Evidence map›Paper›PMID 36470124›Full record

ArticleTuberculosis (Edinburgh, Scotland)2023

Microbiological profile, preclinical pharmacokinetics and efficacy of CRS0393, a novel antimycobacterial agent targeting MmpL3.

Urs A Ochsner, Mary A De Groote, Thale C Jarvis, Hang Liu, Tessa Youmans, Teresa Hoang, Wendy Ribble, Joshua Day, Wei Li, Camron Pearce and 11 more

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

Article in Tuberculosis (Edinburgh, Scotland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Nitric oxide-releasing prodrug for the treatment of complexAntimicrobial agents and chemotherapy · 2024
    Article
  5. Review
  6. New therapeutic strategies forExpert review of anti-infective therapy
    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

21 authors at 4 institutions in 1 country.

Urs A OchsnerCrestone, Inc., 6075 Longbow Dr, Boulder, CO, USA. Electronic address: uochsner@crestonepharma.com.
Mary A De GrooteCrestone, Inc., 6075 Longbow Dr, Boulder, CO, USA.
Thale C JarvisCrestone, Inc., 6075 Longbow Dr, Boulder, CO, USA.
Hang LiuCrestone, Inc., 6075 Longbow Dr, Boulder, CO, USA.
Tessa YoumansCrestone, Inc., 6075 Longbow Dr, Boulder, CO, USA.
Teresa HoangCrestone, Inc., 6075 Longbow Dr, Boulder, CO, USA.
Wendy RibbleCrestone, Inc., 6075 Longbow Dr, Boulder, CO, USA.
Joshua DayCrestone, Inc., 6075 Longbow Dr, Boulder, CO, USA.
Wei LiMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, 200 West Lake Street, Colorado State University, Fort Collins, CO, USA.
Camron PearceMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, 200 West Lake Street, Colorado State University, Fort Collins, CO, USA.
Amanda WalzMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, 200 West Lake Street, Colorado State University, Fort Collins, CO, USA.
Chandra M PanthiJohns Hopkins University, 1550 Orleans Street, Baltimore, MD, USA.
Binayak RimalJohns Hopkins University, 1550 Orleans Street, Baltimore, MD, USA.
Casey M StevensUniversity of Oklahoma, Department of Chemistry and Biochemistry, 101 Stephenson Parkway, Norman, OK, USA.
Helen I ZgurskayaUniversity of Oklahoma, Department of Chemistry and Biochemistry, 101 Stephenson Parkway, Norman, OK, USA.
Mary JacksonMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, 200 West Lake Street, Colorado State University, Fort Collins, CO, USA.
Diane OrdwayMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, 200 West Lake Street, Colorado State University, Fort Collins, CO, USA.
Mercedes Gonzalez-JuarreroMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, 200 West Lake Street, Colorado State University, Fort Collins, CO, USA.
Xicheng SunCrestone, Inc., 6075 Longbow Dr, Boulder, CO, USA.
Gyanu LamichhaneJohns Hopkins University, 1550 Orleans Street, Baltimore, MD, USA.
Clifford MasonCrestone, Inc., 6075 Longbow Dr, Boulder, CO, USA.
Crestone (United States) · USColorado State University · USJohns Hopkins University · USUniversity of Oklahoma · US

Funding

MmpL3 as a target for novel anti-TB agentsR01AI116525 · NIAID · COLORADO STATE UNIVERSITY · PI JACKSON, MARY · 2015 to 2024
$5.3M
NIAID NIH HHS R01 AI116525
6 · The paper itself

Abstract

The benzothiazole amide CRS0393 demonstrated excellent in vitro activity against nontuberculous mycobacteria (NTM), including M. abscessus isolates from cystic fibrosis (CF) patients, with minimum inhibitory concentrations (MICs) of ≤0.03-0.5 μg/mL. The essential transport protein MmpL3 was confirmed as the target via analysis of spontaneous resistant mutants and further biological profiling. In mouse pharmacokinetic studies, intratracheal instillation of a single dose of CRS0393 resulted in high concentrations of drug in epithelial lining fluid (ELF) and lung tissue, which remained above the M. abscessus MIC for at least 9 hours post-dose. This exposure resulted in a penetration ratio of 261 for ELF and 54 for lung tissue relative to plasma. CRS0393 showed good oral bioavailability, particularly when formulated in kolliphor oil, with a lung-to-plasma penetration ratio ranging from 0.5 to 4. CRS0393 demonstrated concentration-dependent reduction of intracellular M. abscessus in a THP-1 macrophage infection model. CRS0393 was well tolerated following intranasal administration (8 mg/kg) or oral dosing (25 mg/kg) once daily for 28 days in dexamethasone-treated C3HeB/FeJ mice. Efficacy against M. abscessus strain 103 was achieved via the intranasal route, while oral dosing will need further optimization. CRS0393 holds promise for development as a novel agent with broad antimycobacterial activity.

Indexed as

Cystic FibrosisMycobacterium Infections, NontuberculousMycobacterium tuberculosisAnimalsAnti-Bacterial AgentsLungMiceMicrobial Sensitivity TestsNontuberculous MycobacteriaAnti-Bacterial AgentsAntibacterialEfficacyMmpL3NTMPharmacokineticsTuberculosis

Identifiers

PMID36470124
PMCPMC9892229
OpenAlexW4310209560

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.