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The primary mechanism for highly potent inhibition of HIV-1 maturation by lenacapavir.
PLoS Pathog
January 2025
Division of Infectious Diseases, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States of America.
Lenacapavir (LEN) is a highly potent, long-acting antiretroviral medication for treating people infected with muti-drug-resistant HIV-1 phenotypes. The inhibitor targets multifaceted functions of the viral capsid protein (CA) during HIV-1 replication. Previous studies have mainly focused on elucidating LEN's mode of action during viral ingress.
View Article and Find Full Text PDFNovel isoxazole thiophene-containing compounds active against Mycobacterium tuberculosis.
Bioorg Med Chem Lett
January 2025
Calibr-Skaggs Institute for Innovative Medicines, a division of Scripps Research, La Jolla, CA 92037, United States. Electronic address:
Screening of the ChemDiv molecular library in cholesterol media against Mycobacterium tuberculosis (Mtb) H37Rv strain identified a novel isoxazole thiophene hit as a putative Rv1625c/Cya activator with a promising in vitro activity and good pharmacokinetic properties. Twenty-nine analogs were synthesized to assess the structure-activity relationships (SAR) to further improve potency. The most notable analog was P15, which showed an intramacrophage EC = 1.
View Article and Find Full Text PDFIdentifying Allosteric Small-Molecule Binding Sites of Inactive NS2B-NS3 Proteases of Pathogenic .
Viruses
December 2024
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, CA 92093-0657, USA.
Dengue, West Nile, Zika, Yellow fever, and Japanese encephalitis viruses persist as significant global health threats. The development of new therapeutic strategies based on inhibiting essential viral enzymes or viral-host protein interactions is problematic due to the fast mutation rate and rapid emergence of drug resistance. This study focuses on the NS2B-NS3 protease as a promising target for antiviral drug development.
View Article and Find Full Text PDFOutcomes of Idecabtagene Vicleucel Therapy in Patients with Relapsed/Refractory Multiple Myeloma: A Single-Institution Experience.
Biomedicines
December 2024
Department of Medicine, Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA 92093, USA.
Idecabtagene vicleucel (ide-cel), an anti-B-cell maturation chimeric antigen receptor T-cell therapy, represents an unprecedented treatment option for relapsed/refractory multiple myeloma (R/R MM). Nevertheless, given its limitations, including the risk of adverse effects and unclear durability of efficacy, there remains a need to report the real-world clinical outcomes of ide-cel therapy in patients with R/R MM, as well as explore host predictive factors for therapy. We performed a single-center retrospective analysis of 25 adult patients with R/R MM who received ide-cel between 2021 and 2023 at the University of California San Diego Health.
View Article and Find Full Text PDFThe Role of Sex and Gender in Acute Kidney Injury - Consensus Statements from the 33 Acute Disease Quality Initiative.
Kidney Int
January 2025
Department of Critical Care, King's College London, Guy's & St Thomas' Hospital, London, UK.
Sex differences exist in acute kidney injury (AKI), and the role that sex and gender play along the AKI care continuum remains unclear. The 33 Acute Disease Quality Initiative meeting evaluated available data on the role of sex and gender in AKI and identified knowledge gaps. Data from experimental models, pathophysiology, epidemiology, clinical care, gender, social determinants of health, education, and advocacy were reviewed.
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