Delving into the Latest Updates on Solithromycin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Solithromycin (JAN/USAN)

+ [3]

Target

50S subunit

Mechanism

50S subunit inhibitors(50S ribosomal subunit inhibitors), Protein biosynthesis inhibitors

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication

Respiratory Tract Infections

Inactive Indication

airway diseaseCommunity Acquired PneumoniaCommunity-acquired bacterial pneumonia+ [3]

Originator Organization

Cubist Pharmaceuticals LLC

Active Organization

FUJIFILM Pharmaceuticals USA, Inc.

Inactive Organization

Melinta Therapeutics, Inc.Cempra Pharmaceuticals, Inc.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC43H65FN6O10

InChIKeyIXXFZUPTQVDPPK-ZAWHAJPISA-N

CAS Registry760981-83-7

AbstractEnzymatic platforms for producing malonyl‐CoA‐based extender units required for polyketide biosynthesis are often based on malonyl‐CoA ligases such as MatB from Rhizobium trifolii and Rhodopseudomonas palustris. However, despite broad interest in the fluorination of polyketides and prior success with engineering MatB homologs, the suitability of MatB for accessing the tertiary substituted fluoromethylmalonyl‐CoA needed to produce flurithromycin and solithromycin has not yet been reported. Herein, we report the structure‐guided engineering of a MatB homolog to optimize the production of fluoromethylmalonyl‐CoA, resulting in a variant with increased conversion and providing a platform to produce a suitable building block mixture for fluorinated macrolide production. Additionally, the mutant demonstrated broad utility for various substituted malonyl‐CoAs. The MatB mutant sets the stage to access fluorinated macrolides by coupling it with altered PKS machinery to install fluorinated malonyl‐CoA into macrolide scaffolds.

31 Jul 2024·Journal of Clinical and Translational Hepatology

Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease/Metabolic Dysfunction-associated Steatotic Liver Disease

Review

Author: Liu, Yu-Dong ; Hu, Ye ; Sun, Chao ; Chen, Ying ; Fan, Jian-Gao

Given the global prevalence and rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD), the absence of licensed medications is striking. A deeper understanding of the heterogeneous nature of MASLD has recently contributed to the discovery of novel groups of agents and the potential repurposing of currently available medications. MASLD therapies center on four major pathways. Considering the close relationship between MASLD and type 2 diabetes, the first approach involves antidiabetic medications, including incretins, thiazolidinedione insulin sensitizers, and sodium-glucose cotransporter 2 inhibitors. The second approach targets hepatic lipid accumulation and the resultant metabolic stress. Agents in this group include peroxisome proliferator-activated receptor agonists (e.g., pioglitazone, elafibranor, saroglitazar), bile acid-farnesoid X receptor axis regulators (obeticholic acid), de novo lipogenesis inhibitors (aramchol, NDI-010976), and fibroblast growth factor 21/19 analogs. The third approach focuses on targeting oxidative stress, inflammation, and fibrosis. Agents in this group include antioxidants (vitamin E), tumor necrosis factor α pathway regulators (emricasan, pentoxifylline, ZSP1601), and immune modulators (cenicriviroc, belapectin). The final group targets the gut (IMM-124e, solithromycin). Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side effects. This review aimed to provide an update on these medications.

01 Jun 2024·Indian Journal of Microbiology

Solithromycin in Combination with Other Antimicrobial Agents Against the Carbapenem Resistant Klebsiella pneumoniae (CRKP)

Article

Author: Sharma, Shingini ; Samuel Raj, V. ; Sharma, Amit ; Rani, Kusum ; Tripathi, Shyam ; Sheba, Poornima

Klebsiella pneumoniae is considered as the most common pathogen of hospital-acquired pneumonia. K. pneumoniae has emerged as the superbug which had shown multidrug resistance (MDR) as well as extensively drug resistance. Carbapenem resistant K. pneumoniae (CRKP) has become a menace for the treatment with monotherapy of the patients mainly admitted in intensive care units. Hence, in the present study we collected total 187 sputum isolates of K. pneumoniae and performed the antimicrobial susceptibility testing by using the automated Vitek-2 system and broth micro-dilution method (67 CRKP). The combination study of solithromycin with meropenem, colistin, cefotaxime, piperacillin and tazobactam, nitrofurantoin, tetracycline, levofloxacin, curcumin and nalidixic acid was performed by using checkerboard assay. We observed the high rate of resistance towards ampicillin, cefotaxime, ceftriaxone, cefuroxime and aztreonam. The colistin and tigecycline were the most sensitive drugs. The CRKP were 36%, maximum were from the patients of ICUs. The best synergistic effect of solithromycin was with meropenem and cefotaxime (100%), colistin and tetracycline (80%). So, these combinations can be a choice of treatment for the infections caused by MDR CRKP and other Gram-negative bacteria where the monotherapy could not work.

1

News (Medical) associated with Solithromycin

30 Mar 2023

·www.drugs.com

Not Enough Antibiotics in Drug Development Pipeline, WHO Says

THURSDAY, March 30, 2023 -- Only 12 new antibiotics entered the market between 2017 and 2021, and too few currently are under development against critical pathogens, according to a World Health Organization presentation at the 33rd European Congress of Clinical Microbiology & Infectious Diseases, held from April 15 to 18 in Copenhagen, Denmark. Valeria Gigante, Ph.D., from the WHO Antimicrobial Resistance Division in Geneva, and colleagues updated the state of the antibiotic landscape. They reported that of the 12 antibiotics approved, only cefiderocol is able to target all the pathogens deemed critical by WHO. Of the 27 antibiotics currently under development, only solithromycin, which is used to treat community-acquired pneumonia and other infections, is awaiting market authorization and seven are in phase 3 trials. Only four of the 27 have new mechanisms of action, and most are not new drug classes. Only six of the 27 are considered innovative enough to overcome antibiotic resistance using WHO criteria, and only two of the six target highly drug-resistant forms of these microbes. "There is a major gap regarding products addressing multidrug resistant pathogens, such as Acinetobacter baumannii and Pseudomonas aeruginosa ," Gigante said in a statement. "Few new innovative antibiotics are expected in the coming years. We have no silver bullets." More Information Posted March 2023

Phase 3Qualified Infectious Disease Product

100 Deals associated with Solithromycin

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External Link

KEGG	Wiki	ATC	Drug Bank
D09965	Solithromycin	J01FA16	DB09308

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Community-acquired bacterial pneumonia	Phase 1	CZ	Melinta Therapeutics, Inc.	01 Dec 2012
Community-acquired bacterial pneumonia	Phase 1	PL	Melinta Therapeutics, Inc.	01 Dec 2012
Community-acquired bacterial pneumonia	Phase 1	EC	Melinta Therapeutics, Inc.	01 Dec 2012
Community-acquired bacterial pneumonia	Phase 1	RU	Melinta Therapeutics, Inc.	01 Dec 2012
Community Acquired Pneumonia	Phase 1	EU	Cempra Pharmaceuticals, Inc.	-
Community-acquired bacterial pneumonia	Discovery	PL	Melinta Therapeutics, Inc.	01 Dec 2012
Community-acquired bacterial pneumonia	Discovery	RU	Melinta Therapeutics, Inc.	01 Dec 2012
Community-acquired bacterial pneumonia	Discovery	EC	Melinta Therapeutics, Inc.	01 Dec 2012
Community-acquired bacterial pneumonia	Discovery	CZ	Melinta Therapeutics, Inc.	01 Dec 2012
Community Acquired Pneumonia	Discovery	EU	Cempra Pharmaceuticals, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02210325 (Pubmed \| Lancet Infect Dis) Manual	Phase 3	Gonorrhea First line	261	solithromycin	(qkojncxvds) = ugnrsfzybj qmkpurnyot (ybcoykyizb ) View more	Negative	01 Aug 2019
				ceftriaxone+azithromycin	(qkojncxvds) = zgogrpzrlc qmkpurnyot (ybcoykyizb ) View more
NCT02605122 (CTgov)	Phase 2/3	Community-acquired bacterial pneumonia	97	Solithromycin (Solithromycin)	fjszfoyfbf(srkbmvrgil) = jtvugnimab vusdwgqcpe (tpztnaecfr, twbezycqoj - rmansjmfzh) View more	-	03 Jan 2019
				Standard of Care (Standard of Care)	fjszfoyfbf(srkbmvrgil) = dxzycqudsx vusdwgqcpe (tpztnaecfr, ywxnailwvt - fkzxkfplqr) View more
NCT01968733 (SOLITAIRE-IV, Pubmed \| Clin Infect Dis) Manual	Phase 3	Community-acquired bacterial pneumonia	863	Solithromycin	(paaqgxnxbv) = bgmaezrrpe gjwviefcqh (eszizevifw ) View more	Non-inferior	15 Oct 2016
				Moxifloxacin	(paaqgxnxbv) = djdkfacguh gjwviefcqh (eszizevifw ) View more
NCT01756339 (SOLITAIRE-ORAL, Pubmed \| Lancet Infect Dis) Manual	Phase 3	Community-acquired bacterial pneumonia	860	Placebo+solithromycin	(hcvdvttsno) = obszqsaxzf opdvdidaxj (gukecdnrzs ) View more	Non-inferior	01 Apr 2016
				moxifloxacin	(hcvdvttsno) = rltgwglxvg opdvdidaxj (gukecdnrzs ) View more
NCT01966055 (Pubmed \| Antimicrob Agents Chemother)	Phase 1	-	13	Solithromycin	(jmlwzkbexo) = tajgxzaoqq mhghjsstud (spndgnitzg, 0.61)	-	01 Apr 2016
NCT01591447 (Pubmed \| Clin Infect Dis)	Phase 2	Gonorrhea	59	Solithromycin 1200 mg	klvxtaunpb(bvsftfuvnu) = ercanoiivu yvzwjlxqnp (mloixgfuqv ) View more	Positive	01 Oct 2015
ERS2015	Phase 3	Pulmonary Disease, Chronic Obstructive \| Asthma \| Community Acquired Pneumonia	860	Oral solithromycin	badyosjmob(kuwnclqvtx) = 36.6% vs 35.6% of patients experienced adverse events with Oral solithromycin vs Oral moxifloxacin telygdpwlj (mljsyttphp ) View more	-	01 Sep 2015
				Oral moxifloxacin
NCT01168713 (Pubmed \| Antimicrob Agents Chemother)	Phase 2	Community-acquired bacterial pneumonia	132	Solithromycin 800 mg	dmzobwehyl(rclnvqdjlo) = lmzdodzusj fuolywmlos (smdifuyjmt ) View more	-	01 Jun 2013
				Levofloxacin 750 mg	dmzobwehyl(rclnvqdjlo) = jycayxtzhc fuolywmlos (smdifuyjmt ) View more