Last update 19 Sep 2024

PFOR

Last update 19 Sep 2024

Basic Info

Synonyms

丙酮酸合酶, CpPNO, Pyruvate dehydrogenase [NADP(+)]

+ [1]

Introduction

May have an important role in respiratory metabolism. Cryptosporidium have a relic mitochondrion with no function in energy metabolism so it is not known if PFOR has a function.

Drugs associated with PFOR

Nitazoxanide

Target

PFOR

Mechanism

PFOR inhibitors

Active Org.

Romark, L.C. [+2]

Originator Org.

Romark, L.C.

Active Indication

Cryptosporidiosis [+7]

Inactive Indication

Acquired Immunodeficiency Syndrome [+14]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date22 Nov 2002

Nitrofurazone

Target

PFOR

Mechanism

PFOR inhibitors

Active Org.

Hunan Xiangyikang Pharmaceutical Co. Ltd. [+1]

Originator Org.

Shire LLC

Active Indication

Hemorrhage [+3]

Inactive Indication

Superficial bacterial infection of skin

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date04 Oct 1945

Nitrofurazone/Ephedrine Hydrochloride

Target

PFOR x adrenergic receptor

Mechanism

PFOR inhibitors [+1]

Active Org.-

Originator Org.-

Active Indication

Nasal Obstruction

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

115

Clinical Trials associated with PFOR

NCT05157269 / Not yet recruitingPhase 3

Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild COVID-19 in Subjects Not at High Risk of Severe Illness

The purpose of this study is to determine whether nitazoxanide (NTZ) is safe and effective for treatment of mild COVID-19 illness. Adults and adolescent participants will be followed for approximately 28 days.

Start Date01 Aug 2024

Sponsor / Collaborator

Romark, L.C.

NCT05157243 / Not yet recruitingPhase 3

Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Efficacy and Safety of Nitazoxanide for Treatment of Mild or Moderate COVID-19 in Subjects at High Risk of Severe Illness

The purpose of this study is to determine whether nitazoxanide (NTZ) is safe and effective in treating mild or moderate COVID-19 illness in adults and adolescents at highest risk for severe outcomes. Each participant will be followed for approximately 28 days.

Start Date01 Aug 2024

Sponsor / Collaborator

Romark, L.C.

NCT06010992 / RecruitingPhase 2IIT

A Clinical Study Evaluating the Potential Benefit of Nitazoxanide in Patients With Type 2 Diabetes Mellitus

Diabetes mellitus (DM) is a complex metabolic disorder characterized by hyperglycemia and abnormalities in carbohydrate, fat, and protein metabolism. Despite the advancement in anti-diabetic drug therapy, most patients fail to achieve optimal glycemic control. This highlights the need for more effective strategies to control type 2 diabetes mellitus.
Nitazoxanide (NTZ), a broad-spectrum anti-infective drug with activity against various protozoa, helminthes, bacteria, and viruses, was identified as peroxisome proliferative activated receptor gamma (PPARγ) agonist using one dimensional drug profile matching. Additionally, it improved insulin sensitivity in insulin-resistant type 2 diabetic rats. Therefore, this study is designed to evaluate the efficacy of nitazoxanide as adjunctive therapy in patients with type 2 diabetes mellitus.

Start Date01 Oct 2023

Sponsor / Collaborator

Tanta University

[+1]

100 Clinical Results associated with PFOR

100 Translational Medicine associated with PFOR

0 Patents (Medical) associated with PFOR

242

Literatures (Medical) associated with PFOR

01 Aug 2024·Journal of Environmental Management

Comparison of anaerobic co-digestion of vacuum toilet blackwater and kitchen waste under mesophilic and thermophilic conditions: Reactor performance, microbial response and metabolic pathway

Article

Author: Liu, Yanping ; Wang, Ziang ; Li, Haixiang ; Zhu, Jia ; Yang, Ziyi ; Wang, Pingbo

Co-digestion of kitchen waste (KW) and black water (BW) can be considered as an attractive method to efficiently achieve the clean energy from waste. To find the optimal operation parameters for the co-digestion, the effects of different temperatures (35 and 55 °C) and BW:KW ratios on the reactor performances, microbial communities and metabolic pathways were studied. The results showed that the optimum BW:KW ratio was 1:3.6 and 1:4.5 for mesophilic and thermophilic optimal reactors, with methane production of 449.04 mL/g VS and 411.90 mL/g VS, respectively. Microbial communities showed significant differences between the reactors under different temperatures. For bacteria, increasing BW:KW ratio significantly promoted Defluviitoga enrichment (1.1%-9.5%) under thermophilic condition. For Archaea, the increase in BW:KW ratio promoted the enrichment of Methanosaeta (8.6%-56.4%) in the mesophilic reactor and Methanothermobacter (62.0%-89.2%) in the thermophilic reactor. The analysis of the key enzymes showed that, acetoclastic methanogenic pathway performed as the dominant under mesophilic condition, with high abundance of Acetate-CoA ligase (EC:6.2.1.1) and Pyruvate synthase (EC:1.2.7.1). Hydrogenotrophic methanogenic pathway was the main pathway in the thermophilic reactors, with high abundance of Formylmethanofuran dehydrogenase (EC:1.2.99.5).

05 Sep 2023·Microorganisms

Genetic Variability of the Internal Transcribed Spacer and Pyruvate:Ferredoxin Oxidoreductase Partial Gene of Trichomonas vaginalis from Female Patients.

Article

Author: Gonzalez-Arenas, Nelly Raquel ; Maravilla, Pablo ; Sanchez-Aguillon, Fabiola ; Villalobos, Guiehdani ; Lopez-Escamilla, Eduardo ; Martinez-Hernandez, Fernando ; Martinez-Ocaña, Joel ; Romero-Valdovinos, Mirza

In the present study, we evaluated the genetic variability of the internal transcribed spacer (ITS) region and the pyruvate:ferredoxin oxidoreductase (pfor) A gene of Trichomonas vaginalis from female patients and its possible implications in the host-parasite relationship. Phylogenetic and genetics of populations analyses were performed by analyzing sequences of the ITS region and partial pfor A gene of clinical samples with T. vaginalis, as previously documented. Alignments of protein sequences and prediction of three-dimensional structure were also performed. Although no correlation between the main clinical characteristics of the samples and the results of phylogeny was found, a median-joining analysis of ITS haplotypes showed two main clusters. Also, pfor A, due to its phylogenetic divergence, could be used as a marker to confirm the genus and species of trichomonads. Alignment of protein sequences and prediction of three-dimensional structure showed that PFOR A had a highly conserved structure with two synonymous mutations in the PFOR domain, substituting a V for a G or a S for a P. Our results suggest that the role of genetic variability of PFOR and ITS may not be significant in the symptomatology of this pathogen; however, their utility as genus and species markers in trichomonads is promising.

17 May 2023·Antimicrobial agents and chemotherapy

CDBN-YGXZ, a Novel Small-Molecule Drug, Shows Efficacy against Clostridioides difficile Infection and Recurrence in Mouse and Hamster Infection Models.

Article

Author: Guang, Bing ; Hu, Xiaojun ; Tian, Dong ; Gao, Xiaofang ; Peng, Jian ; Zhang, Xiaoxia ; Wang, Ting ; Zhang, Yaying ; Xu, Jiewei ; Huang, Sheng ; Wang, Xiaohui ; Yang, Tai ; Zhan, Wei ; Liu, Jin ; Dong, Renhan ; Zeng, Yisheng

Clostridioides difficile infection (CDI) causes severe diarrhea and colitis, leading to significant morbidity, mortality, and high medical costs worldwide. Oral vancomycin, a first-line treatment for CDI, is associated with a high risk of recurrence, necessitating novel therapies for primary and recurrent CDI. A novel small-molecule compound, CDBN-YGXZ, was synthesized by modifying the benzene ring of nitazoxanide with lauric acid. The mechanism of action of CDBN-YGXZ was validated using a pyruvate:ferredoxin/flavodoxin oxidoreductase (PFOR) inhibition assay. The efficacy of CDBN-YGXZ was evaluated using the MIC test and CDI infection model in mice and hamsters. Furthermore, metagenomics was used to reveal the underlying reasons for the effective reduction or prevention of CDI after CDBN-YGXZ treatment. The inhibitory activity against PFOR induced by CDBN-YGXZ. MIC tests showed that the in vitro activity of CDBN-YGXZ against C. difficile ranging from 0.1 to 1.5 μg/mL. In the mouse and hamster CDI models, CDBN-YGXZ provided protection during both treatment and relapse, while vancomycin treatment resulted in severe relapse and significant clinical scores. Compared with global effects on the indigenous gut microbiota induced by vancomycin, CDBN-YGXZ treatment had a mild influence on gut microbes, thus resulting in the disappearance or reduction of CDI recurrence. CDBN-YGXZ displayed potent activity against C. difficile in vitro and in vivo, reducing or preventing relapse in infected animals, which could merit further development as a potential drug candidate for treating CDI.

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PFOR

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