23 Result(s)
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Article
Non-linear IV pharmacokinetics of the ATR inhibitor berzosertib (M6620) in mice
The Ataxia Telangiectasia and Rad3-related (ATR) protein complex is an apical initiator of DNA damage response pathways. Several ATR inhibitors (ATRi) are in clinical development including berzosertib (formerl...
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Article
Dose-dependent bioavailability, absorption-rate limited elimination, and tissue distribution of the ATR inhibitor BAY-1895344 (elimusertib) in mice
Ataxia Telangiectasia and Rad3-related (ATR) is a pivotal component of the DNA damage response and repair pathways that is activated in responses to cytotoxic cancer treatments. Several ATR inhibitors (ATRi) a...
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Article
Dose-dependent bioavailability and tissue distribution of the ATR inhibitor AZD6738 (ceralasertib) in mice
Ataxia telangiectasia and Rad3-related (ATR) initiates and regulates cellular responses to DNA damage, such as those caused by cancer treatments. Several ATR inhibitors (ATRi) are in clinical development inclu...
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Article
Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker
Carboplatin dose is calculated based on kidney function, commonly estimated with imperfect creatinine-based formulae. Iohexol is used to measure glomerular filtration rate (GFR) and allows calculation of a mor...
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Article
Toxicity, pharmacokinetics and metabolism of a novel inhibitor of IL-6-induced STAT3 activation
The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) promotes gene transcription involved in cancer, and its activation by IL-6 is found in head and neck squamous cell ...
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Article
Human mass balance study of TAS-102 using 14C analyzed by accelerator mass spectrometry
TAS-102 is an oral fluoropyrimidine prodrug composed of trifluridine (FTD) and tipiracil hydrochloride (TPI) in a 1:0.5 ratio. FTD is a thymidine analog, and it is degraded by thymidine phosphorylase (TP) to t...
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Article
Characterization of the metabolism of benzaldehyde dimethane sulfonate (NSC 281612, DMS612)
Benzaldehyde dimethane sulfonate (BEN, DMS612, NSC281612) is a bifunctional alkylating agent currently in clinical trials. We previously characterized the degradation products of BEN in plasma and blood. The c...
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In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of pyrazole-based small molecule inhibitors of Mdm2/4–p53 interaction
The interaction of p53 with its negative regulators Mdm2/4 has been widely studied (Khoury and Domling in Curr Pharm Des 18(30):4668–4678, 2012). In p53+/+ cells, expression of Mdm2/4 leads to p53 turnover, inhi...
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Plasma pharmacokinetics of the indenoisoquinoline topoisomerase I inhibitor, NSC 743400, in rats and dogs
NSC 743400 is a novel synthetic indenoisoquinoline analog under development as an anticancer agent. It is a potent topoisomerase I inhibitor with potential therapeutic advantages over FDA-approved camptothecin...
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Article
Effects of the aldehyde dehydrogenase inhibitor disulfiram on the plasma pharmacokinetics, metabolism, and toxicity of benzaldehyde dimethane sulfonate (NSC281612, DMS612, BEN) in mice
Benzaldehyde dimethane sulfonate (DMS612, NSC281612, BEN) is an alkylator with activity against renal cell carcinoma, currently in phase I trials. In blood, BEN is rapidly metabolized into its highly reactive ...
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Article
In vitro cytotoxicity, pharmacokinetics, tissue distribution, and metabolism of small-molecule protein kinase D inhibitors, kb-NB142-70 and kb-NB165-09, in mice bearing human cancer xenografts
Protein kinase D (PKD) mediates diverse biological responses including cell growth and survival. Therefore, PKD inhibitors may have therapeutic potential. We evaluated the in vitro cytotoxicity of two PKD inhi...
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Article
Formation of active products of benzaldehyde dimethane sulfonate (NSC 281612, DMS612) in human blood and plasma and their activity against renal cell carcinoma lines
Benzaldehyde dimethane sulfonate (BEN, DMS612, NSC281612) is an alkylating agent with activity against renal cell carcinoma and is being evaluated clinically. To support clinical trials, we developed an LC–MS/...
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Article
Plasma pharmacokinetics and oral bioavailability of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU), in mice
Cytidine drugs, such as gemcitabine, undergo rapid catabolism and inactivation by cytidine deaminase (CD). 3,4,5,6-tetrahydrouridine (THU), a potent CD inhibitor, has been applied preclinically and clinically ...
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Article
Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc–Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice
c-Myc is commonly activated in many human tumors and is functionally important in cellular proliferation, differentiation, apoptosis and cell cycle progression. The activity of c-Myc requires noncovalent inter...
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Article
Effect of antacid on imatinib absorption
Imatinib often causes gastric upset resulting in frequent co-administration of an antacid. Elevated gastric pH, delayed gastric emptying, or introduction of Mg2+/Al3+ could potentially change imatinib absorption,...
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Article
Plasma pharmacokinetics and oral bioavailability of 3,4,5,6-tetrahydrouridine, a cytidine deaminase inhibitor, in mice
Cytidine analogues such as cytosine arabinoside, gemcitabine, decitabine, 5-azacytidine, 5-fluoro-2′-deoxycytidine and 5-chloro-2′-deoxycytidine undergo rapid catabolism by cytidine deaminase (CD). 3,4,5,6-tet...
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Article
Tumor, tissue, and plasma pharmacokinetic studies and antitumor response studies of docetaxel in combination with 9-nitrocamptothecin in mice bearing SKOV-3 human ovarian xenografts
We evaluated the antitumor activity of two different schedules of docetaxel and 9-nitrocamptothecin (9NC) in mice bearing human SKOV-3 ovarian carcinoma xenografts and evaluated the plasma, tissue, and tumor d...
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Article
Concentrations of the DNA methyltransferase inhibitor 5-fluoro-2′-deoxycytidine (FdCyd) and its cytotoxic metabolites in plasma of patients treated with FdCyd and tetrahydrouridine (THU)
Although the DNA methyltransferase inhibitor 5-fluoro-2′-deoxycytidine (FdCyd), is being evaluated clinically, it must be combined with the cytidine deaminase inhibitor tetrahydrouridine (THU) to prevent rapid...
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Article
Disposition of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite in relation to ABC transporter genotypes
Purpose: The source of the pharmacokinetic variability of 9-nitrocamptothecin (9NC) and its 9-aminocamptothecin (9AC) metabolite is unknown. ATP-binding cassette (ABC) transporters have been reported to modulate ...
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Article
Clinical and pharmacokinetic study evaluating the effect of food on the disposition of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite in patients with solid tumors
Background: 9-Nitrocamptothecin (9NC) is an orally administered camptothecin analogue that has completed phase III trials for pancreatic cancer. In biological matrices, camptothecin analogues exist in equilibrium...
