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  • ||||||||||  Enhancing antitumor immunity by targeting cancer associated fibroblasts with radiation and ATM inhibition () -  May 3, 2025 - Abstract #ESTRO2025ESTRO_3012;    
    Beyond the well-established radiosensitizing effects of ATM inhibition, our findings reveal a potential novel role for ATM inhibitors in reprogramming NSCLC-CAFs into an immune-activating phenotype. This dual mechanism represents a promising approach to enhance radiotherapy-immunotherapy synergies by reducing the immunosuppressive influences of the tumor microenvironment.
  • ||||||||||  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.
  • ||||||||||  prexasertib (ACR-368) / Acrivon Therap, dordaviprone (ONC201) / Chimerix, Zepzelca (lurbinectedin) / PharmaMar, Jazz
    A novel triple combination therapy in small cell lung cancer targeting DNA damage repair as a mechanism of resistance (Section 15; Poster Board No: 21) -  Mar 25, 2025 - Abstract #AACR2025AACR_6846;    
    Prexasertib is a dual inhibitor of Chk1 and 2, protein kinases in the DDR pathway that regulate downstream cell cycle checkpoint (CCC) proteins particularly implicated in G1/S transition and G2 entry. Synergy scores and western blot data from experiments in four cell lines (H1048, H1882, H1105, H1417) point to the role of the DDR-CCC pathway in SCLC treatment resistance and offer a novel treatment modality for testing in vivo, with the ultimate view to progress into the clinic.
  • ||||||||||  Undisclosed PKMYT1 inhibitor / Roche, prexasertib (ACR-368) / Acrivon Therap, camonsertib (RP-3500) / Repare Therap
    Discovery of selective and orally bioavailable PKMYT1 inhibitor: characterization of anti-tumor activities as single and dual agents (Section 17; Poster Board No: 4) -  Mar 25, 2025 - Abstract #AACR2025AACR_3073;    
    Additionally, we observed synergistic effects when combining PKMYT1 inhibitors with standard-of-care chemotherapies that induce DNA damage, such as gemcitabine and hydroxyurea...In conclusion, our study underscores the therapeutic potential of selective PKMYT1 inhibitors in CCNE1-amplified cancers and provides a strong rationale for their combination with ATR inhibitors and DNA-damaging chemotherapies. These findings support the continued development and clinical evaluation of PKMYT1 inhibitors as a novel approach to cancer treatment.
  • ||||||||||  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.
  • ||||||||||  Stelara (ustekinumab) / J&J, Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva, Lamprene (clofazimine) / Novartis
    Hidden in Plain Sight: Identifying Mycobacterium Abscessus as the Covert Cause of Chronic Lung Cavitary Lesions (Area M, Hall F (North Building, Exhibition Level), Moscone Center; Poster Board # P1586) -  Feb 24, 2025 - Abstract #ATS2025ATS_6242;    
    Description: A 74-year-old male with history of ulcerative colitis, previously treated with Ustekinumab, presented with hemoptysis...Due to suspicion for MAC, the patient was started on Augmentin and doxycycline for two weeks...A peripherally inserted central catheter (PICC) was placed for three months of amikacin and eravacycline infusions, alongside azithromycin and clofazimine...Standard management includes long-term antibiotic regimens and regular assessments, although surgical resection may be required for localized infections. Our case underscores the necessity of including MABC in the differential for patients presenting with cavitary lung lesions to expedite diagnosis and treatment, avoiding the risk for worsening antibiotic resistance.
  • ||||||||||  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.