Delving into the Latest Updates on SPR-741 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Bacterial outer membrane proteins

Mechanism

Bacterial outer membrane proteins inhibitors

Therapeutic Areas

Infectious Diseases

Active Indication

Gram-Negative Bacterial Infections

Inactive Indication-

Originator Organization

Northern Antibiotics Oy

Active Organization

Northern Antibiotics Oy

Inactive Organization

Spero Therapeutics, Inc.

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC44H73N13O13

InChIKeyJBFNEVNUGGFPBQ-DDMCRLCFSA-N

CAS Registry1179330-52-9

Gene Sequence

Sequence Code 13986246

This is a Phase 1, single-center, multi-arm, open-label, randomized, three-period, crossover study to evaluate the drug-drug interaction, pharmacokinetics, safety, and tolerability of a single dose of SPR741 combined with each of 3 different partner antibiotics (ceftazidime or piperacillin/tazobactam or aztreonam) in healthy volunteers. Participants will be administered single doses of SPR741 alone, a single dose of SPR741 in combination with 1 of 3 different partner antibiotics, and the partner antibiotic alone in a randomized sequence. Twenty-seven (27) adult male and female normal healthy participants 18 to 55 years of age are planned to participate in the study. Women of childbearing potential will not be eligible to participate.

Start Date10 Nov 2017

Sponsor / Collaborator

Spero Therapeutics, Inc.

[+2]

NCT03022175 / CompletedPhase 1

A Two-part, Double-blind, Placebo-controlled, Phase I Study of the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of SPR741 in Healthy Volunteers

The purpose of this study is to assess the safety and tolerability of single and multiple intravenous doses of SPR741 when administered to healthy adult volunteers.

Start Date01 Dec 2016

Sponsor / Collaborator

Spero Therapeutics, Inc.

[+1]

100 Clinical Results associated with SPR-741

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100 Translational Medicine associated with SPR-741

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100 Patents (Medical) associated with SPR-741

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18

Literatures (Medical) associated with SPR-741

23 Jan 2023·Journal of Applied Microbiology

Triple combination of SPR741, clarithromycin, and erythromycin againstAcinetobacter baumanniiand its tolerant phenotype

Article

Author: Li, Yimin ; Liu, Yaqian ; Yang, Yifan ; Hussain, Zubair ; Wu, Yong ; Xu, Lanlan ; Li, Linhui ; Liu, Shasha ; She, Pengfei ; Li, Zehao

AbstractAimsExtensively drug-resistant (XDR) Acinetobacter baumannii poses a severe threat to public health due to its ability to form biofilms and persister cells, which contributes to critical drug resistance and refractory device-associated infections. A novel strategy to alleviate such an emergency is to identify promising compounds that restore the antimicrobial susceptibility of existing antibiotics against refractory infections.Methods and ResultsHere, we found a significant synergy among three combinations of SPR741, clarithromycin and erythromycin with a potent antimicrobial activity against XDR A. baumannii (SPR741/CLA/E at 8/10/10 μg ml–1 for XDR AB1069 and at 10/16/10 μg ml–1 for XDR AB1208, respectively). Moreover, the triple combination therapy exhibits a significant antipersister and antibiofilm effect against XDR strains. Mechanistic studies demonstrate that SPR741 may promote intracellular accumulation of macrolides by permeabilizing the outer membrane as well as disrupting membrane potential and further enhance the quorum sensing inhibition activity of the macrolides against XDR A. baumannii and its biofilms. In addition, the triple combination of SPR741 with clarithromycin and erythromycin was not easy to induce resistance in A. baumannii and had effective antimicrobial activity with low toxicity in vivo.Significance and Impact of the StudyCollectively, these results reveal the potential of SPR741 in combination with clarithromycin and erythromycin as a clinical therapy for refractory infections caused by XDR A. baumannii.

10 Feb 2022·ACS Medicinal Chemistry LettersQ3 · MEDICINE

Antibacterial Activity of Metergoline Analogues: Revisiting the Ergot Alkaloid Scaffold for Antibiotic Discovery

Q3 · MEDICINE

Article

Author: Johnson, Jarrod W. ; Bhando, Timsy ; Piquette, Zoë A. ; Magolan, Jakob ; Ritchie, Nikki E. ; MacNair, Craig ; Ellis, Michael J. ; Brown, Eric D. ; Saliba, Paul ; Carfrae, Lindsey

Metergoline is a semisynthetic ergot alkaloid identified recently as an inhibitor of the Gram-negative intracellular pathogen Salmonella Typhimurium (S. Tm). With the previously unknown antibacterial activity of metergoline, we explored structure-activity relationships (SARs) with a series of carbamate, urea, sulfonamide, amine, and amide analogues. Cinnamide and arylacrylamide derivatives show improved potency relative to metergoline against Gram-positive bacteria, and pyridine derivative 38 is also effective against methicillin-resistant Staphylococcus aureus (MRSA) in a murine skin infection model. Arylacrylamide analogues of metergoline show modest activity against wild-type (WT) Gram-negative bacteria but are more active against strains of efflux-deficient S. Tm and hyperpermeable Escherichia coli. The potencies against WT strains of E. coli, Acinetobacter baumannii, and Burkholderia cenocepacia are also improved considerably (up to >128-fold) with the outer-membrane permeabilizer SPR741, suggesting that the ergot scaffold represents a new lead for the development of new antibiotics.

01 Nov 2021·International Journal of Antimicrobial AgentsQ2 · MEDICINE

The cathelicidin-derived close-to-nature peptide D-11 sensitises Klebsiella pneumoniae to a range of antibiotics in vitro, ex vivo and in vivo

Q2 · MEDICINE

Article

Author: Rubén Cebrián ; Yushan Xia ; Oscar P Kuipers ; Weihui Wu ; Congjuan Xu

The outer membrane of Gram-negative bacteria constitutes a permeability barrier that prevents certain antibiotics reaching their target, thus conferring a high tolerance to a wide range of antibiotics. Combined therapies of antibiotics and outer membrane-perturbing drugs have been proposed as an alternative treatment to extend the use of antibiotics active against Gram-positive bacteria to Gram-negative bacteria. Among the outer membrane-active compounds, the outer membrane-permeabilising peptides play a prominent role. They form a group of small cationic and amphipathic molecules with the ability to insert specifically into bacterial membranes, inducing their permeabilisation and/or disruption. Here we assessed the combined effect of several compounds belonging to the main antibiotic families and the cathelicidin close-to-nature outer membrane peptide D-11 against four clinically relevant Gram-negative bacteria. The results showed that peptide D-11 displays strong synergistic activity with several antibiotics belonging to different families, in particular against Klebsiella pneumoniae, even better than some other outer membrane-active peptides that are currently in clinical trials, such as SPR741. Notably, we observed this activity in vitro, ex vivo in a newly designed bacteraemia model, and in vivo in a mouse abscess infection model. Overall, our results suggest that D-11 is a good candidate to repurpose the activity of traditional antibiotics against K. pneumoniae.

100 Deals associated with SPR-741

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