Evidence map›Paper›PMID 24870016›Full record

ArticleJournal of biomolecular screening2014

Ultra-High-Throughput Screening of Natural Product Extracts to Identify Proapoptotic Inhibitors of Bcl-2 Family Proteins.

Christian A Hassig, Fu-Yue Zeng, Paul Kung, Mehrak Kiankarimi, Sylvia Kim, Paul W Diaz, Dayong Zhai, Kate Welsh, Shana Morshedian, Ying Su and 16 more

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

Article in Journal of biomolecular screening, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

12 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Investigating Andrographis paniculata Compounds for Apoptosis Induction in Cancer.Asian Pacific journal of cancer prevention : APJCP · 2025
    Article
  3. Review
  4. A nontoxic fungal natural product modulates fin regeneration in zebrafish larvae upstream of FGF-WNT developmental signaling.Developmental dynamics : an official publication of the American Association of Anatomists · 2021
    Article
  5. Problems that Can Occur when Assaying Extracts to Pure Compounds in Biological Systems.Current therapeutic research, clinical and experimental · 2021
    Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. 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

26 authors at 4 institutions in 1 country.

Christian A HassigSanford Burnham Medical Research Institute, La Jolla, CA, USA chassig@sanfordburnham.org.
Fu-Yue ZengSanford Burnham Medical Research Institute, La Jolla, CA, USA.
Paul KungSanford Burnham Medical Research Institute, La Jolla, CA, USA.
Mehrak KiankarimiSanford Burnham Medical Research Institute, La Jolla, CA, USA.
Sylvia KimSanford Burnham Medical Research Institute, La Jolla, CA, USA.
Paul W DiazSanford Burnham Medical Research Institute, La Jolla, CA, USA.
Dayong ZhaiSanford Burnham Medical Research Institute, La Jolla, CA, USA.
Kate WelshSanford Burnham Medical Research Institute, La Jolla, CA, USA.
Shana MorshedianSanford Burnham Medical Research Institute, La Jolla, CA, USA.
Ying SuSanford Burnham Medical Research Institute, La Jolla, CA, USA.
Barry O'KeefeNational Cancer Institute, Frederick, MD, USA.
David J NewmanNational Cancer Institute, Frederick, MD, USA.
Yudi RusmanCenter for Drug Design, University of Minnesota, Minneapolis, MN, USA.
Harneet KaurCenter for Drug Design, University of Minnesota, Minneapolis, MN, USA.
Christine E SalomonCenter for Drug Design, University of Minnesota, Minneapolis, MN, USA.
Susan G BrownDepartment of Chemistry, University of Minnesota, Minneapolis, MN, USA.
Beeraiah BaireDepartment of Chemistry, University of Minnesota, Minneapolis, MN, USA.
Andrew R MichelDepartment of Chemistry, University of Minnesota, Minneapolis, MN, USA.
Thomas R HoyeDepartment of Chemistry, University of Minnesota, Minneapolis, MN, USA.
Subhashree FrancisInstitute for Therapeutics Discovery and Development, Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA.
Gunda I GeorgInstitute for Therapeutics Discovery and Development, Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA.
Michael A WaltersInstitute for Therapeutics Discovery and Development, Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA.
Daniela B DivlianskaSanford-Burnham Medical Research Institute at Lake Nona, Orlando, FL, USA.
Gregory P RothSanford-Burnham Medical Research Institute at Lake Nona, Orlando, FL, USA.
Amy E WrightHarbor Branch Oceanographic Institute at Florida Atlantic University, Fort Pierce, FL, USA.
John C ReedSanford Burnham Medical Research Institute, La Jolla, CA, USA Roche Pharmaceuticals, Basel, Switzerland.
Sanford Burnham Prebys Medical Discovery Institute · USUniversity of Minnesota · USNational Cancer Institute · USHarbor Branch Oceanographic Institute · US

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
Cell-free assay technologies for the identification of active compoundsZIABC011471 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI OKEEFE, BARRY · 2012 to 2025
$12.4M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS Z99 CA999999NCI NIH HHS HHSN261200800001ENCI NIH HHS P30 CA030199
6 · The paper itself

Abstract

Antiapoptotic Bcl-2 family proteins are validated cancer targets composed of six related proteins. From a drug discovery perspective, these are challenging targets that exert their cellular functions through protein-protein interactions (PPIs). Although several isoform-selective inhibitors have been developed using structure-based design or high-throughput screening (HTS) of synthetic chemical libraries, no large-scale screen of natural product collections has been reported. A competitive displacement fluorescence polarization (FP) screen of nearly 150,000 natural product extracts was conducted against all six antiapoptotic Bcl-2 family proteins using fluorochrome-conjugated peptide ligands that mimic functionally relevant PPIs. The screens were conducted in 1536-well format and displayed satisfactory overall HTS statistics, with Z'-factor values ranging from 0.72 to 0.83 and a hit confirmation rate between 16% and 64%. Confirmed active extracts were orthogonally tested in a luminescent assay for caspase-3/7 activation in tumor cells. Active extracts were resupplied, and effort toward the isolation of pure active components was initiated through iterative bioassay-guided fractionation. Several previously described altertoxins were isolated from a microbial source, and the pure compounds demonstrate activity in both Bcl-2 FP and caspase cellular assays. The studies demonstrate the feasibility of ultra-high-throughput screening using natural product sources and highlight some of the challenges associated with this approach.

Indexed as

bcl-X ProteinBiological ProductsCaco-2 CellsCaspase 3Caspase 7Drug Screening Assays, AntitumorFluorescence PolarizationHigh-Throughput Screening AssaysHumansMiniaturizationMolecular Targeted TherapyMycotoxinsProto-Oncogene Proteins c-bcl-2Solid Phase Extractionbcl-X ProteinBiological ProductsCaspase 3Caspase 7MycotoxinsProto-Oncogene Proteins c-bcl-2apoptosisBcl-2 familybioassay-guided fractionationfluorescence polarizationnatural product extractsultra-high-throughput screening

Identifiers

PMID24870016
PMCPMC4521994
OpenAlexW1987812591

What OpenQuestion holds

Textmetadata
LicenceTDM
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.