- |||||||||| Mycobutin (rifabutin) / Pfizer, Lupin, Rifalazil (benzoxazinorifamycin) / TrioBiotics Pharma
Journal: CRISPR Interference-Based Inhibition of MAB_0055c Expression Alters Drug Sensitivity in Mycobacterium abscessus. (Pubmed Central) - Jun 19, 2023
Our results showed that silencing the MAB_0055c gene lead to increased rifamycin susceptibility depending on the hydroquinone moiety...The study found that silencing the gene lead to increased rifabutin and rifalazil susceptibility...These findings underscore the potential of using CRISPRi as a tool for elucidating resistance mechanisms, essential drug targets, and drug mechanisms of action, which could pave the way for more effective treatments for M. abscessus infections. The results of this study could have important implications for the development of new therapeutic options for this challenging-to-treat bacterial infection.
- |||||||||| Rifalazil (benzoxazinorifamycin) / TrioBiotics
Preclinical, Journal: Therapeutic efficacy of rifalazil (KRM-1648) in a M. ulcerans-induced Buruli ulcer mouse model. (Pubmed Central) - Oct 13, 2022
At the final point of the experiment, all the treated mice (5mg/kg/day; n = 6, 10mg/kg/day; n = 7) survived and had no signs of M. ulcerans infection. These results indicate that the rifamycin analogue, RLZ, is efficacious in the treatment of an advanced M. ulcerans infection mouse model.
- |||||||||| Mycobutin (rifabutin) / Pfizer, Lupin, Rifalazil (benzoxazinorifamycin) / TrioBiotics
Journal: Optimization of Benzoxazinorifamycins to Minimize hPXR Activation for the Treatment of Tuberculosis and HIV Coinfection. (Pubmed Central) - Aug 17, 2022
We have utilized a structure-based drug design approach to synthesize and test 15 benzoxazinorifamycins (bxRIFs), congeners of the clinical candidate rifalazil, to minimize human pregnane X receptor (hPXR) activation while improving potency against MTB...Importantly, we have analogues that are essentially equipotent against replicating MTB and non-replicating persister MTB, a property that is correlated with faster kill rates and may lead to shorter treatment durations. This work provides a proof of principle that the ansamycin core remains an attractive and effective scaffold for novel and dramatically improved RIFs.
- |||||||||| Rifalazil (benzoxazinorifamycin) / TrioBiotics
Journal: Optimization of Benzoxazinorifamycins to Improve Mycobacterium tuberculosis RNA Polymerase Inhibition and Treatment of Tuberculosis. (Pubmed Central) - Aug 17, 2022
Rifampin (RMP), a very potent inhibitor of the Mycobacterium tuberculosis (MTB) RNA polymerase (RNAP), remains a keystone in the treatment of tuberculosis since its introduction in 1965...We have utilized a structure-based drug design approach to synthesize and test novel benzoxazinorifamycins (bxRIF), congeners of the clinical candidate rifalazil...These results suggest that 27a may exhibit a faster kill rate than RMP, which could possibly reduce the clinical treatment time. Our synthetic protocol enabled the synthesis of ∼2 g of 27a at >95% purity in 3 months, demonstrating the feasibility of scale-up synthesis of bxRIFs for preclinical and clinical studies.
- |||||||||| doxycycline / Generic Mfg.
Retrospective data, Review, Journal: Non-standard treatment for uncomplicated Chlamydia trachomatis urogenital infections: a systematic review. (Pubmed Central) - Oct 29, 2019
We expect that newly emerging rifamycins shall appear as potential tools for TB treatment in the near future. The paucity of existing data highlights the need for further adequately powered studies to evaluate rifalazil, delayed release doxycycline, levofloxacin and other agents for the treatment of uncomplicated CT infections.
|
