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First-in-human phase 1 study of the arginase inhibitor INCB001158 alone or combined with pembrolizumab in patients with advanced or metastatic solid tumours.
BMJ Oncol
May 2024
Sarah Cannon Cancer Institute, Nashville, Tennessee, USA.
Objective: The arginase inhibitor INCB001158 was evaluated for safety (primary endpoint) in locally advanced or metastatic solid tumours; pharmacokinetics, pharmacodynamics and efficacy were also assessed.
Methods And Analysis: In this non-randomised, open-label, three-part phase 1 study, INCB001158 was orally administered two times per day as monotherapy or in combination with intravenous pembrolizumab 200 mg every 3 weeks. Dose expansion was conducted in tumour-type cohorts (with or without prior anti-PD-1/PD-L1 (programmed death protein 1/programmed death ligand 1) therapy).
Discovery of Pyrrolopyrazine Carboxamide Derivatives as Potent and Selective FGFR2/3 Inhibitors that Overcome Mutant Resistance.
J Med Chem
January 2025
Insilico Medicine Shanghai Ltd, Suite 901, Tower C, Changtai Plaza, 2889 Jinke Road, Pudong New District, Shanghai 201203, China.
Fibroblast growth factor receptors (FGFRs) are established oncogenic drivers in various solid tumors. However, the approved FGFR inhibitors face challenges with acquired resistance and dose-limiting adverse effects associated with FGFR1/4 inhibition, limiting therapeutic efficacy. Herein, we systematically explored linker and electrophile moieties based on the pyrrolopyrazine carboxamide core and identified aniline α-fluoroacrylamide as an effective covalent warhead.
View Article and Find Full Text PDFWithania somnifera-derived phytochemicals as Bcl-B inhibitors in cancer therapy: A computational approach from byte to bench to bedside.
Biochem Biophys Res Commun
January 2025
Department of Biotechnology, Sharda School of Engineering and Technology, Sharda University, Greater Noida, India. Electronic address:
Cancer is the second foremost cause of fatalities associated with non-communicable diseases across the globe, affecting multiple organs and often necessitating costly treatments with adverse side effects. Apoptosis, the body's natural cell death process, plays a crucial role in the prevention of cancer, but it's often disrupted in cancer cells, allowing uncontrolled proliferation. Restoring apoptosis in cancer cells is one of the promising therapeutic strategies to curb tumor growth and enhance clinical outcomes.
View Article and Find Full Text PDFEfficacy and safety of dutasteride in the treatment of alopecia: a comprehensive review.
Expert Opin Pharmacother
January 2025
Mediprobe Research Inc, London, ON, Canada.
Introduction: Alopecia affects many individuals, with androgenetic alopecia (AGA) being the most common form in both men and women. The exact etiology of AGA is unclear. The systemic treatments of AGA include 5-alpha reductase inhibitors (finasteride, dutasteride), low-dose oral minoxidil.
View Article and Find Full Text PDFPersistent low concentrations of antiepileptics in a critically ill paediatric patient: an example of multiple potential drug interactions.
BMJ Case Rep
January 2025
Clinical Pharmacology, Aalborg University Hospital, Aalborg, Region Nordjylland, Denmark
A middle childhood boy with epilepsy exhibited persistent low concentrations of valproic acid, lamotrigine and topiramate for over 1 month, primarily due to pharmacokinetic interactions involving fosphenytoin, meropenem and phenobarbital. Awareness of these clinically significant interactions is crucial for ensuring effective seizure control. However, further research is needed to establish optimal evidence-based treatment strategies in complex paediatric cases.
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