Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Petrov2018 - C-547 a 6-methyluracil derivative with long-lasting binding and rebinding on acetylcholinesterase

ABSTRACT: C-547, a candidate drug, is a potent slow-binding inhibitor of acetyl-cholinesterase, and the focus of this PK/PD model, which investigates the metabolism and clinical effect of C-547 when it is no longer detectable in the blood. Intended for treatment of myasthenia gravis, this drug and the accompanying model offers a possible treatment for further development of drugs offering neuroprotective effects.

SUBMITTER: Johannes Meyer

PROVIDER: MODEL1910240001 | BioModels | 2019-11-13

REPOSITORIES: BioModels

ACCESS DATA

Json Xml

Publications

C-547, a 6-methyluracil derivative with long-lasting binding and rebinding on acetylcholinesterase: Pharmacokinetic and pharmacodynamic studies.

Petrov Konstantin K Zueva Irina I Kovyazina Irina I Sedov Igor I Lushchekina Sofya S Kharlamova Alexandra A Lenina Oksana O Koshkin Sergei S Shtyrlin Yurii Y Nikolsky Evgeny E Masson Patrick P

Neuropharmacology 20171224

C-547, a potent slow-binding inhibitor of acetylcholinesterase (AChE) was intravenously administered to rat (0.05 mg/kg). Pharmacokinetic profiles were determined in blood and different organs: extensor digitorum longus muscle, heart, liver, lungs and kidneys as a function of time. Pharmacokinetics (PK) was studied using non-compartmental and compartmental analyses. A 3-compartment model describes PK in blood. Most of injected C-547 binds to albumin in the bloodstream. The steady-state volume of ...[more]

PMID: 29277489

Similar Datasets

Characterization of the transcriptional response to DNA in STING KO cells

Project description:Here we demonstrate that the SIDSP induces a broad and potent antiviral response that is abrogated by treatment with the DNA-PK inhibitor, Nu7441.

2019-12-11 | GSE129436 | GEO

Transplanted human organoids empower PK/PD assessment of drug candidate for the clinic

Project description:Transplanted human organoids empower PK/PD assessment of drug candidate for the clinic

| PRJNA693268 | ENA

Transplanted human organoids empower PK/PD assessment of drug candidate for the clinic

Project description:Pharmacokinetic/pharmacodynamic (PK/PD) studies are an essential component of pre-clinical drug discovery. Current best approaches for PK/PD studies, including the analysis of novel kidney disease targeting therapeutic agents, are limited to animal models with unclear translatability to the human condition. To address this challenge, we developed a novel approach for PK/PD studies using transplanted human kidney organoids. We performed PK studies with GFB-887, an investigational new drug now in Phase 2 trials. Orally dosed GFB-887 to athymic rats that had undergone organoid transplantation resulted in measurable drug exposure in human transplanted organoids. Importantly, we established the efficacy of orally dosed GFB-887 in PD studies, where quantitative analysis showed significant protection of kidney filter cells in human organoids and endogenous rat host kidneys. This widely applicable approach demonstrates, for the first time, feasibility of using transplanted human organoids in PK/PD studies, empowering organoids to revolutionize drug discovery.

2022-06-14 | GSE165104 | GEO

Solid Digestion of Demineralized Bone as a Method to Access Potentially Insoluble Proteins and Post-translational Modifications

Project description:This study investigates the application of solid-digestion protocols on the numbers of proteins and types of post-translational modifications detectable from bone after demineralization.

2017-08-02 | MSV000081399 | MassIVE

Selective DNA-PK inhibition enhances chemotherapy and ionizing radiation activity in soft-tissue sarcomas

Project description:Purpose: Patients with advanced soft-tissue sarcomas (STSs) exhibit a poor prognosis and have few therapeutic options. DNA-dependent protein kinase catalytic subunit (DNA-PK) is a multifunctional serine—threonine protein kinase that plays a crucial role in DNA double-strand damage repair via nonhomologous end joining (NHEJ). Experimental design: To investigate the therapeutic potential of DNA-PK targeting in STS, we first evaluated the prognostic value of DNA-PK expression in two large cohorts of patients with STS. We then used the potent and selective DNA-PK inhibitor AZD7648 compound to investigate the antitumor effect of the pharmacological inhibition of DNA-PK in vitro via MTT, apoptosis, cell cycle, and proliferation assays. In vivo studies were performed with patient-derived xenograft models to evaluate the effects of AZD7648 in combination with chemotherapy or ionizing radiation on tumor growth. The mechanisms of sensitivity and resistance to DNA-PK inhibition were investigated by using a genome-wide CRISPR-Cas9 positive screen. Results: DNA-PK overexpression is significantly associated with poor prognosis in patients with sarcomas. Selective pharmacological inhibition of DNA-PK strongly synergizes with radiation- and doxorubicin-based regimen in sarcoma models. By using a genome-wide CRISPR-Cas9 positive screen, we identified genes involved in sensitivity to DNA-PK inhibition. Conclusion: DNA-PK inhibition deserves clinical investigation to improve response to current therapies in patients with sarcoma

2023-09-25 | GSE243758 | GEO

Investigation of the blood levels at a reduced dose of erlotinib with the addition of ritonavir compared to the normal dose of erlotinib

Project description:Primary objectives: Effect of the highly potent CYP3A4 inhibitor ritonavir on the pharmacokinetics (PK) of erlotinib, measured as AUC0-24h, AUCmean, Cmax and Cmin Primary endpoints: The effect of the highly potent CYP3A4 inhibitor ritonavir on the pharmacokinetics (PK) of erlotinib, measured as AUC0-24h, Cmax and Cmin.

| 2538815 | ecrin-mdr-crc

Project description:Drug-Resistant Lipid-Dependent Differentially Detectable Mycobacterium tuberculosis

| PRJNA749058 | ENA

Roles of PKLR in NAFLD using loss- and gain-of-function mouse models

Project description:The etiology of non-alcoholic fatty liver disease (NAFLD) is poorly understood, with males and Mexican population exhibiting markedly increased susceptibility. Using a systems genetics approach, involving multi-omic analysis of ~100 inbred strains, we recently identified several candidate genes driving NAFLD. We investigated the role of one of these candidates, liver pyruvate kinase (L-PK or Pklr) in NAFLD using patient samples and mouse models. We examined L-PK expression in mice of both sexes and in a cohort of bariatric surgery patients. We used liver-specific loss- and gain-of-function strategies in independent animal models of diet-induced steatosis and fibrosis, involving both sexes. Following treatment, we measured several metabolic phenotypes associated with obesity, insulin resistance, dyslipidemia, liver steatosis and fibrosis. Furthermore, liver tissues were used for gene expression and western blots, and liver mitochondria for bioenergetics. Our results demonstrate that L-PK acts in a male-specific manner in the development of liver steatosis and fibrosis. Given that NAFLD/NASH exhibit sexual dimorphism, our results have important implications for the development of personalized therapeutics.

2021-01-19 | GSE151182 | GEO

Sex-specific roles of PKLR in NAFLD using gain-of-function mouse models

Project description:The etiology of non-alcoholic fatty liver disease (NAFLD) is poorly understood, with males and Mexican population exhibiting markedly increased susceptibility. Using a systems genetics approach, involving multi-omic analysis of ~100 inbred strains, we recently identified several candidate genes driving NAFLD. We investigated the role of one of these candidates, liver pyruvate kinase (L-PK or Pklr) in NAFLD using patient samples and mouse models. We examined L-PK expression in mice of both sexes and in a cohort of bariatric surgery patients. We used liver-specific loss- and gain-of-function strategies in independent animal models of diet-induced steatosis and fibrosis, involving both sexes. Following treatment, we measured several metabolic phenotypes associated with obesity, insulin resistance, dyslipidemia, liver steatosis and fibrosis. Furthermore, liver tissues were used for gene expression and Western blots, and liver mitochondria for bioenergetics. Our results demonstrate that L-PK acts in a male-specific manner in the development of liver steatosis and fibrosis. Given that NAFLD/NASH exhibit sexual dimorphism, our results have important implications for the development of personalized therapeutics.

2021-01-19 | GSE157201 | GEO

Gene expression data from lymphoblastoid cell lines from participants in the Genetics of Microangiopathic Brain Injury study

Project description:European-American individuals of the GENOA cohort participating in the “Genetics of Microangiopathic Brain Injury” substudy, which investigates the genetic basis of alteration in brain structure detectable by magnetic resonance imaging. This analysis investigated the association of gene expression with age (at the time of cell transformation).

2013-09-15 | GSE49531 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data