Evidence map›Paper›PMID 27865404›Full record

ArticleTuberculosis (Edinburgh, Scotland)2016

Formulation studies of InhA inhibitors and combination therapy to improve efficacy against Mycobacterium tuberculosis.

Susan E Knudson, Jason E Cummings, Gopal R Bommineni, Pan Pan, Peter J Tonge, Richard A Slayden

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

Article in Tuberculosis (Edinburgh, Scotland), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.7field-weighted citation impact, top 26% 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

1 citing paper in PubMed, 5 citations in OpenAlex.

  1. 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

6 authors at 2 institutions in 1 country.

Susan E KnudsonDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
Jason E CummingsDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
Gopal R BommineniInstitute for Chemical Biology & Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, NY, USA.
Pan PanInstitute for Chemical Biology & Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, NY, USA.
Peter J TongeInstitute for Chemical Biology & Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, NY, USA.
Richard A SlaydenDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA. Electronic address: richard.slayden@colostate.edu.
Colorado State University · USStony Brook University · US

Funding

Vascular stabilization as a broad theraprutic platform for biodefenseU54AI065357 · NIAID · COLORADO STATE UNIVERSITY-FORT COLLINS · PI BELISLE, JOHN T · 2005 to 2013
$77.5M
Development and Formulation of Broad Spectrum Antimicrobials for BiodefenseU01AI082164 · NIAID · COLORADO STATE UNIVERSITY · PI SLAYDEN, RICHARD A · 2009 to 2010
$2.0M
NIAID NIH HHS U01 AI082164NIAID NIH HHS U54 AI065357
6 · The paper itself

Abstract

Previously, structure-based drug design was used to develop substituted diphenyl ethers with potency against the Mycobacterium tuberculosis (Mtb) enoyl-ACP reductase (InhA), however, the highly lipophilic centroid compound, SB-PT004, lacked sufficient efficacy in the acute murine Mtb infection model. A next generation series of compounds were designed with improved specificity, potency against InhA, and reduced cytotoxicity in vitro, but these compounds also had limited solubility. Accordingly, solubility and pharmacokinetics studies were performed to develop formulations for this class and other experimental drug candidates with high logP values often encountered in drug discovery. Lead diphenyl ethers were formulated in co-solvent and Self-Dispersing Lipid Formulations (SDLFs) and evaluated in a rapid murine Mtb infection model that assesses dissemination to and bacterial burden in the spleen. In vitro synergy studies were performed with the lead diphenyl ether compounds, SB-PT070 and SB-PT091, and rifampin (RIF), which demonstrated an additive effect, and that guided the in vivo studies. Combinatorial therapy in vivo studies with these compounds delivered in our Self-Micro Emulsifying Drug Delivery System (SMEDDS) resulted in an additional 1.4 log

Indexed as

AnimalsAntitubercular AgentsBacterial ProteinsDisease Models, AnimalDrug CompoundingDrug Delivery SystemsDrug DiscoveryDrug SynergismDrug Therapy, CombinationEmulsifying AgentsMice, Inbred C57BLMicrobial Sensitivity TestsMycobacterium tuberculosisOxidoreductasesPhenyl EthersSolubilityAntitubercular AgentsBacterial ProteinsEmulsifying AgentsInhA protein, MycobacteriumOxidoreductasesPhenyl EthersCombinatorial treatmentDiphenyl ethersDrug discoveryFormulationRifampinTuberculosis

Identifiers

PMID27865404
PMCPMC5117134
OpenAlexW2497082128

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.