Evidence map›Paper›PMID 30446439›Full record

ArticleBioorganic & medicinal chemistry2019

Synthesis and evaluation of potent and selective MGL inhibitors as a glaucoma treatment.

Shakiru O Alapafuja, Michael S Malamas, Vidyanand Shukla, Alexander Zvonok, Sally Miller, Laura Daily, Girija Rajarshi, Christina Yume Miyabe, Honrao Chandrashekhar, JodiAnne Wood and 3 more

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

Article in Bioorganic & medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 28% 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

2 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Role of Endocannabinoids in Glaucoma: A Review.Journal of current glaucoma practice
    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

13 authors at 3 institutions in 1 country.

Shakiru O AlapafujaMAK Scientific LLC, 151 South Bedford Street, Burlington, MA 01803 USA.
Michael S MalamasCenter for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA. Electronic address: m.malamas@northeastern.edu.
Vidyanand ShuklaCenter for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Alexander ZvonokCenter for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Sally MillerDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Laura DailyDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Girija RajarshiCenter for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Christina Yume MiyabeCenter for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Honrao ChandrashekharCenter for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
JodiAnne WoodCenter for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Sergiy TyukhtenkoCenter for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Alex StraikerDepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Alexandros MakriyannisCenter for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Northeastern University · USIndiana University Bloomington · USBoston Scientific (United States) · US

Funding

MOLECULAR BASIS OF CANNABINOID ACTIVITYR01DA003801 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI MAKRIYANNIS, ALEXANDROS · 1985 to 2017
$2.5M
Harnessing endogenous cannabinoids for ocular healthR01EY024625 · NEI · TRUSTEES OF INDIANA UNIVERSITY · PI STRAIKER, ALEXANDER J · 2014 to 2017
$1.3M
NEI NIH HHS R01 EY024625NIDA NIH HHS R01 DA003801
6 · The paper itself

Abstract

Monoacylglycerol lipase (MGL) inhibition provides a potential treatment approach to glaucoma through the regulation of ocular 2-arachidonoylglycerol (2-AG) levels and the activation of CB1 receptors. Herein, we report the discovery of new series of carbamates as highly potent and selective MGL inhibitors. The new inhibitors showed potent nanomolar inhibitory activity against recombinant human and purified rat MGL, were selective (>1000-fold) against serine hydrolases FAAH and ABHD6 and lacked any affinity for the cannabinoid receptors CB1 and CB2. Protein-based

Indexed as

AnimalsCarbamatesCatalytic DomainEnzyme InhibitorsGlaucomaHumansMaleMice, Inbred C57BLMicrosomes, LiverMolecular Docking SimulationMolecular StructureMonoacylglycerol LipasesPiperazinesPiperidinesRatsStructure-Activity RelationshipCarbamatesEnzyme InhibitorsMonoacylglycerol LipasesPiperazinesPiperidines2-Arachidonoylglycerol (2-AG)Anandamide (AEA)CB1CB2 cannabinoid receptorsFatty acid amide hydrolase (FAAH)GlaucomaMonoacylglycerol lipase (MGL)N-arachidonoylethanolamide(−)-Δ(9)-tetrahydrocannabinolΔ(9)-THC

Identifiers

PMID30446439
PMCPMC8344409
OpenAlexW2898792152

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.