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  • ||||||||||  prexasertib (ACR-368) / Acrivon Therap
    Journal, PARP Biomarker, PD(L)-1 Biomarker, IO biomarker:  MYC amplification sensitizes TNBC to CHK1 inhibitors. (Pubmed Central) -  Apr 13, 2025   
    Our subsequent results revealed that the novel second-generation CHK1 inhibitor, prexasertib, exhibited a more pronounced inhibitory effect in MYC-overexpressed TNBC cells compared to other DNA damage repair inhibitors, including ATR, WEE1, and PARP inhibitors...In conclusion, our findings demonstrated that MYC overexpression characterizes an aggressive TNBC subtype, enabling synergistic lethality with CHK1 inhibitors. CHK1 inhibitors will be a potential therapeutic strategy in TNBC patients with MYC overexpression.
  • ||||||||||  Review, Journal:  Newly developed antibiotics against multidrug-resistant and carbapenem-resistant Gram-negative bacteria: action and resistance mechanisms. (Pubmed Central) -  Apr 2, 2025   
    Porin modifications reduce the influx of antibiotics, whereas overexpression of efflux pumps, particularly those in the resistance-nodulation-cell division (RND) family, actively expels antibiotics from bacterial cells, significantly lowering intracellular drug concentrations and leading to treatment failure.This review examines the mechanisms of action, resistance profiles, and pharmacokinetic/pharmacodynamic characteristics of newly developed antibiotics designed to combat infections caused by MDR and carbapenem-resistant Gram-negative pathogens. The antibiotics discussed include ceftazidime-avibactam, imipenem-relebactam, ceftolozane-tazobactam, meropenem-vaborbactam, aztreonam-avibactam, delafloxacin, temocillin, plazomicin, cefiderocol, and eravacycline.
  • ||||||||||  prexasertib (ACR-368) / Acrivon Therap
    Journal:  Antitumor Activity of Radiation Therapy Combined with Checkpoint Kinase Inhibition in SHH/p53-Mutated Human Medulloblastoma. (Pubmed Central) -  Mar 27, 2025   
    Here, we investigated the potential radiosensitizing effects of the checkpoint kinase inhibitors (Chk-is) prexasertib (Chk1/2) and SAR-020106 (Chk1) in human SHH/p53-mutated MB in vitro and in vivo...However, high-dose Chk-is may compromise the RT effect, possibly through anti-proliferative activity. Furthermore, we demonstrate, for the first time, the intracranial antitumor activity of the Chk1-specific inhibitor SAR-020106.
  • ||||||||||  tetracycline / Generic mfg.
    Journal:  C10-Benzoate Esters of Anhydrotetracycline Inhibit Tetracycline Destructases and Recover Tetracycline Antibacterial Activity. (Pubmed Central) -  Mar 14, 2025   
    The best inhibitors recovered tetracycline antibiotic activity at concentrations as low as 2 ?M, producing synergistic scores <0.5 in the fractional inhibitory concentration index (FICI) against TDase-expressing strains of E. coli and clinical P. aeruginosa. The C10-benzoate ester derivatives of aTC reported here are promising new leads for the development of tetracycline drug combination therapies to overcome TDase-mediated antibiotic resistance.
  • ||||||||||  Journal:  New Kids on the Block: Estimating Use of Next-generation Gram-negative Antibiotics Across Greater Than 700 Hospitals in the United States. (Pubmed Central) -  Mar 5, 2025   
    In recent years, new broad-spectrum antibiotics targeting Gram-negative organisms have been introduced, including cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, eravacycline, imipenem-relebactam, omadacycline, and meropenem-vaborbactam...In contrast, piperacillin-tazobactam was prescribed in 731 719 (18.8%) and colistin in 570 (0.01%) admissions...Ceftazidime-avibactam and ceftolozane-tazobactam remain the most frequently prescribed new antibiotics, with uptake of subsequently approved agents trailing. New antibiotics are most commonly used as treatment for sepsis among patients with multiple comorbidities.
  • ||||||||||  Journal:  Comparative phenotypic and genotypic antimicrobial susceptibility surveillance in Achromobacter spp. through whole genome sequencing. (Pubmed Central) -  Feb 27, 2025   
    In general, the species other than A. xylosoxidans showed lower MIC50 and MIC90, especially to carbapenems and ?-lactamase inhibitor combinations like piperacillin-tazobactam, meropenem-vaborbactam, and imipenem-relebactam...Our study provides phenotypic data regarding identification and susceptibility testing and correlates this with the genotypic characterization of 109 clinical isolates belonging to Achromobacter spp. This comprehensive study sheds light on the phenotypic and genotypic character of this bacteria, that is of increasing clinical relevance in hospital-acquired infections.
  • ||||||||||  prexasertib (ACR-368) / Acrivon Therap
    Trial completion, Trial completion date, Trial primary completion date:  A Study of the Drugs Prexasertib, Irinotecan, and Temozolomide in People With Desmoplastic Small Round Cell Tumor and Rhabdomyosarcoma (clinicaltrials.gov) -  Feb 20, 2025   
    P1/2,  N=21, Completed, 
    This comprehensive study sheds light on the phenotypic and genotypic character of this bacteria, that is of increasing clinical relevance in hospital-acquired infections. Active, not recruiting --> Completed | Trial completion date: Sep 2025 --> Feb 2025 | Trial primary completion date: Sep 2025 --> Feb 2025
  • ||||||||||  Journal, Adverse events:  Pharmacovigilance analysis of drug-induced hypofibrinogenemia using the FDA Adverse Event Reporting System. (Pubmed Central) -  Jan 31, 2025   
    This analysis of FAERS data identified 52 drugs associated with hypofibrinogenemia, most (88.5%) of which do not mention this risk in their prescribing information. These findings demonstrate the need for the monitoring of blood fibrinogen and may serve as a reference for the explore of the characteristics and underlying mechanism of drug-induced hypofibrinogenemia in the real world.
  • ||||||||||  Cubicin (daptomycin) / Merck (MSD), Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
    Preclinical, Journal:  Multicentre evaluation of in vitro activity of contezolid against drug-resistant Staphylococcus and Enterococcus. (Pubmed Central) -  Dec 12, 2024   
    High-risk clones like K. pneumoniae ST307 and A. baumannii ST2 underscore the necessity of prudent antibiotic use. Contezolid demonstrated significant in vitro antibacterial activity against methicillin-resistant Staphylococcus, VRE and linezolid-resistant E. faecalis.
  • ||||||||||  decitabine / Generic mfg.
    Decitabine Synergizes with Replication Checkpoint Inhibitors in TP53-Mutated Acute Myeloid Leukemia () -  Dec 7, 2024 - Abstract #ASH2024ASH_7862;    
    https://clinicaltrials.gov/, ChiCTR2300078646. Prior reports suggest that DNA methyltransferase inhibitors (DNMTi), such as decitabine and azacitidine, form covalent DNA-DNMT1 adducts and invoke a DNA damage response (DDR) characterized by activation of the ATR-CHK1 pathway, including in TP53MT AML samples...Similar results were obtained from decitabine (EC50 = 300
  • ||||||||||  Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
    Clinical, Preclinical, Journal:  In vitro activities of eravacycline against clinical bacterial isolates: a multicenter study in Guangdong, China. (Pubmed Central) -  Dec 3, 2024   
    Eravacycline (ERV), a novel tetracycline derivative, exhibits broad-spectrum antibacterial activity, but data on the bacterial activity against Chinese bacterial isolates are very scarce...Since there were no intermediate breakpoints for the eravacycline, the MIC values measured by the ETEST method might result in lower CA and higher VME and ME. This study provides MIC values of eravacycline against Gram-positive and Gram-negative pathogens in four hospitals in Guangdong Province, and eravacycline is an effective therapeutic candidate for common bacteria.
  • ||||||||||  Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
    Journal:  Eradication of Pseudomonas aeruginosa Persister Cells by Eravacycline. (Pubmed Central) -  Nov 16, 2024   
    The effects of eravacycline on persister control were further validated in vivo using a lung infection model in mice. Collectively, these results demonstrate the possibility to control persister cells of bacterial pathogens by targeting dormancy.
  • ||||||||||  Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
    Journal, PD(L)-1 Biomarker, IO biomarker:  Eravacycline improves the efficacy of anti-PD1 immunotherapy via AP1/CCL5 mediated M1 macrophage polarization in melanoma. (Pubmed Central) -  Nov 13, 2024   
    As expected, application of ERV improved the efficacy of anti-PD1. Overall, our results approved that ERV enhances the efficacy of anti-PD1 immunotherapy in melanoma by promoting the polarization of M1 macrophages, which provided novel therapeutic strategy for improving the effectiveness of melanoma anti-PD1 immunotherapy.