Evidence map›Paper›PMID 28038940›Full record

ArticleBioorganic & medicinal chemistry2017

Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors.

Li Tan, Deepak Gurbani, Ellen L Weisberg, Douglas S Jones, Suman Rao, William D Singer, Faviola M Bernard, Samar Mowafy, Annie Jenney, Guangyan Du and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

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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

16 authors.

Li TanDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA.
Deepak GurbaniDepartment of Biochemistry, The University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
Ellen L WeisbergDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Douglas S JonesHMS LINCS Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02215, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Suman RaoDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA; HMS LINCS Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02215, USA.
William D SingerDepartment of Biochemistry, The University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA; Department of Radiation Oncology, The University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
Faviola M BernardDepartment of Biochemistry, The University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA; Department of Radiation Oncology, The University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
Samar MowafyDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA; Misr International University, Km 28 Cairo, Ismailia Rd., Ahmed Orabi Dist., Cairo, Egypt.
Annie JenneyHMS LINCS Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02215, USA.
Guangyan DuDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA.
Atsushi NonamiDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
James D GriffinDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Douglas A LauffenburgerDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Kenneth D WestoverDepartment of Biochemistry, The University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA; Department of Radiation Oncology, The University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. Electronic address: Kenneth.Westover@UTSouthwestern.edu.
Peter K SorgerHMS LINCS Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02215, USA. Electronic address: Peter_Sorger@hms.harvard.edu.
Nathanael S GrayDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA. Electronic address: Nathanael_Gray@dfci.harvard.edu.

Funding

StructureP01CA154303 · NCI · DANA-FARBER CANCER INST · PI JANNE, PASI A · 2012 to 2021
$17.8M
Pharmaco Response Signatures and Disease MechanismU54HL127365 · NHLBI · HARVARD MEDICAL SCHOOL · PI SORGER, PETER KARL · 2014 to 2019
$13.1M
TRANSLATIONAL PHARMACOLOGY COREP50GM107618 · NIGMS · HARVARD MEDICAL SCHOOL · PI MALISZEWSKI, LAURA ELIZABETH · 2014 to 2018
$10.8M
NCI NIH HHS P01 CA154303NHLBI NIH HHS U54 HL127365NIGMS NIH HHS P50 GM107618
6 · The paper itself

Abstract

Targeted polypharmacology provides an efficient method of treating diseases such as cancer with complex, multigenic causes provided that compounds with advantageous activity profiles can be discovered. Novel covalent TAK1 inhibitors were validated in cellular contexts for their ability to inhibit the TAK1 kinase and for their polypharmacology. Several inhibitors phenocopied reported TAK1 inhibitor 5Z-7-oxozaenol with comparable efficacy and complementary kinase selectivity profiles. Compound 5 exhibited the greatest potency in RAS-mutated and wild-type RAS cell lines from various cancer types. A biotinylated derivative of 5, 27, was used to verify TAK1 binding in cells. The newly described inhibitors constitute useful tools for further development of multi-targeting TAK1-centered inhibitors for cancer and other diseases.

Indexed as

Cell Line, TumorCell ProliferationCell SurvivalCytokinesDose-Response Relationship, DrugHumansMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMolecular StructureProtein Kinase InhibitorsStructure-Activity RelationshipCytokinesMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesProtein Kinase InhibitorsCancerCytokine secretionMultitargetPolypharmacologyTAK1

Identifiers

PMID28038940
PMCPMC5484535

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.