- |||||||||| Fetroja (cefiderocol) / Shionogi, Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva, Zavicefta (ceftazidime/avibactam) / Pfizer, AbbVie
Preclinical, Journal: Evaluation of the in vitro susceptibility of clinical isolates of NDM-producing Klebsiella pneumoniae to new antibiotics included in a treatment regimen for infections. (Pubmed Central) - Apr 22, 2024
Using the "strip stacking" method, determining cumulative sensitivity to ceftazidime/avibactam and aztreonam demonstrated 100% in vitro sensitivity to this combination among the tested strains...Due to the safety of using both drugs, cost effectiveness, and the broadest indications for use among the tested antibiotics, this therapy should be the first-line treatment for carbapenemase-producing Enterobacterales infections. Nevertheless, a comprehensive evaluation of the efficacy of treating infections caused by NDM-producing K. pneumoniae strains should include not only in vitro susceptibility assessment but also an analysis of clinical cases.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Journal: Detection and characterization of eravacycline heteroresistance in clinical bacterial isolates. (Pubmed Central) - Apr 11, 2024
Furthermore, fitness cost measurements revealed a growth trade-off in CRKP upon acquiring drug resistance, highlighting fitness costs as crucial factors in the emergence of ERV HR in CRKP. Overall, the findings of the current study suggest that ERV HR in clinical strains presents a potential obstacle in its clinical application.
- |||||||||| bevantolol (SOM3355) / SOM Biotech
Enrollment closed: Efficacy and Safety on SOM3355 in Huntington's Disease Chorea (clinicaltrials.gov) - Apr 11, 2024
P2, N=129, Active, not recruiting,
Overall, the findings of the current study suggest that ERV HR in clinical strains presents a potential obstacle in its clinical application. Recruiting --> Active, not recruiting
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
A CASE OF ERAVACYCLINE INDUCED STEATOHEPATITIS (Hall A) - Mar 14, 2024 - Abstract #DDW2024DDW_5898;
Eravacycline (ERV), a novel tetracycline antibiotic, used in the treatment of complicated intrabdominal infections, may cause liver toxicity, particularly in the form of hepatic steatosis...The culture grew vancomycin-resistant enterococcus, aspergillus, and mycobacterium avium complex...Considering the profound liver damage that may occur with this adverse reaction, care should be taken in administering ERV to patients who have concomitant liver disease. It is recommended that providers should be instructed as to the possible signs and symptoms of toxicity and be monitored for evidence of idiosyncratic reaction or liver failure.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap
Targeting CTPS1 and nucleotide biosynthesis pathways as a novel therapeutic approach in MYC-amplified medulloblastoma (Section 43) - Mar 5, 2024 - Abstract #AACR2024AACR_6536;
Previously, the CHK1 inhibitor, prexasertib, demonstrated robust brain accumulation and targeting of G3 MB in pre-clinical models...We further demonstrated robust synergy of CHK1 inhibition with either glutamine antagonists or other inhibitors of the de novo pyrimidine synthesis pathway, prolonging in vivo survival in an orthotopic xenograft G3 MB model. The results of this investigation confirm CTPS1 as a novel target in G3 MB, pinpoint a dependency on de novo pyrimidine rather than purine biosynthesis, and identifies a novel rational combination for treatment in MYC-amplified MB patients.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap
Combination of a chk1/2 dual inhibitor (prexasertib) and gemcitabine reveals a novel intrinsic synergy mechanism in head and neck squamous cell carcinoma (Section 29) - Mar 5, 2024 - Abstract #AACR2024AACR_5416;
Cell cycle analysis revealed a replication catastrophe and increased pH2AX across multiple HNSCC cell lines following combination treatment.Our findings highlight the significance of CHK1/2 inhibition coupled with nucleoside analog-induced DNA damage in unveiling novel intrinsic signaling mechanisms in HNSCC. These insights offer a promising avenue for targeted therapeutic strategies to enhance treatment efficacy and outcomes in HNSCC.This work has been supported by the MGC, FC, P&MC, and BBSR at the H. Lee Moffitt Cancer Center & Research Institute, a comprehensive cancer center designated by the National Cancer Institute (P30-CA076292).
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Chk1/2 inhibition enhances response to lurbinectedin treatment in small cell lung cancer (Section 23) - Mar 5, 2024 - Abstract #AACR2024AACR_5325;
Western blot analysis of intracellular proteins from the same SCLC cell lines treated with both drugs demonstrate dose-dependent effects on cell death marker cPARP, DNA damage marker ?H2AX, and DDR/cell cycle pathway kinases cdk1 and 2. Ongoing experiments seek to replicate results using alternative Chk1/2 inhibitors, and to explore the effect of lurbinectedin-Chk1/2 inhibitor combination treatment on antitumor immune effector function by in vitro co-culture.
- |||||||||| nitazoxanide / Generic mfg.
Journal: Transcriptional Differential Analysis of Nitazoxanide-Mediated Anticanine Parvovirus Effect in F81 Cells. (Pubmed Central) - Feb 28, 2024
Moreover, when the cell cycle was regulated with cell cycle checkpoint kinase 1 (Chk1) inhibitor MK-8776 or Prexasertib HCl, both inhibitors inhibited the CPV. In summary, the transcriptome differential analysis results presented in this paper lay the foundation for further research on the molecular mechanism and potential targets of NTZ anti-CPV.
- |||||||||| tetracycline / Generic mfg.
IS38 - cIAI challanges and new tetracycline-based therapies (Hall M) - Feb 27, 2024 - Abstract #ECCMID2024ECCMID_1826;
The microbiologist's perspective will delve into resistance patterns and their implications for therapy. Additionally, the session will feature real-life patient cases illustrating the use of eravacycline in a country where it has already been launched.
- |||||||||| Preclinical, Journal: In Vitro Antimicrobial Activity of Five Newly Approved Antibiotics against Carbapenemase-Producing Enterobacteria-A Pilot Study in Bulgaria. (Pubmed Central) - Jan 22, 2024
To solve the problem with pan-drug resistant and extensively drug-resistant Gram-negative microbes, newly approved drugs such as ceftazidime/avibactam, cefiderocol, plazomicin, meropenem/vaborbactam, and eravacycline have been introduced in practice...The isolates were highly resistant to standard-group antibiotics, except they were susceptible to tigecycline (83.1%), colistin (79.7%), fosfomycin (32.8%), and aminoglycosides (20.3-35.9%)...This study is the first report to show patterns of susceptibility to five newly approved antibiotics among molecularly characterized isolates in Bulgaria. The data may contribute to both the improvement of treatment of individual patients and the choice of infection control strategy and antibiotic policy.
- |||||||||| Review, Journal: New Antibiotics for the Treatment of Nosocomial Central Nervous System Infections. (Pubmed Central) - Jan 22, 2024
The halogenated tetracycline eravacycline does not reach CSF concentrations sufficient to treat colistin-resistant Gram-negative bacteria with usual intravenous dosing...An additional IVT can overcome the limited penetration of many new antibiotics into CSF. It should be considered for patients in which the CNS infection responds poorly to systemic antimicrobial therapy alone.
- |||||||||| Review, Journal: Novel drug candidates against antibiotic-resistant microorganisms: A review. (Pubmed Central) - Jan 18, 2024
In addition to these identified drug candidates, continued in vitro and in vivo studies are required to investigate small molecules with potential antibacterial effects screened by computational receptor docking. As drug discovery progresses, preclinical and clinical studies should also be extensively conducted on the currently available therapeutic agents to unravel their potential antibacterial effect and spectrum of activity, as well as safety and efficacy profiles.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Journal, HEOR: Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022. (Pubmed Central) - Jan 15, 2024
This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.
- |||||||||| Review, Journal: Reviewing novel treatment options for carbapenem-resistant enterobacterales. (Pubmed Central) - Jan 6, 2024
Development of antibiotics with activity against metallo-?-lactamase producing Enterobacterales is eagerly awaited and there are promising new compounds in clinical trials. Finally, more clinical research is needed to optimize and individualize treatment approaches, which will help guide antimicrobial stewardship initiatives aimed at reducing the spread of CRE and development of further resistance.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap
Targeting CTPS1 and nucleotide biosynthesis pathways as a novel therapeutic approach in MYC-amplified medulloblastoma (Room 109-110) - Nov 11, 2023 - Abstract #SNO2023SNO_1391;
Interestingly, the DDR inhibitor prexasertib (CHKi) robustly targets MYC-amplified MB tumors in pre-clinical models...We further demonstrated robust synergy of CHKi with other clinically relevant de novo pyrimidine metabolism inhibitors. The results of this investigation confirm CTPS1 and the de novo pyrimidine metabolism pathway as targets in MYC-amplified MB and identifies a novel rational combination for treatment in patients.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap
Radiotherapy with concurrent inhibition of Chek2 activates STING in gliomas (Exhibit Hall A/B) - Nov 11, 2023 - Abstract #SNO2023SNO_494;
Interestingly, when the in vitro-grown GBM6 cells were pretreated with Chek1/2 inhibitor prexasertib for 48 hours prior to the 2 Gy radiotherapy exposure, there was 10 fold reduction in the activation of Chek2 as compared to the radiotherapy alone group...Our in vitro findings suggest an inverse relationship between the activation of Chek2 and STING. In conclusion, radiotherapy with concurrent inhibition of Chek2 offers a novel therapeutic combination to modulate STING activation in gliomas.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Preclinical, Journal: Synergistic effects of eravacycline combined with fluconazole Against resistant Candida albicans in vitro and in vivo. (Pubmed Central) - Nov 9, 2023
The results of RNA-sequencing and qPCR showed that the mechanism of synergistic inhibition on resistant C. albicans was related to the inhibition of DNA replication and cell meiosis. These results indicate that the combination of ERV and FLC effectively inhibits resistant C. albicans both in vitro and in vivo and lay the foundation for a potential novel treatment option for candidiasis.
- |||||||||| Sivextro (tedizolid) / Merck (MSD), Nabriva Therap, Fetroja (cefiderocol) / Shionogi, Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
FDA event, Journal: Computational insights into VacA toxin inhibition: harnessing FDA-approved antibiotics against Helicobacter pylori. (Pubmed Central) - Nov 8, 2023
Furthermore, we also identified the hotspot residue like Asn-506, Tyr-529, and Phe-483 which control the interaction. Concisely, we identified antibiotics that can be repurposed against VacA of H. pylori and explored their molecular mechanism of interaction with VacA.Communicated by Ramaswamy H. Sarma.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Review, Journal: Prolonged course of eravacycline leading to acute pancreatitis. (Pubmed Central) - Nov 6, 2023
Clinicians should be aware of this potential adverse effect of eravacycline and should not initiate eravacycline in those with risk factors for acute pancreatic injury. However, acute pancreatitis should be suspected in all patients complaining of symptoms followed by immediate discontinuation of eravacycline.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap
Mitotic Dysregulation Sensitizes Malignant Stem Cells to CHK1 Inhibition in SF3B1-Mutant Myeloid Neoplasms (Marriott Marquis - Pacific Ballroom) - Nov 3, 2023 - Abstract #ASH2023ASH_1362;
In conclusion, we developed a precise gene editing strategy of human HSCs to identify prexasertib as a promising therapy for SF3B1m myeloid neoplasms, and implicate the mitotic function of CHK1 as a SF3B1m sensitivity. The safety and toxicity profiles displayed in early phase clinical trials make prexasertib a suitable agent for further clinical investigation in SF3B1m MDS and its advanced stages.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Journal: Investigation of the Efficacy of Cinnamaldehyde, Cannabidiol and Eravacycline in a Malaria Model (Pubmed Central) - Oct 31, 2023
In this study, it was aimed to investigate the antimalarial activity of cinnamaldehyde (CIN) and cannabidiol (CBD) which have shown various biological activities such as potent antimicrobial activity and eravacycline (ERA), a new generation tetracycline derivative, in an in vivo malaria model...In this study, five groups were formed: the CIN group, the CBD group, the ERA group, the chloroquine group (CQ) and the untreated group (TAG)...It has been determined that all three active subtances tested in this study suppressed the development of Plasmodium parasites in an in vivo mouse model and prolonged the life span of the mice. It is thought that the strong antimalarial activity of CIN and CBD shown in the study and the possible positive effect of ERA on the clinical course can be improved by combining them with the existing and potential antimalarial molecules.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap
P2 data, Journal, BRCA Biomarker, PARP Biomarker: A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer. (Pubmed Central) - Oct 22, 2023
P2
Prexasertib demonstrated durable single agent activity in a subset of patients with recurrent ovarian cancer regardless of clinical characteristics, BRCA status, or prior therapies, including PARPi. There was no obvious correlation with genomic alterations in responders vs non-responders, emphasizing the need for alternative biomarker approaches for responder identification.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap, navitoclax (ABT 263) / AbbVie
Preclinical, Journal: Simultaneous inhibition of Chk1 and Bcl-xL induces apoptosis in (Pubmed Central) - Oct 22, 2023
Treatment to control volume ratios were calculated as 63.2% for prexasertib, 79.4% for navitoclax, and 36.8% for prexasertib and navitoclax. These findings suggest that the simultaneous inhibition of Chk1 and Bcl-xL may be an effective treatment for pancreatic cancer.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Journal: Use of Eravacycline for Acinetobacter baumannii Infections: A Case Series. (Pubmed Central) - Sep 16, 2023
Pharmacogenomics analysis showed three therapeutic agents (NVP-BEZ235, LY2606368, and rutin) This case series describes the clinical course of 10 patients who received eravacycline antimicrobial therapy for a variety of different Acinetobacter baumannii infection types at a community care hospital.
|
