Evidence map›Paper›PMID 26105954›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2015

Antitumor Activity of a Novel Sphingosine-1-Phosphate 2 Antagonist, AB1, in Neuroblastoma.

Mei-Hong Li, Rolf Swenson, Miriam Harel, Sampa Jana, Erik Stolarzewicz, Timothy Hla, Linda H Shapiro, Fernando Ferrer

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

Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

18 citing papers in PubMed, 26 citations in OpenAlex.

  1. Lipids: Driving Forces in the Underlying Biology of Carcinogenesis.ACS pharmacology & translational science · 2025
    Review
  2. Therapeutic Potential of Ceramide in Cancer Treatment.Journal of cancer research and oncobiology · 2024
    Article
  3. Targeting the myeloid microenvironment in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2023
    Review
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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

8 authors at 1 institution in 1 country.

Mei-Hong LiCenter for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut (M.-H.L., L.H.S., F.F.); Arroyo Biosciences, LLC, Princeton, New Jersey (R.S.); Department of Urology and Surgery, Connecticut Children's Medical Center, Hartford, Connecticut (M.H., F.F.); TCG Life Sciences Limited, Hinjewadi, Pune, India (S.J.); Chem-Master International Inc., Stony Brook, New York (E.S.); and Department of Pathology and Laboratory Medicine, Center for Vascular Biology, Weill Medical College of Cornell University, New York, New York (T.H.).
Rolf SwensonCenter for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut (M.-H.L., L.H.S., F.F.); Arroyo Biosciences, LLC, Princeton, New Jersey (R.S.); Department of Urology and Surgery, Connecticut Children's Medical Center, Hartford, Connecticut (M.H., F.F.); TCG Life Sciences Limited, Hinjewadi, Pune, India (S.J.); Chem-Master International Inc., Stony Brook, New York (E.S.); and Department of Pathology and Laboratory Medicine, Center for Vascular Biology, Weill Medical College of Cornell University, New York, New York (T.H.).
Miriam HarelCenter for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut (M.-H.L., L.H.S., F.F.); Arroyo Biosciences, LLC, Princeton, New Jersey (R.S.); Department of Urology and Surgery, Connecticut Children's Medical Center, Hartford, Connecticut (M.H., F.F.); TCG Life Sciences Limited, Hinjewadi, Pune, India (S.J.); Chem-Master International Inc., Stony Brook, New York (E.S.); and Department of Pathology and Laboratory Medicine, Center for Vascular Biology, Weill Medical College of Cornell University, New York, New York (T.H.).
Sampa JanaCenter for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut (M.-H.L., L.H.S., F.F.); Arroyo Biosciences, LLC, Princeton, New Jersey (R.S.); Department of Urology and Surgery, Connecticut Children's Medical Center, Hartford, Connecticut (M.H., F.F.); TCG Life Sciences Limited, Hinjewadi, Pune, India (S.J.); Chem-Master International Inc., Stony Brook, New York (E.S.); and Department of Pathology and Laboratory Medicine, Center for Vascular Biology, Weill Medical College of Cornell University, New York, New York (T.H.).
Erik StolarzewiczCenter for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut (M.-H.L., L.H.S., F.F.); Arroyo Biosciences, LLC, Princeton, New Jersey (R.S.); Department of Urology and Surgery, Connecticut Children's Medical Center, Hartford, Connecticut (M.H., F.F.); TCG Life Sciences Limited, Hinjewadi, Pune, India (S.J.); Chem-Master International Inc., Stony Brook, New York (E.S.); and Department of Pathology and Laboratory Medicine, Center for Vascular Biology, Weill Medical College of Cornell University, New York, New York (T.H.).
Timothy HlaCenter for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut (M.-H.L., L.H.S., F.F.); Arroyo Biosciences, LLC, Princeton, New Jersey (R.S.); Department of Urology and Surgery, Connecticut Children's Medical Center, Hartford, Connecticut (M.H., F.F.); TCG Life Sciences Limited, Hinjewadi, Pune, India (S.J.); Chem-Master International Inc., Stony Brook, New York (E.S.); and Department of Pathology and Laboratory Medicine, Center for Vascular Biology, Weill Medical College of Cornell University, New York, New York (T.H.).
Linda H ShapiroCenter for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut (M.-H.L., L.H.S., F.F.); Arroyo Biosciences, LLC, Princeton, New Jersey (R.S.); Department of Urology and Surgery, Connecticut Children's Medical Center, Hartford, Connecticut (M.H., F.F.); TCG Life Sciences Limited, Hinjewadi, Pune, India (S.J.); Chem-Master International Inc., Stony Brook, New York (E.S.); and Department of Pathology and Laboratory Medicine, Center for Vascular Biology, Weill Medical College of Cornell University, New York, New York (T.H.).
Fernando FerrerCenter for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut (M.-H.L., L.H.S., F.F.); Arroyo Biosciences, LLC, Princeton, New Jersey (R.S.); Department of Urology and Surgery, Connecticut Children's Medical Center, Hartford, Connecticut (M.H., F.F.); TCG Life Sciences Limited, Hinjewadi, Pune, India (S.J.); Chem-Master International Inc., Stony Brook, New York (E.S.); and Department of Pathology and Laboratory Medicine, Center for Vascular Biology, Weill Medical College of Cornell University, New York, New York (T.H.) fferrer@connecticutchildrens.org.
Cornell University · US

Funding

THE ROLE OF ENDOCANNABINOIDS AND THEIR RECEPTORS IN COLORECTAL CANCERP01CA077839 · NCI · VANDERBILT UNIVERSITY · PI DUBOIS, RAYMOND N. · 1999 to 2016
$17.8M
Sphingosine-1-Phosphate Pathway Based Therapy for NeuroblastomaR01CA168903 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI FERRER, FERNANDO A, SHAPIRO, LINDA H · 2012 to 2016
$1.7M
NCI NIH HHS P01 CA077839NCI NIH HHS P01-CA77839NCI NIH HHS R01 CA168903NCI NIH HHS R01-CA168903
6 · The paper itself

Abstract

The bioactive lipid sphingosine-1-phosphate (S1P) and its receptors (S1P1-5) play critical roles in many pathologic processes, including cancer. The S1P axis has become a bona fide therapeutic target in cancer. JTE-013 [N-​(2,​6-​dichloro-​4-​pyridinyl)-​2-​[1,​3-​dimethyl-​4-​(1-​methylethyl)-​1H-​pyrazolo[3,​4-​b]pyridin-​6-​yl]-​hydrazinecarboxamide], a known S1P2 antagonist, suffers from instability in vivo. Structurally modified, more potent, and stable S1P2 inhibitors would be desirable pharmacological tools. One of the JTE-013 derivatives, AB1 [N-(1H-4-isopropyl-1-allyl-3-methylpyrazolo[3,4-b]pyridine-6-yl)-amino-N'-(2,6-dichloropyridine-4-yl) urea], exhibited improved S1P2 antagonism compared with JTE-013. Intravenous pharmacokinetics indicated enhanced stability or slower clearance of AB1 in vivo. Migration assays in glioblastoma showed that AB1 was slightly more effective than JTE-013 in blocking S1P2-mediated inhibition of cell migration. Functional studies in the neuroblastoma (NB) cell line SK-N-AS showed that AB1 displayed potency at least equivalent to JTE-013 in affecting signaling molecules downstream of S1P2. Similarly, AB1 inhibition of the growth of SK-N-AS tumor xenografts was improved compared with JTE-013. Cell viability assays excluded that this enhanced AB1 effect is caused by inhibition of cancer cell survival. Both JTE-013 and AB1 trended to inhibit (C-C motif) ligand 2 expression and were able to significantly inhibit subsequent tumor-associated macrophage infiltration in NB xenografts. Interestingly, AB1 was more effective than JTE-013 in inhibiting the expression of the profibrotic mediator connective tissue growth factor. The terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling assay and cleaved caspase-3 detection further demonstrated that apoptosis was increased in AB1-treated NB xenografts compared with JTE-013. Overall, the modification of JTE-013 to produce the AB1 compound improved potency, intravenous pharmacokinetics, cellular activity, and antitumor activity in NB and may have enhanced clinical and experimental applicability.

Indexed as

AnimalsAntineoplastic AgentsCaspase 3Cell Line, TumorCell MovementCell SurvivalChlorambucilConnective Tissue Growth FactorFemaleHeterograftsHumansMiceMice, NudeNeuroblastomaPyrazolesPyridinesAntineoplastic AgentsCaspase 3Chlorambucilchlorambucil-N-(2-(4-(4-bis(2-chloroethyl)aminophenyl)butyryl)aminoethyl)-5-(4-amidinophenyl)-2-furancarboxamide hydrochlorideConnective Tissue Growth FactorJTE 013PyrazolesPyridinesReceptors, LysosphingolipidS1PR2 protein, humanSphingosine-1-Phosphate Receptors

Identifiers

PMID26105954
PMCPMC4538871
OpenAlexW1922594443

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.