Detail of "796967-16-3"

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A high-throughput liquid chromatography/tandem mass spectrometry method for simultaneous quantification of a hydrophobic drug candidate and its hydrophilic metabolite in human urine with a fully automated liquid/liquid extraction

All Rights Reserved. A high-throughput liquid chromatography/tandem mass spectrometry method for simultaneous quantification of a hydrophobic drug candidate and its hydrophilic metabolite in human urine with a fully automated liquid/liquid extraction. Wang, Perry G.; Zhang, Jun; Gage, Eric M.; Schmidt, Jeffrey M.; Rodila, Ramona C.; Ji, Qin C.; El-Shourbagy, Tawakol A. (Department of Drug Analysis, Abbott Laboratories, Abbott Park, IL 60064, USA). Rapid Communications in Mass Spectrometry, 20(22), 3456-3464 (English) 2006 John Wiley & Sons Ltd. CODEN: RCMSEF. ISSN: 0951-4198. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) ABT-869 (A-741439) is an investigational new drug candidate under development by Abbott Labs. ABT-869 is hydrophobic, but is oxidized in the body to A-849529, a hydrophilic metabolite that includes both carboxyl and amino groups. Poor soly. of ABT-869 in aq. matrix causes simultaneous anal. of both ABT-869 and its metabolite within the same extn. and injection to be extremely difficult in human urine. In this paper, a high-performance liq. chromatog./tandem mass spectrometry (HPLC/MS/MS) method was developed and validated for high-speed simultaneous quantitation of the hydrophobic ABT-869 and its hydrophilic metabolite, A-849529, in human urine. The deuterated internal stds., A-741439D4 and A-849529D4, were used in this method. The disparate properties of the two analytes were mediated by treating samples with acetonitrile, adjusting pH with an extn. buffer, and optimizing the extn. solvent and mobile phase compn. For a 100 mL urine sample vol., the lower limit of quantitation was approx. 1 ng/mL for both ABT-869 and A-849529. The calibration curve was linear from 1.09 to 595.13 ng/mL for ABT-869, and 1.In this experiment, several chemicals are used like 819058-88-3 and 796967-16-3 10 to 600.48 ng/mL for A-849529 (r2 > 0.9975 for both ABT-869 and A-849529). Because the method employs simultaneous quantification, high throughput is achieved despite the presence of both a hydrophobic analyte and its hydrophilic metabolite in human urine. .

Hypoxia-Inducible Factor-1 Inhibition in Combination with Temozolomide Treatment Exhibits Robust Antitumor Efficacy In vivo

All Rights Reserved. Hypoxia-Inducible Factor-1 Inhibition in Combination with Temozolomide Treatment Exhibits Robust Antitumor Efficacy In vivo. Li, Leiming; Lin, Xiaoyu; Shoemaker, Alex R.; Albert, Daniel H.; Fesik, Stephen W.; Shen, Yu (Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, USA). Clinical Cancer Research, 12(15), 4747-4754 (English) 2006 American Association for Cancer Research. CODEN: CCREF4. ISSN: 1078-0432. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Purpose: Inhibiting hypoxia-inducible factor-1 (HIF-1) represents a unique mechanism for cancer therapy. It is conceived that HIF-1 inhibitors may synergize with many classes of cancer therapeutic agents, such as angiogenesis inhibitors and cytotoxic drugs, to achieve a more robust tumor response. 796967-16-3 and 154-93-8 which are cas registry numbers are also used here. However, these hypotheses have not been rigorously tested in tumor models in vivo. The present study was carried out to evaluate the antitumor efficacy of combining HIF-1 inhibition with angiogenesis inhibitors or cytotoxic agents. Exptl. Design: Using a D54MG-derived tumor model that allows knockdown of HIF-1a on doxycycline treatment, we examd. the tumor responses to chemotherapeutic agents, including the angiogenesis inhibitor ABT-869 and cytotoxic agents 1,3-bis(2-chloroethyl)-1-nitrosourea and temozolomide, in the presence or absence of an intact HIF-1 pathway. Results: Surprisingly, inhibiting HIF-1 in tumors treated with the angiogenesis inhibitor ABT-869 did not produce much added benefit compared with ABT-869 treatment alone, suggesting that the combination of an angiogenesis inhibitor with a HIF-1 inhibitor may not be a robust therapeutic regimen. In contrast, the cytotoxic drug temozolomide, when used in combination with HIF-1a knockdown, exhibited a superadditive and likely synergistic therapeutic effect compared with the monotherapy of either treatment alone in the D54MG glioma model. Conclusions: Our results show that the DNA alkylating agent temozolomide exhibits robust antitumor efficacy when used in combination with HIF-1 inhibition in D54MG-derived tumors, suggesting that the combination of temozolomide with HIF-1 inhibitors might be an effective regimen for cancer therapy. In addn., our results also show that the RNA interference-based inducible knockdown model can be a valuable platform for further evaluation of the combination treatment of other cancer therapeutics with HIF-1 inhibition. .