.Z., A.B.S.); Departments of Molecular Pharmacology (A.R.-G., S.B.H., H.M.M.), Epidemiology (K.Y.), and Medicine (H.M.M.), Albert Einstein College of Medicine, Bronx, New York; Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland (A.E.P., T.M., M.O.S.); and University of Basel, Biozentrum, Basel, Switzerland (M.O.S.).
Tobias MühlethalerDepartment of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania (B.G., N.Z., A.B.S.); Departments of Molecular Pharmacology (A.R.-G., S.B.H., H.M.M.), Epidemiology (K.Y.), and Medicine (H.M.M.), Albert Einstein College of Medicine, Bronx, New York; Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland (A.E.P., T.M., M.O.S.); and University of Basel, Biozentrum, Basel, Switzerland (M.O.S.).
Nan ZhangDepartment of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania (B.G., N.Z., A.B.S.); Departments of Molecular Pharmacology (A.R.-G., S.B.H., H.M.M.), Epidemiology (K.Y.), and Medicine (H.M.M.), Albert Einstein College of Medicine, Bronx, New York; Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland (A.E.P., T.M., M.O.S.); and University of Basel, Biozentrum, Basel, Switzerland (M.O.S.).
Kenny YeDepartment of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania (B.G., N.Z., A.B.S.); Departments of Molecular Pharmacology (A.R.-G., S.B.H., H.M.M.), Epidemiology (K.Y.), and Medicine (H.M.M.), Albert Einstein College of Medicine, Bronx, New York; Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland (A.E.P., T.M., M.O.S.); and University of Basel, Biozentrum, Basel, Switzerland (M.O.S.).
Michel O SteinmetzDepartment of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania (B.G., N.Z., A.B.S.); Departments of Molecular Pharmacology (A.R.-G., S.B.H., H.M.M.), Epidemiology (K.Y.), and Medicine (H.M.M.), Albert Einstein College of Medicine, Bronx, New York; Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland (A.E.P., T.M., M.O.S.); and University of Basel, Biozentrum, Basel, Switzerland (M.O.S.).
Susan Band HorwitzDepartment of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania (B.G., N.Z., A.B.S.); Departments of Molecular Pharmacology (A.R.-G., S.B.H., H.M.M.), Epidemiology (K.Y.), and Medicine (H.M.M.), Albert Einstein College of Medicine, Bronx, New York; Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland (A.E.P., T.M., M.O.S.); and University of Basel, Biozentrum, Basel, Switzerland (M.O.S.).
Amos B SmithDepartment of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania (B.G., N.Z., A.B.S.); Departments of Molecular Pharmacology (A.R.-G., S.B.H., H.M.M.), Epidemiology (K.Y.), and Medicine (H.M.M.), Albert Einstein College of Medicine, Bronx, New York; Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland (A.E.P., T.M., M.O.S.); and University of Basel, Biozentrum, Basel, Switzerland (M.O.S.).
Hayley M McDaidDepartment of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania (B.G., N.Z., A.B.S.); Departments of Molecular Pharmacology (A.R.-G., S.B.H., H.M.M.), Epidemiology (K.Y.), and Medicine (H.M.M.), Albert Einstein College of Medicine, Bronx, New York; Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland (A.E.P., T.M., M.O.S.); and University of Basel, Biozentrum, Basel, Switzerland (M.O.S.) hayley.mcdaid@einsteinmed.org.
Paul Scherrer Institute · CHUniversity of Pennsylvania · USAlbert Einstein College of Medicine · USUniversity of Basel · CH

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI THOMAS E ROHAN · 1985 to 2026
$111.2M
TAXOL--MECHANISMS OF ACTION AND RESISTANCER01CA077263 · NCI · YESHIVA UNIVERSITY · PI HORWITZ, SUSAN BAND, MCDAID, HAYLEY M. · 1998 to 2019
$7.8M
NCI NIH HHS P30 CA013330NCI NIH HHS R01 CA077263
6 · The paper itself

Abstract

The natural product (+)-discodermolide (DDM) is a microtubule stabilizing agent and potent inducer of senescence. We refined the structure of DDM and evaluated the activity of novel congeners in triple negative breast and ovarian cancers, malignancies that typically succumb to taxane resistance. Previous structure-activity analyses identified the lactone and diene as moieties conferring anticancer activity, thus identifying priorities for the structural refinement studies described herein. Congeners possessing the monodiene with a simplified lactone had superior anticancer efficacy relative to taxol, particularly in resistant models. Specifically, one of these congeners, B2, demonstrated 1) improved pharmacologic properties, specifically increased maximum response achievable and area under the curve, and decreased EC

Indexed as

A549 CellsAlkanesArea Under CurveCarbamatesCell Line, TumorCell SurvivalCrystallography, X-RayDose-Response Relationship, DrugDrug Resistance, NeoplasmFemaleHumansLactonesMolecular StructureOvarian NeoplasmsPyronesTaxoidsAlkanesCarbamatesdiscodermolideLactonesPyronesTaxoidsTubulin Modulators

Identifiers

PMID32591477
PMCPMC7362599
OpenAlexW3037491670

What OpenQuestion holds

Textmetadata
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.