Evidence map›Paper›PMID 24461291›Full record

ArticleBioorganic & medicinal chemistry letters2014

Undesired versus designed enzymatic cleavage of linkers for liver targeting.

Srinivas R Chirapu, Jonathan N Bauman, Heather Eng, Theunis C Goosen, Timothy J Strelevitz, Subhash C Sinha, Robert L Dow, M G Finn

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Srinivas R ChirapuDepartment of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
Jonathan N BaumanPfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA.
Heather EngPfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA.
Theunis C GoosenPfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA.
Timothy J StrelevitzPfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA.
Subhash C SinhaDepartment of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
Robert L DowPfizer Global Research & Development, 620 Memorial Drive, Cambridge, MA 02139, USA. Electronic address: robert.l.dow@pfizer.com.
M G FinnDepartment of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA. Electronic address: mgfinn@gatech.edu.

Funding

Project 9P50GM103368 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI TORBETT, BRUCE EDWARD · 2012 to 2016
$20.0M
NIGMS NIH HHS P50 GM103368
6 · The paper itself

Abstract

A design for the selective release of drug molecules in the liver was tested, involving the attachment of a representative active agent by an ester linkage to various 2-substituted 5-aminovaleric acid carbamates. The anticipated pathway of carboxylesterase-1-mediated carbamate cleavage followed by lactamization and drug release was frustrated by unexpectedly high sensitivity of the ester linkage toward hydrolysis by carboxylesterase-2 and other microsomal components.

Indexed as

Drug DesignAmino Acids, NeutralCarbamatesCarboxylesteraseCarboxylic Ester HydrolasesDose-Response Relationship, DrugHumansLiverMolecular StructureStructure-Activity Relationship5-aminovaleric acidAmino Acids, NeutralCarbamatesCarboxylesteraseCarboxylic Ester HydrolasesCES1 protein, humanCES2 protein, humanCarboxylesteraseCleavable linkersDrug targetingLiver targeting

Identifiers

PMID24461291
PMCPMC4319531

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.