Benthic diatoms of the genus Cocconeis contain a specific apoptogenic activity. It triggers a fast destruction of the androgenic gland in the early post-larval life of the marine shrimp Hippolyte inermis, leading to the generation of small females. Previous in vitro investigations demonstrated that crude extracts of these diatoms specifically activate a dose-dependent apoptotic process in human cancer cells (BT20 breast carcinoma) but not in human normal lymphocytes. Here, a bioassay-guided fractionation has been performed to detect the apoptogenic compound(s). Various HPLC separation systems were needed to isolate the active fractions, since the apoptogenic metabolite is highly active, present in low amounts and is masked by abundant but non-active cellular compounds. The activity is due to at least two compounds characterized by different polarities, a hydrophilic and a lipophilic fraction. We purified the lipophilic fraction, which led to the characterization of an active sub-fraction containing a highly lipophilic compound, whose molecular structure has not yet been identified, but is under investigation. The results point to the possible medical uses of the active compound. Once the molecular structure has been identified, the study and modulation of apoptotic processes in various types of cells will be possible.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917286 | PMC |
http://dx.doi.org/10.3390/md12010547 | DOI Listing |
Sci Total Environ
January 2025
Department of Natural Resource Sciences, McGill University, Sainte-Anne-de-Bellevue, QC H9X 3V9, Canada. Electronic address:
Mercury (Hg) and persistent organic pollutant (POP) accumulation among species and biomagnification through food webs is typically assessed using stable isotopes of nitrogen (δN) and carbon (δC) in bulk (whole) tissues. Yet, bulk isotopic approaches have limitations, notably from the potential overlap of isotope values from different dietary sources and from spatial variation in source (baseline) signals. Here, we explore the potential of fatty acid carbon isotopes (FA δC) to (1) evaluate the trophic structure of a marine food web, (2) distinguish feeding patterns among four marine mammal consumers, (3) trace contaminant biomagnification through a food web, and (4) explain interspecific variation in contaminants among high-trophic position predators.
View Article and Find Full Text PDFJ Pharm Biomed Anal
January 2025
Ryvu Therapeutics, Sternbacha 2, Cracow 30-394, Poland.
Accurate determination of plasma protein binding (PPB) is crucial in understanding the pharmacokinetics and pharmacodynamics of drugs, particularly for highly bound compounds where traditional methods may fall short. In this study, we present a pioneering approach for the precise determination of PPB that takes advantage of the lipophilicity of highly bound compounds. Twenty four highly bound compounds (with a fraction unbound (f) from 10 to 10) were tested with the most commonly used method, i.
View Article and Find Full Text PDFPhys Eng Sci Med
January 2025
Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, 14155-1339, Iran.
Gastrin-releasing peptide receptors (GRPRs) overexpressed in many cancers are known as promising biomarkers to target tumors such as prostate, breast, and lung cancers. As the early diagnosis of the cancers can serve for better treatment of the patients, [In]In-DOTA-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 ([In]In-RM2) was prepared using an in-house developed Sn/In generator. 0.
View Article and Find Full Text PDFEur J Drug Metab Pharmacokinet
December 2024
Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Objective: The objective of this study was to determine the apparent intrinsic clearance (Cl) and fraction unbound in human liver microsomes (f) of 86 marketed central nervous system (CNS) drugs and to predict the in vivo hepatic blood clearance (CL).
Methods: Cl in human liver microsomes (HLM) was determined by substrate depletion, and f was determined by equilibrium dialysis. The relationship between lipophilicity (logP) and unbound intrinsic clearance (Cl) was explored using the Biopharmaceutical Drug Disposition Classification System (BDDCS) and Extended Clearance Classification System (ECCS).
J Med Chem
December 2024
Oncology Medicinal Chemistry Worldwide Research and Development, Pfizer, Inc., 10770 Science Center Drive, La Jolla, California 92121, United States.
Hematopoietic progenitor kinase 1 (HPK1/MAP4K1) represents a high interest target for the treatment of cancer through an immune-mediated mechanism. Herein we present highlights of the drug discovery campaign within the lactam/azalactam series of inhibitors that yielded a small molecule (, PF-07265028), which was advanced to a phase 1 clinical trial (NCT05233436). Key components of the discovery effort included optimization of potency through mitigation of ligand strain as guided by the use of cocrystal structures, mitigation of ADME liabilities (plasma instability and fraction metabolism by CYP2D6), and optimization of kinase selectivity, particularly over immune-modulating kinases with high homology to HPK1.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!