The Experts below are selected from a list of 123 Experts worldwide ranked by ideXlab platform
Allan T. Van Oosterom - One of the best experts on this subject based on the ideXlab platform.
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phase i and pharmacokinetic study of halofuginone an oral Quinazolinone Derivative in patients with advanced solid tumours
European Journal of Cancer, 2006Co-Authors: Maja J A De Jonge, Denis Lacombe, Sandrine Marreaud, Shai Yarkoni, Jaap Verweij, D. Snyder, Takuhiro Yamaguchi, Herlinde Dumez, Cornelis J. A. Punt, Allan T. Van OosteromAbstract:PURPOSE: Halofuginone (tempostatin) is a synthetic Derivative of a Quinazolinone alkaloid showing anti-angiogenic, anti-metastatic and anti-proliferative effects in preclinical studies. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to study the pharmacokinetics (PKs) of halofuginone when administered once or twice daily orally to patients with advanced solid tumours. METHODS: Patients were treated with escalating doses of halofuginone at doses ranging from 0.5 to 3.5 mg/day. For pharmacokinetic analysis plasma sampling was performed during the first and second course and assayed using a validated high-performance liquid chromatographic assay with mass spectrometric detection. RESULTS: Twenty-four patients received a total of 106 courses. The 'acute' MTD was reached at 3.5 mg/day, with nausea, vomiting, and fatigue as DLT. The recommended dose for chronic administration was defined as 0.5mg/day with the requirement of 5HT3 antagonists to control nausea and vomiting considered as DLT. Several patients experienced bleeding complications on treatment with halofuginone in which a causal relationship could not be excluded. The PKs of halofuginone were linear over the dose range studied with a large interpatient variability. CONCLUSIONS: In this study the DLT of halofuginone was nausea, vomiting, and fatigue. The recommended dose for phase II studies of halofuginone is 0.5mg administered orally, once daily.
Amin I Kassis - One of the best experts on this subject based on the ideXlab platform.
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evaluation of chemical physical and biologic properties of tumor targeting radioiodinated Quinazolinone Derivative
Bioconjugate Chemistry, 2007Co-Authors: Ketai Wang, Agop M Kirichian, Ayman Al F Aowad, James S Adelstein, Amin I KassisAbstract:Our group is developing a novel technology, enzyme-mediated cancer imaging and therapy (EMCIT), that aims to entrap radioiodinated compounds within solid tumors for noninvasive tumor detection and therapy. In this approach, a water-soluble, radioiodinated prodrug is hydrolyzed in vivo to a highly water-insoluble compound by an enzyme overexpressed extracellularly by tumor cells. We have synthesized and characterized the water-soluble prodrug, 2-(2‘-phosphoryloxyphenyl)-6-[125I]iodo-4-(3H)-Quinazolinone [125I]5, which is readily hydrolyzed by alkaline phosphatase, an enzyme expressed by many tumor cell lines, to a water-insoluble drug, 2-(2‘-hydroxyphenyl)-6-[125I]iodo-4-(3H)-Quinazolinone [125I]1. In the course of our study, we discovered that ammonium 2-(2‘-phosphoryloxyphenyl)-6-tributylstannyl-4-(3H)-Quinazolinone, an intermediate in the radioiodination of the prodrug, exists as two isomers (3 and 4) whose radioiodination leads, respectively, to [125I]6 and [125I]5. These prodrugs have different in vit...
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synthesis and biologic evaluation of a radioiodinated Quinazolinone Derivative for enzyme mediated insolubilization therapy
Bioconjugate Chemistry, 2002Co-Authors: Ravi S Harapanhalli, Ketai Wang, James S Adelstein, Bassam A Dahman, Kai Chen, Amin I KassisAbstract:We have developed a new strategy that aims to concentrate therapeutic radionuclides within solid tumors. This approach, which we have named EMIT (enzyme-mediated insolubilization therapy), is a method for enzyme-dependent, site-specific, in vivo precipitation of a radioactive molecule (from a water-soluble precursor) within the extracellular space of solid tumors. The prodrug, ammonium 2-(2‘-phosphoryloxyphenyl)-6-iodo-4-(3H)-Quinazolinone, labeled with iodine-125 (125IPD) and its authentic compound labeled with iodine-127 (IPD) have been synthesized, purified, and characterized. The alkaline phosphatase (ALP)-mediated conversion of these water-soluble nonfluorescent prodrugs to the water-insoluble fluorescent species, iodine-125-labeled 2-(2‘-hydroxyphenyl)-6-iodo-4-(3H)-Quinazolinone (125ID) and its iodine-127-labeled Derivative (ID), has been demonstrated in vitro. Biodistribution studies in mice indicate that both 125IPD and 125ID are minimally retained by most tissues and organs. In addition, followi...
Maja J A De Jonge - One of the best experts on this subject based on the ideXlab platform.
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phase i and pharmacokinetic study of halofuginone an oral Quinazolinone Derivative in patients with advanced solid tumours
European Journal of Cancer, 2006Co-Authors: Maja J A De Jonge, Denis Lacombe, Sandrine Marreaud, Shai Yarkoni, Jaap Verweij, D. Snyder, Takuhiro Yamaguchi, Herlinde Dumez, Cornelis J. A. Punt, Allan T. Van OosteromAbstract:PURPOSE: Halofuginone (tempostatin) is a synthetic Derivative of a Quinazolinone alkaloid showing anti-angiogenic, anti-metastatic and anti-proliferative effects in preclinical studies. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to study the pharmacokinetics (PKs) of halofuginone when administered once or twice daily orally to patients with advanced solid tumours. METHODS: Patients were treated with escalating doses of halofuginone at doses ranging from 0.5 to 3.5 mg/day. For pharmacokinetic analysis plasma sampling was performed during the first and second course and assayed using a validated high-performance liquid chromatographic assay with mass spectrometric detection. RESULTS: Twenty-four patients received a total of 106 courses. The 'acute' MTD was reached at 3.5 mg/day, with nausea, vomiting, and fatigue as DLT. The recommended dose for chronic administration was defined as 0.5mg/day with the requirement of 5HT3 antagonists to control nausea and vomiting considered as DLT. Several patients experienced bleeding complications on treatment with halofuginone in which a causal relationship could not be excluded. The PKs of halofuginone were linear over the dose range studied with a large interpatient variability. CONCLUSIONS: In this study the DLT of halofuginone was nausea, vomiting, and fatigue. The recommended dose for phase II studies of halofuginone is 0.5mg administered orally, once daily.
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Phase I and pharmacokinetic study of halofuginone, an oral Quinazolinone Derivative in patients with advanced solid tumours.
'Elsevier BV', 2006Co-Authors: Maja J A De Jonge, Dumez H., Verweij J., Yarkoni S., Snyder D., Lacombe D., Marreaud S., Yamaguchi T., Punt C.j.a., Oosterom A. VanAbstract:Item does not contain fulltextPURPOSE: Halofuginone (tempostatin) is a synthetic Derivative of a Quinazolinone alkaloid showing anti-angiogenic, anti-metastatic and anti-proliferative effects in preclinical studies. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to study the pharmacokinetics (PKs) of halofuginone when administered once or twice daily orally to patients with advanced solid tumours. METHODS: Patients were treated with escalating doses of halofuginone at doses ranging from 0.5 to 3.5 mg/day. For pharmacokinetic analysis plasma sampling was performed during the first and second course and assayed using a validated high-performance liquid chromatographic assay with mass spectrometric detection. RESULTS: Twenty-four patients received a total of 106 courses. The 'acute' MTD was reached at 3.5 mg/day, with nausea, vomiting, and fatigue as DLT. The recommended dose for chronic administration was defined as 0.5mg/day with the requirement of 5HT3 antagonists to control nausea and vomiting considered as DLT. Several patients experienced bleeding complications on treatment with halofuginone in which a causal relationship could not be excluded. The PKs of halofuginone were linear over the dose range studied with a large interpatient variability. CONCLUSIONS: In this study the DLT of halofuginone was nausea, vomiting, and fatigue. The recommended dose for phase II studies of halofuginone is 0.5mg administered orally, once daily
Ketai Wang - One of the best experts on this subject based on the ideXlab platform.
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evaluation of chemical physical and biologic properties of tumor targeting radioiodinated Quinazolinone Derivative
Bioconjugate Chemistry, 2007Co-Authors: Ketai Wang, Agop M Kirichian, Ayman Al F Aowad, James S Adelstein, Amin I KassisAbstract:Our group is developing a novel technology, enzyme-mediated cancer imaging and therapy (EMCIT), that aims to entrap radioiodinated compounds within solid tumors for noninvasive tumor detection and therapy. In this approach, a water-soluble, radioiodinated prodrug is hydrolyzed in vivo to a highly water-insoluble compound by an enzyme overexpressed extracellularly by tumor cells. We have synthesized and characterized the water-soluble prodrug, 2-(2‘-phosphoryloxyphenyl)-6-[125I]iodo-4-(3H)-Quinazolinone [125I]5, which is readily hydrolyzed by alkaline phosphatase, an enzyme expressed by many tumor cell lines, to a water-insoluble drug, 2-(2‘-hydroxyphenyl)-6-[125I]iodo-4-(3H)-Quinazolinone [125I]1. In the course of our study, we discovered that ammonium 2-(2‘-phosphoryloxyphenyl)-6-tributylstannyl-4-(3H)-Quinazolinone, an intermediate in the radioiodination of the prodrug, exists as two isomers (3 and 4) whose radioiodination leads, respectively, to [125I]6 and [125I]5. These prodrugs have different in vit...
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synthesis and biologic evaluation of a radioiodinated Quinazolinone Derivative for enzyme mediated insolubilization therapy
Bioconjugate Chemistry, 2002Co-Authors: Ravi S Harapanhalli, Ketai Wang, James S Adelstein, Bassam A Dahman, Kai Chen, Amin I KassisAbstract:We have developed a new strategy that aims to concentrate therapeutic radionuclides within solid tumors. This approach, which we have named EMIT (enzyme-mediated insolubilization therapy), is a method for enzyme-dependent, site-specific, in vivo precipitation of a radioactive molecule (from a water-soluble precursor) within the extracellular space of solid tumors. The prodrug, ammonium 2-(2‘-phosphoryloxyphenyl)-6-iodo-4-(3H)-Quinazolinone, labeled with iodine-125 (125IPD) and its authentic compound labeled with iodine-127 (IPD) have been synthesized, purified, and characterized. The alkaline phosphatase (ALP)-mediated conversion of these water-soluble nonfluorescent prodrugs to the water-insoluble fluorescent species, iodine-125-labeled 2-(2‘-hydroxyphenyl)-6-iodo-4-(3H)-Quinazolinone (125ID) and its iodine-127-labeled Derivative (ID), has been demonstrated in vitro. Biodistribution studies in mice indicate that both 125IPD and 125ID are minimally retained by most tissues and organs. In addition, followi...
Guoli Shen - One of the best experts on this subject based on the ideXlab platform.
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a fluorescent chemical sensor for fe3 based on blocking of intramolecular proton transfer of a Quinazolinone Derivative
Talanta, 2007Co-Authors: Xiaobing Zhang, Guo Cheng, Weijun Zhang, Guoli ShenAbstract:Abstract In this paper, 2-(2′-hydroxy-phenyl)-4(3H)-Quinazolinone (HPQ), a typical compound that exhibits excited state intramolecular proton transfer (ESIPT) reaction and possesses good photophysical properties, is synthesized and used as fluoroionophore for Fe 3+ sensitive optochemical sensor. The decrease of fluorescence intensity of HPQ membrane upon the addition of Fe 3+ was attributed to the blocking of ESIPT reactions of HPQ and quenching its fluorescence. The effect of the composition of the sensing membrane was studied, and experimental conditions were optimized. The sensor shows a linear response toward Fe 3+ in the concentration range of 7.1 × 10 −7 M to 1.4 × 10 −4 M with a limit of detection of 8.0 × 10 −8 M, and a working pH range from 2.5 to 4.5. It shows excellent selectivity for Fe 3+ over a large number of cations such as alkali, alkaline earth and transitional metal ions. The proposed sensor is applied to the determination of the content of iron ions in pharmaceutical preparations samples with satisfactory results.
