(1) Background: The research group has developed a new small molecule, 6-Isopropyldithio-2'-deoxyguanosine analogs-YLS004, which has been shown to be the most sensitive in acute T-lymphoblastic leukemia cells. Moreover, it was found that the structure of Nelarabine, a drug used to treat acute T-lymphoblastic leukemia, is highly similar to that of YLS004. Consequently, the structure of YLS004 was altered to produce a new small molecule inhibitor for this study, named YLS010.
View Article and Find Full Text PDFIn Korea and China, ilaprazole is a widely used proton pump inhibitor in the treatment of gastric ulcers. In this study, a specific and sensitive LC-MS/MS method has been developed and validated for the quantification of ilaprazole enantiomers in the rat plasma, using -lansoprazole as the internal standard. The enantioseparation was achieved on a CHIRALPAK AS-RH column (4.
View Article and Find Full Text PDFJ Pharm Biomed Anal
November 2020
Nucleic acid is a collective term of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), and it is an essential substance in all known life forms. As numerous of studies have shown that nucleic acids can be used as therapeutic agents and the abnormality of various nucleic acid and its modification level has been proven to be closely bound up with changes in diseases such as cancer, the development of analytical methods for the nucleic acid and its modification has become one of the research hotspots in the field of life sciences. Compared with classical nucleic acid detection methods such as Northern blotting, Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) and Polymerase Chain Reaction (PCR), novel analytical methods based on nanomaterials, nucleic acid amplification strategies and biosensors can better satisfy the needs for sensitivity and simplicity in current clinical diagnosis.
View Article and Find Full Text PDFFlumatinib, indicated for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, is a structural analog of imatinib and has shown higher potency than imatinib as a BCR-ABL inhibitor. In this paper, the metabolic profile of flumatinib was studied. It was found that CYP3A4 and CYP2C8 were the main cytochrome P450 enzyme substyles catalyzing the metabolism of flumatinib, and CYP3A4 has a stronger metabolic ability for flumatinib than CYP2C8.
View Article and Find Full Text PDFColorectal cancer (CRC) is known to be the third most common cancer disease and the fourth-leading cause of cancer-related deaths worldwide. Bile acid, especially deoxycholic acid and lithocholic acid, were revealed to play an important role during carcinogenesis of CRC. In this study, we found organic solute transporter (OST), an important subunit of a bile acid export transporter OST-OST, was noticeably downregulated in CRC.
View Article and Find Full Text PDFRenal cell carcinoma (RCC) is one of the most common malignant tumors affecting the urogenital system, accounting for 90% of renal malignancies. Traditional chemotherapy options are often the front-line choice of regimen in the treatment of patients with RCC, but responses may be modest or limited due to resistance of the tumor to anticarcinogen. Downregulated expression of organic cation transporter OCT2 is a possible mechanism underlying oxaliplatin resistance in RCC treatment.
View Article and Find Full Text PDFDrug Metab Pharmacokinet
June 2019
Mandelic acid (MA) is generally used as a biomarker of the exposure of styrene, which is classified as a class of hazardous environmental pollutants, and also used as an important chiral intermediate in pharmaceutical industry. The previous studies have found the excretion of phenylglyoxylic acid (PGA) in human and rat, a metabolite of MA, was mainly from S-MA rather than R-MA. The metabolic mechanism, however, is not clear.
View Article and Find Full Text PDFBackground And Purpose: The concentrative nucleoside transporter 2 (CNT2) mediates the uptake of both natural nucleosides and nucleoside-derived drugs. Therefore, it is important both physiologically and pharmacologically. However, CNT2 expression is significantly repressed in colorectal cancer (CRC).
View Article and Find Full Text PDFThe constitutive androstane receptor (CAR) is a key sensor in xenobiotic detoxification and endobiotic metabolism. Increasing evidence suggests that CAR also plays a role in energy metabolism by suppressing the hepatic gluconeogenesis and lipogenesis. In this study, we investigated the effects of two evodia alkaloids, rutaecarpine (Rut) and evodiamine (Evo), on gluconeogenesis and lipogenesis through their activation of the human CAR (hCAR).
View Article and Find Full Text PDFMinipigs represent a good animal model because of the physiologic and anatomic similarities they share with humans. Three cytochrome P450 (CYP) 3A isozymes, CYP3A22, CYP3A29, and CYP3A46, have recently been reported to be expressed in Bama minipigs, which have limited data relating to their metabolic characteristics. In the present study, Bama minipig CYP3A22, CYP3A29, and CYP3A46 were recombinantly expressed and their metabolic manners were compared with those of human CYP3A4 and CYP3A5 and also human and Bama minipig liver microsomes.
View Article and Find Full Text PDFMini Rev Med Chem
November 2012
The plant-endophytic strains of the fungus Pestalotiopsis (Amphisphaeriaceae) are distributed throughout the world. Previous chemical investigation of members of the genus resulted in the discovery of various bioactive secondary metabolites including chromones, cytosporones, polyketides, terpenoids and coumarins with diverse structural features. The present report reviews the papers, which have appeared in the literature till now, concerning the isolation, structural elucidation, and biological activities of the secondary metabolites from Pestalotiopsis species.
View Article and Find Full Text PDF