Published in Biochemical pharmacology
Deoxycytidine kinase (dCK) is an essential enzyme for production of nucleotides via the salvage pathway; DI-87 is a novel dCK inhibitor in preclinical development for use in anticancer therapy. The current study utilizes PET imaging to evaluate PK-PD relationships and to determine optimal dosing of the drug. NSG mice bearing CEM tumors had plasma a...
Published in Biochemical pharmacology
Antibiotic resistance is spreading faster than the development of new antibiotics into clinical practice. Currently, the design of antimicrobial peptides (AMPs), potential new antibacterial agents with rare antimicrobial resistance, is the available strategy to enhance the antimicrobial activity and lower the toxicity of AMPs. In this study, a pept...
Published in Biochemical pharmacology
Plitidepsin (PLD, Aplidin®), a cyclic depsipeptide originally isolated from the marine tunicate Aplidium albicans, has been recently approved by Australian regulatory authorities for the treatment of multiple myeloma patients. Plitidepsin binds to eEF1A2 and induces oxidative stress, Rac1 activation and JNK1 phosphorylation, triggering a rapid apop...
Published in Biochemical pharmacology
Endocrine disrupting chemicals disrupt normal physiological function of endogenous hormones, their receptors, and signaling pathways of the endocrine system. Most endocrine disrupting chemicals exhibit estrogen/androgen agonistic and antagonistic activities that impinge upon hormone receptors and related pathways. Humans are exposed to endocrine di...
Published in Biochemical pharmacology
Na+/K+-ATPase α1 was reported to directly interact with and recruit FGF2 (fibroblast growth factor 2), a vital cell signaling protein implicated in angiogenesis, to the inner plasma membrane for subsequent secretion. Cardenolides, a class of cardiac glycosides, were reported to downregulate FGF2 secretion upon binding to Na+/K+-ATPase α1 in a cell ...
Published in Biochemical pharmacology
Ageing is associated with progressive endothelial senescence and dysfunction, and cardiovascular risk. Circulating endothelial microvesicles (MVs) are pro-senescent and pro-inflammatory endothelial effectors in acute coronary syndrome. Omega 3 PUFAs intake was claimed beneficial in cardiovascular prevention. To investigate whether the intake of the...
Published in Biochemical pharmacology
Uncoupling protein 2 (UCP2) is a mitochondrial anion carrier which plays a key role in energy homeostasis. UCP2 is deregulated in several human cancers and has been suggested to regulate cancer metabolism. However, the role of UCP2 in gallbladder cancer has not been defined. Using clinical samples, we found highly expressed UCP2 in gallbladder canc...
Published in Biochemical pharmacology
Autoimmune uveitis (AU), a sight-threatening intraocular disorder, is still a challenge for ophthalmologists in clinic. Teriflunomide has been approved for multiple sclerosis (MS) in 2012 for its immunoregulatory function. However, the effect and mechanisms of teriflunomide in uveitis are still unknown. In this investigation, we used a murine model...
Published in Biochemical pharmacology
Andrographolide (Andro), a well-known labdane diterpenoid of Andrographis paniculata, has been reported to have anti-inflammatory effects in various inflammatory disease models. Despite ongoing efforts to elucidate the anti-inflammatory mechanism of Andro, its specific mechanism is not entirely clear. In this study, we confirmed the inhibitory effe...
Published in Biochemical pharmacology
Valproic acid (VPA), a widely prescribed antiepileptic drug, is known to induce hepatotoxicity. However, the mechanisms underlying this toxicity are not well understood. In this study, we performed a nontargeted metabolomic analysis of children with epilepsy treated with VPA (n = 23). Metabolic pathway analysis showed that the fatty acid pathway, c...
