Evidence map›Paper›PMID 24900374›Full record

ArticleACS medicinal chemistry letters2012

Optimization of a Potent, Orally Active S1P1 Agonist Containing a Quinolinone Core.

Paul E Harrington, Michael D Croghan, Christopher Fotsch, Mike Frohn, Brian A Lanman, Lewis D Pennington, Alexander J Pickrell, Anthony B Reed, Kelvin K C Sham, Andrew Tasker and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS medicinal chemistry letters, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. An update on sphingosine-1-phosphate receptor 1 modulators.Bioorganic & medicinal chemistry letters · 2018
    Review
  3. Modulators of the Sphingosine 1-phosphate receptor 1.Bioorganic & medicinal chemistry letters · 2013
    Review
  4. Article
  5. 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

20 authors.

Paul E HarringtonChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Michael D CroghanChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Christopher FotschChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Mike FrohnChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Brian A LanmanChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Lewis D PenningtonChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Alexander J PickrellChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Anthony B ReedChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Kelvin K C ShamChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Andrew TaskerChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Heather A ArnettChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Michael FiorinoChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Matthew R LeeChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Michele McElvainChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Henry G MorrisonChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Han XuChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Yang XuChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Xuxia ZhangChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Min WongChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
Victor J CeeChemistry Research and Discovery, Inflammation Research, Molecular Structure, HTS and Molecular Pharmacology, Pharmaceutics, and Pharmacokinetics and Drug Metabolism, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The optimization of a series of S1P1 agonists with limited activity against S1P3 is reported. A polar headgroup was used to improve the physicochemical and pharmacokinetic parameters of lead quinolinone 6. When dosed orally at 1 and 3 mg/kg, the azahydroxymethyl analogue 22 achieved statistically significant lowering of circulating blood lymphocytes 24 h postdose. In rats, a dose-proportional increase in exposure was measured when 22 was dosed orally at 2 and 100 mg/kg.

Indexed as

agonistmultiple sclerosisS1P1Sphingosine-1-phosphate receptor

Identifiers

PMID24900374
PMCPMC4025730

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.