Evidence map›Paper›PMID 26088334›Full record

ArticleBioorganic & medicinal chemistry2015

Synthesis and antileukemic activities of C1-C10-modified parthenolide analogues.

Aaron M Kempema, John C Widen, Joseph K Hexum, Timothy E Andrews, Dan Wang, Susan K Rathe, Frederick A Meece, Klara E Noble, Zohar Sachs, David A Largaespada and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Crystal structure of 13-(Acta crystallographica. Section E, Crystallographic communications · 2018
    Article
  8. Article
  9. Article
  10. Article
  11. 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.

Aaron M KempemaDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
John C WidenDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
Joseph K HexumDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
Timothy E AndrewsDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
Dan WangDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
Susan K RatheMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Frederick A MeeceDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
Klara E NobleDivision of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Zohar SachsDivision of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
David A LargaespadaMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Daniel A HarkiDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: daharki@umn.edu.

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Jeffrey S. Miller · 1998 to 2026
$100.4M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR000114 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2012 to 2015
$35.0M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)KL2TR000113 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2012 to 2015
$5.4M
NCATS NIH HHS KL2 TR000113NCATS NIH HHS UL1 TR000114NCI NIH HHS P30 CA077598NCI NIH HHS P30 CA77598
6 · The paper itself

Abstract

Parthenolide (PTL) is a sesquiterpene lactone natural product with anti-proliferative activity to cancer cells. Selective eradication of leukemic stem cells (LSCs) over healthy hematopoietic stem cells (HSCs) by PTL has been demonstrated in previous studies, which suggests PTL and related molecules may be useful for targeting LSCs. Eradication of LSCs is required for curative therapy. Chemical optimizations of PTL to improve potency and pharmacokinetic parameters have focused largely on the α-methylene-γ-butyrolactone, which is essential for activity. Conversely, we evaluated modifications to the C1-C10 olefin and benchmarked new inhibitors to PTL with respect to inhibitory potency across a panel of cancer cell lines, ability to target drug-resistant acute myeloid leukemia (AML) cells, efficacy for inhibiting clonal growth of AML cells, toxicity to healthy bone marrow cells, and efficiency for promoting intracellular reactive oxygen species (ROS) levels. Cyclopropane 4 was found to possess less toxicity to healthy bone marrow cells, enhanced potency for the induction of cellular ROS, and similar broad-spectrum anti-proliferative activity to cancer cells in comparison to PTL.

Indexed as

AlkenesAnimalsAntineoplastic AgentsBone Marrow CellsCell Line, TumorCell SurvivalCrystallography, X-RayDrug DesignDrug Screening Assays, AntitumorHumansLeukemia, Myeloid, AcuteMiceMolecular ConformationNeoplastic Stem CellsReactive Oxygen SpeciesSesquiterpenesAlkenesAntineoplastic AgentsparthenolideReactive Oxygen SpeciesSesquiterpenesAcute myeloid leukemiaBone marrow toxicityCyclopropanationParthenolideSesquiterpene lactone

Identifiers

PMID26088334
PMCPMC4697833

What OpenQuestion holds

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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.