Evidence map›Paper›PMID 38927128›Full record

ArticleBiomolecules2024

Preclinical Evaluation of a Novel Series of Polyfluorinated Thalidomide Analogs in Drug-Resistant Multiple Myeloma.

Blaire E Barton, Matthew K Collins, Cindy H Chau, Hyoyoung Choo-Wosoba, David J Venzon, Christian Steinebach, Kathleen M Garchitorena, Bhruga Shah, Eric L Sarin, Michael Gütschow and 1 more

Abstract read
In one paragraph

Article in Biomolecules, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

11 authors.

Blaire E BartonMolecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-9421-8224
Matthew K CollinsMolecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-9305-3560
Cindy H ChauMolecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-6928-3833
Hyoyoung Choo-WosobaBiostatics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
David J VenzonBiostatics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-8990-158X
Christian SteinebachPharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, 53121 Bonn, Germany.ORCID 0000-0001-5638-1955
Kathleen M GarchitorenaMolecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0003-4461-1164
Bhruga ShahInova Heart and Vascular Institute, Inova Health System, Falls Church, VA 22042, USA.
Eric L SarinInova Heart and Vascular Institute, Inova Health System, Falls Church, VA 22042, USA.
Michael GütschowPharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, 53121 Bonn, Germany.ORCID 0000-0002-9376-7897
William D FiggMolecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0003-2428-5613

Funding

Development of Anticancer AgentsZIASC006538 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI FIGG, WILLIAM DOUGLAS · 2009 to 2025
$8.6M
German Research Foundation GRK2873 (49483089)NIH HHS ZIA BC 006538
6 · The paper itself

Abstract

Immunomodulatory imide drugs (IMiDs) play a crucial role in the treatment landscape across various stages of multiple myeloma. Despite their evident efficacy, some patients may exhibit primary resistance to IMiD therapy, and acquired resistance commonly arises over time leading to inevitable relapse. It is critical to develop novel therapeutic options to add to the treatment arsenal to overcome IMiD resistance. We designed, synthesized, and screened a new class of polyfluorinated thalidomide analogs and investigated their anti-cancer, anti-angiogenic, and anti-inflammatory activity using in vitro and ex vivo biological assays. We identified four lead compounds that exhibit potent anti-myeloma, anti-angiogenic, anti-inflammatory properties using three-dimensional tumor spheroid models, in vitro tube formation, and ex vivo human saphenous vein angiogenesis assays, as well as the THP-1 inflammatory assay. Western blot analyses investigating the expression of proteins downstream of cereblon (CRBN) reveal that Gu1215, our primary lead candidate, exerts its activity through a CRBN-independent mechanism. Our findings demonstrate that the lead compound Gu1215 is a promising candidate for further preclinical development to overcome intrinsic and acquired IMiD resistance in multiple myeloma.

Indexed as

Drug Resistance, NeoplasmMultiple MyelomaThalidomideAngiogenesis InhibitorsAnti-Inflammatory AgentsAntineoplastic AgentsCell Line, TumorDrug Evaluation, PreclinicalHumansAngiogenesis InhibitorsAnti-Inflammatory AgentsAntineoplastic AgentsThalidomideangiogenesiscereblonimmunomodulatory drugsmultiple myelomaresistance

Identifiers

PMID38927128
PMCPMC11201495

What OpenQuestion holds

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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.