Evidence map›Paper›PMID 26013543›Full record

ArticleMolecular pharmacology2015

Structural Basis of Species-Dependent Differential Affinity of 6-Alkoxy-5-Aryl-3-Pyridinecarboxamide Cannabinoid-1 Receptor Antagonists.

Malliga R Iyer, Resat Cinar, Jie Liu, Grzegorz Godlewski, Gergö Szanda, Henry Puhl, Stephen R Ikeda, Jeffrey Deschamps, Yong-Sok Lee, Peter J Steinbach and 1 more

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

Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

9 citing papers in PubMed, 18 citations in OpenAlex.

  1. Pharmacological Evaluation of Cannabinoid Receptor Modulators Using GRABInternational journal of molecular sciences · 2024
    Article
  2. Article
  3. Peripheral Hybrid CBFrontiers in endocrinology · 2021
    Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
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

11 authors at 4 institutions in 1 country.

Malliga R IyerLaboratory of Physiologic Studies (M.R.I., R.C., J.L., G.G., G.S., G.K.) and Laboratory of Molecular Physiology (H.P., S.R.I.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Naval Research Laboratory, Washington, D.C. (J.D.); and Center for Molecular Modeling, Center for Information Technology, National Institutes of Health, Bethesda, Maryland (Y.-S.L., P.J.S.).
Resat CinarLaboratory of Physiologic Studies (M.R.I., R.C., J.L., G.G., G.S., G.K.) and Laboratory of Molecular Physiology (H.P., S.R.I.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Naval Research Laboratory, Washington, D.C. (J.D.); and Center for Molecular Modeling, Center for Information Technology, National Institutes of Health, Bethesda, Maryland (Y.-S.L., P.J.S.).
Jie LiuLaboratory of Physiologic Studies (M.R.I., R.C., J.L., G.G., G.S., G.K.) and Laboratory of Molecular Physiology (H.P., S.R.I.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Naval Research Laboratory, Washington, D.C. (J.D.); and Center for Molecular Modeling, Center for Information Technology, National Institutes of Health, Bethesda, Maryland (Y.-S.L., P.J.S.).
Grzegorz GodlewskiLaboratory of Physiologic Studies (M.R.I., R.C., J.L., G.G., G.S., G.K.) and Laboratory of Molecular Physiology (H.P., S.R.I.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Naval Research Laboratory, Washington, D.C. (J.D.); and Center for Molecular Modeling, Center for Information Technology, National Institutes of Health, Bethesda, Maryland (Y.-S.L., P.J.S.).
Gergö SzandaLaboratory of Physiologic Studies (M.R.I., R.C., J.L., G.G., G.S., G.K.) and Laboratory of Molecular Physiology (H.P., S.R.I.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Naval Research Laboratory, Washington, D.C. (J.D.); and Center for Molecular Modeling, Center for Information Technology, National Institutes of Health, Bethesda, Maryland (Y.-S.L., P.J.S.).
Henry PuhlLaboratory of Physiologic Studies (M.R.I., R.C., J.L., G.G., G.S., G.K.) and Laboratory of Molecular Physiology (H.P., S.R.I.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Naval Research Laboratory, Washington, D.C. (J.D.); and Center for Molecular Modeling, Center for Information Technology, National Institutes of Health, Bethesda, Maryland (Y.-S.L., P.J.S.).
Stephen R IkedaLaboratory of Physiologic Studies (M.R.I., R.C., J.L., G.G., G.S., G.K.) and Laboratory of Molecular Physiology (H.P., S.R.I.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Naval Research Laboratory, Washington, D.C. (J.D.); and Center for Molecular Modeling, Center for Information Technology, National Institutes of Health, Bethesda, Maryland (Y.-S.L., P.J.S.).
Jeffrey DeschampsLaboratory of Physiologic Studies (M.R.I., R.C., J.L., G.G., G.S., G.K.) and Laboratory of Molecular Physiology (H.P., S.R.I.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Naval Research Laboratory, Washington, D.C. (J.D.); and Center for Molecular Modeling, Center for Information Technology, National Institutes of Health, Bethesda, Maryland (Y.-S.L., P.J.S.).
Yong-Sok LeeLaboratory of Physiologic Studies (M.R.I., R.C., J.L., G.G., G.S., G.K.) and Laboratory of Molecular Physiology (H.P., S.R.I.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Naval Research Laboratory, Washington, D.C. (J.D.); and Center for Molecular Modeling, Center for Information Technology, National Institutes of Health, Bethesda, Maryland (Y.-S.L., P.J.S.).
Peter J SteinbachLaboratory of Physiologic Studies (M.R.I., R.C., J.L., G.G., G.S., G.K.) and Laboratory of Molecular Physiology (H.P., S.R.I.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Naval Research Laboratory, Washington, D.C. (J.D.); and Center for Molecular Modeling, Center for Information Technology, National Institutes of Health, Bethesda, Maryland (Y.-S.L., P.J.S.).
George KunosLaboratory of Physiologic Studies (M.R.I., R.C., J.L., G.G., G.S., G.K.) and Laboratory of Molecular Physiology (H.P., S.R.I.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Naval Research Laboratory, Washington, D.C. (J.D.); and Center for Molecular Modeling, Center for Information Technology, National Institutes of Health, Bethesda, Maryland (Y.-S.L., P.J.S.) george.kunos@nih.gov.
National Institutes of Health · USUnited States Naval Research Laboratory · USCenter for Information Technology · USNational Institute on Alcohol Abuse and Alcoholism · US

Funding

Endocannabinoids And Energy HomeostasisZIAAA000350 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI KUNOS, GEORGE · 2009 to 2025
$28.4M
Neuronal Ion Channel Modulation By Second MessengersZIAAA000430 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI IKEDA, STEPHEN R · 2009 to 2017
$13.7M
Simulating Protein Structures, Complexes, And DynamicsZIACT000265 · CIT · CENTER FOR INFORMATION TECHNOLOGY · PI STEINBACH, PETER J · 2009 to 2020
$8.2M
BRIDGING THE DISCONNECTN01DA001101 · NIDA · MANAGEMENT ASSISTANCE CORPORATION · PI FISCHER, GLENN · 2000 to 2000
$322k
NIDA NIH HHS Y1-DA1101
6 · The paper itself

Abstract

6-Alkoxy-5-aryl-3-pyridincarboxamides, including the brain-penetrant compound 14G: [5-(4-chlorophenyl)-6-(cyclopropylmethoxy)-N-[(1R,2R)-2-hydroxy-cyclohexyl]-3-pyridinecarboxamide] and its peripherally restricted analog 14H: [5-(4-chlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-6-(2-methoxyethoxy)-3-pyridinecarboxamide], have been recently introduced as selective, high-affinity antagonists of the human cannabinoid-1 receptor (hCB1R). Binding analyses revealed two orders of magnitude lower affinity of these compounds for mouse and rat versus human CB1R, whereas the affinity of rimonabant is comparable for all three CB1Rs. Modeling of ligand binding to CB1R and binding assays with native and mutant (Ile105Met) hCB1Rs indicate that the Ile105 to Met mutation in rodent CB1Rs accounts for the species-dependent affinity of 14G: and 14H: . Our work identifies Ile105 as a new pharmacophore component for developing better hCB1R antagonists and invalidates rodent models for assessing the antiobesity efficacy of 14G: and 14H: .

Indexed as

AnimalsBrainCannabinoid Receptor AntagonistsHEK293 CellsHumansIsoleucineMiceModels, MolecularNiacinamidePiperidinesPyrazolesRatsReceptor, Cannabinoid, CB1RimonabantSpecies SpecificityStructure-Activity Relationship5-(4-chlorophenyl)-6-(cyclopropylmethoxy)-N-(2-hydroxycyclohexyl)-3-pyridinecarboxamide5-(4-chlorophenyl)-N-(2-hydroxycyclohexyl)-6-(2-methoxyethoxy)-3-pyridinecarboxamideCannabinoid Receptor AntagonistsCNR1 protein, humanCNR1 protein, mouseIsoleucineNiacinamidePiperidinesPyrazolesReceptor, Cannabinoid, CB1Rimonabant

Identifiers

PMID26013543
PMCPMC4518088
OpenAlexW2120720610

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.