- |||||||||| Solithera (solithromycin) / Melinta Therap, Fujifilm Holdings
Journal: Synthesis and structure-activity relationships of novel 14-membered 2-fluoro ketolides with structural modification at the C11 position. (Pubmed Central) - Feb 26, 2024
A series of novel C11 substituted 14-membered 2-fluoro ketolides were synthesized and evaluated for their antibacterial activity against erythromycin-resistant and erythromycin-susceptible clinical isolates and strains from ATCC...Molecular docking suggested compound 12d oriented the macrolide ring and side chain similarly to solithromycin (SOL)...Therefore this research would offer a new perspective for further structural optimization of the C11 side chain. Based on the results of antibacterial activity, cytotoxicity and structural diversity, 5 compounds (11a, 11b, 11h, 12d and 12i) were selected for the stability testing of human liver microsomes and compound 11a exhibited preferable metabolic stability.
- |||||||||| Solithera (solithromycin) / Melinta Therap, Fujifilm Holdings
Journal: Efficacy, safety, and tissue penetration of solithromycin in Japanese patients with otorhinolaryngological infections. (Pubmed Central) - Dec 9, 2023
Based on the results of antibacterial activity, cytotoxicity and structural diversity, 5 compounds (11a, 11b, 11h, 12d and 12i) were selected for the stability testing of human liver microsomes and compound 11a exhibited preferable metabolic stability. Based on the findings, it is suggested that solithromycin is useful for the treatment of otorhinolaryngological infections.
- |||||||||| solithromycin (CEM-101) / Melinta Therap, Fujifilm Holdings
Clinical, Journal: Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia. (Pubmed Central) - Jun 15, 2022
However, much more information is required to clarify the molecular mechanisms underlying the inhibition of CLCA1 and ANO1 by solithromycin. Intravenous and oral solithromycin were generally well-tolerated and associated with clinical improvement in the majority of participants treated for CABP.
- |||||||||| Journal: Discovery and Development of Antibacterial Agents: Fortuitous and Designed. (Pubmed Central) - May 26, 2022
This article aims to review the investigational and recently approved antibacterials with a focus on their structure, mechanisms of action/resistance, and spectrum of activity. Delving deep, their success or otherwise in various phases of clinical trials is also discussed while attributing the same to various causal factors.
- |||||||||| solithromycin (CEM-101) / Melinta Therap, Fujifilm Holdings, Sovaldi (sofosbuvir) / Gilead
Journal: Biocatalytic Asymmetric Construction of Secondary and Tertiary Fluorides from β-Fluoro-α-ketoacids. (Pubmed Central) - May 12, 2022
The reactivity of HpcH towards these fluoro-donors grants access to enantiopure secondary or tertiary fluorides. In addition to representing the first synthesis of tertiary fluorides via biocatalytic carboligation, the afforded products could improve the diversity of fluorinated building blocks and enable the synthesis of fluorinated drug analogs.
- |||||||||| solithromycin (CEM-101) / Melinta Therap, Fujifilm Holdings
Journal: Synthesis, biological evaluation, and computational analysis of biaryl side-chain analogs of solithromycin. (Pubmed Central) - Feb 26, 2022
The biological activity of each analog was evaluated in terms of ribosomal affinity ( K d determined by fluorescence polarization), as well as minimum inhibitory concentration assays (MICs). Density functional theory (DFT) studies of a simple binding site model identify key H-bonding interactions that modulate the potency of solithromycin analogs.
- |||||||||| solithromycin (CEM-101) / Melinta Therap, Fujifilm Holdings
Fatty acid synthases (FASs) enable access to new-to-nature compounds (Sapphire I/J (Hilton San Diego Bayfront)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_7044;
(ii) The mammalian FASs features high transacylation rates for a wide range of substrates. We inserted the mammalian FAS transferase domain (MAT) into modular PKSs to enable the in vitro semisynthesis of new polyketides, including fluorinated polyketides with a macrolide scaffold similar to the next-generation antibiotic solithromycin (2-Fluoro-YC-17, see Figure).Semisynthetic approach to first produce the fluoro-methyl disubstituted macrolactone, which is then biotransformed to the fluorinated derivative of the antibiotic YC-17 using strain DHS316.
- |||||||||| rifampicin / Generic mfg.
Journal: Azaindole Based Potentiator of Antibiotics against Gram-Negative Bacteria. (Pubmed Central) - Nov 18, 2021
Our studies indicate that this selective potentiation is probably through destabilization of the outer membrane's integrity, known to be regulated by the lipopolysaccharides (LPS). Thus, the azaindole based compounds described here open opportunities for those antibiotics that are otherwise ineffective due to LPS mediated entry barriers in Gram-negative bacteria.
- |||||||||| solithromycin (CEM-101) / Melinta Therap, Fujifilm Holdings
Journal: Solithromycin Can Specifically Induce Macrolide-Lincosamide-Streptogramin B Resistance. (Pubmed Central) - Jul 4, 2021
The results described here can serve as a good basis to guide further activities directed toward the discovery of more potent macrolide anti-infectives. Solithromycin does not induce erm(A) and erm(C) gene expression, but does induce erm(B) gene expression, although to a weaker extent than that seen for macrolides.
- |||||||||| solithromycin (CEM-101) / Melinta Therap, Fujifilm Holdings, gepotidacin (GSK2140944) / GSK, zoliflodacin (ETX0914) / Entasis Therap, Global Antibiotic Research and Development Partnership
Review, Journal: Neisseria gonorrhoeae Antimicrobial Resistance: Past to Present to Future. (Pubmed Central) - May 15, 2021
Thus, this review focuses on the mechanisms of resistance to recommended antimicrobials in the past and present time. The approaches by the scientific community in the development of novel technologies such as whole-genome sequencing to predict antimicrobial resistance, track gonococcal transmission, as well as, introduce new therapeutics like Solithromycin, Zoliflodacin, and Gepotidacin were also discussed.
- |||||||||| nafithromycin (WCK 4873) / Wockhardt
Preclinical, Journal: Assessment of the in vitro cytochrome P450 (CYP) inhibition potential of Nafithromycin, a next generation lactone ketolide antibiotic. (Pubmed Central) - Mar 4, 2021
Nafithromycin exhibits potent activity against MDR Streptococcus pneumoniae including erythromycin and telithromycin-resistant resistant strains...To facilitate comparative assessment of drug-drug interaction potential, CYP inhibitory activities of nafithromycin was evaluated in comparison with clarithromycin, telithromycin, cethromycin and solithromycin...k/K ratio of nafithromycin was 3 to 153 fold lower than comparator drugs, further substantiating its lower affinity for CYP3A4/5. In sum, weaker inhibition and lower k/K ratio for CYP3A4/5, points towards nafithromycin's lower propensities towards clinical drug-drug interactions as compared to other macrolides/ketolides antibiotics.
- |||||||||| solithromycin (CEM-101) / Melinta Therap, Fujifilm Holdings
Journal: Recent Advances in the Development of Macrolide Antibiotics as Antimicrobial Agents. (Pubmed Central) - Dec 30, 2020
In this paper, total synthetic methods for MA that include erythromycin A (ERY), azithromycin (AZM), the clinical candidate solithromycin (CEM-101), as well as 14-membered and 15-membered azaketolides have been systematically reviewed on the basis of the literatures reported previously. The total synthetic methods we describe here helps to accelerate the discovery of newer MA to deal with the serious problem of bacterial resistance.
- |||||||||| Review, Journal: Investigational and Experimental Drugs for Community-Acquired Pneumonia: the Current Evidence. (Pubmed Central) - Nov 28, 2020
Delafloxacin, omadacycline and lefamulin are the most recently approved antibiotics for CAP...New antimicrobials, such as solithromycin and nemonoxacin, are currently being studied in Phase III clinical trials...These include zabofloxacin, aravofloxacin, nafithromycin, TP-271, gepotidacin, radezolid, delpazolid, and CAL02. The preliminary results of these clinical trials allow us to assure that most of these drugs may play a role in the future treatment of CAP.
- |||||||||| solithromycin (CEM-101) / Melinta Therap, Fujifilm Holdings
PK/PD data, Journal: Differentiating the Pharmacodynamics and Toxicology of Macrolide and Ketolide Antibiotics. (Pubmed Central) - Nov 19, 2020
This mini-perspective describes that structurally similar macrolides/ketolides have clearly mechanistically distinct effects. Understanding these effects could help in developing and securing regulatory approval of a new macrolide/ketolide that is active against macrolide-resistant pathogenic bacteria.
- |||||||||| ceftriaxone / Generic mfg.
Journal: New treatment options for Neisseria gonorrhoeae in the era of emerging antimicrobial resistance. (Pubmed Central) - Sep 25, 2020
At present, zoliflodacin and gepotidacin appear to be the most promising antimicrobial agents in clinical development...Given this observation, it is unlikely that either of these new agents could be promoted for monotherapy of gonorrhoea. The pre-clinical pipeline remains relatively empty of agents likely to progress to clinical development for gonorrhoea treatment and increased investment into gonorrhoea-specific drug discovery is recommended.
- |||||||||| solithromycin (CEM-101) / Melinta Therap, Fujifilm Holdings
Journal: Synthesis and biological evaluation of solithromycin analogs against multidrug resistant pathogens. (Pubmed Central) - Sep 13, 2020
We have synthesized analogs of solithromycin using Cu(I)-mediated click chemistry. Evaluation of the analogs using Minimum Inhibitory Concentration (MIC) assays against resistant Staphylococcus aureus, Escherichia coli, and multidrug resistant pathogens Enterococcus faecium and Acinetobacter baumannii showed they possess potencies similar to those of solithromycin, thus demonstrating their potential as future therapeutics to combat the existential threat of multidrug resistant pathogens.
- |||||||||| solithromycin (CEM-101) / Melinta Therap, Fujifilm Holdings
Clinical, Journal: A Dried Blood Spot Analysis for Solithromycin in Adolescents, Children, and Infants: A Short Communication. (Pubmed Central) - Aug 27, 2020
P1
Evaluation of the analogs using Minimum Inhibitory Concentration (MIC) assays against resistant Staphylococcus aureus, Escherichia coli, and multidrug resistant pathogens Enterococcus faecium and Acinetobacter baumannii showed they possess potencies similar to those of solithromycin, thus demonstrating their potential as future therapeutics to combat the existential threat of multidrug resistant pathogens. Solithromycin concentrations in DBS were similar to those measured in LPS and did not require correction for hematocrit or protein binding.
- |||||||||| Journal: Emerging antibiotics for Community-Acquired Pneumonia. (Pubmed Central) - May 26, 2020
Among the known antibiotic classes, solithromycin (a macrolide), nemonoxacin (a quinolone), and delafloxacin and zabofloxacin (both fluoroquinolones), have been studied in phase II and III in clinical trials. The availability of these new antibiotics may offer opportunities to improve the empirical treatment for community-acquired pneumonia.
- |||||||||| Journal: New antibiotics for community-acquired pneumonia. (Pubmed Central) - May 15, 2020
CAP continues to be an important infection because of its impact on patient outcomes especially in the elderly and immunocompromised hosts. The availability of new antibiotics offers an opportunity for enhanced empiric treatment of the antibiotic-resistant bacterial pathogens associated with CAP.
- |||||||||| solithromycin (CEM-101) / Melinta Therap, Fujifilm Holdings
Clinical, Journal: Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting. (Pubmed Central) - Feb 29, 2020
The way forward will require renewed political will, new funding initiatives and collaborations across academic and commercial research and public health programs.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
- |||||||||| Review, Journal: Current and future pharmacological therapies for NAFLD/NASH. (Pubmed Central) - Oct 9, 2019
Among a variety of medications in development, four agents such as OCA, elafibranor, ASK1 inhibitor, and CVC are currently being evaluated in an international phase 3 trial for the treatment of NASH. Within the next few years, the availability of therapeutic options for NASH will hopefully curb the rising trend of NASH-related diseases.
- |||||||||| solithromycin (CEM-101) / Cempra, Fujifilm Holdings
Journal: Potency of solithromycin against fast and slow growing chlamydial organisms. (Pubmed Central) - Sep 26, 2019
Sol may therefore represent a potential new clinical treatment for Chlamydia infections. Selective perturbation of the T3S system suggests a novel mode of antibacterial action for Sol that warrants further investigation.
- |||||||||| solithromycin (CEM-101) / Cempra, Fujifilm Holdings
Journal: Metabolism, Excretion and Mass Balance of Solithromycin in Humans. (Pubmed Central) - Jul 17, 2019
Overall oxidative pathways, presumably carried out mostly by CYP3A4, represented the majority of the metabolism with-acetylation present to a lesser extent. No disproportionate human metabolites were observed.
- |||||||||| Clinical, Review, Journal: The role of new antibiotics in the treatment of acute adult community acquired pneumonia (Pubmed Central) - May 29, 2019
Results are still pending regarding the efficacy and any possible advantages of these new molecules, and also the emergence of drug resistant bacteria. Although these drugs share some advantages, they should not be selected over antibiotics usually prescribed for the treatment of CAP.
- |||||||||| Avelox (moxifloxacin) / Bayer
Journal: Solithromycin: A novel ketolide antibiotic. (Pubmed Central) - May 26, 2019
Solithromycin is a novel ketolide antibiotic with activity against a broad spectrum of intracellular organisms, including those displaying macrolide resistance. While demonstrating noninferiority to a current first-line agent in the treatment of CABP, concerns for drug-induced liver injury and infusion-site reactions have placed its regulatory future in doubt.
- |||||||||| meropenem / generics, ceftazidime / generics
Journal: New antibiotics in infection treatment (Pubmed Central) - Mar 28, 2019
The new MRX-1 preapplate, alongside tedizolid and cadazolid, are further oxazolidinones that show significant activity against multi-resistant Gram-positive pathogens. The presented palette of new molecules with antimicrobial activity will certainly significantly improve the effectiveness of antibiotic therapy.
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