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Featured researches published by Amy Wu.


Journal of Pharmacology and Experimental Therapeutics | 2011

Physiological and Molecular Characterization of Aristolochic Acid Transport by the Kidney

Kathleen G. Dickman; Douglas H. Sweet; Radha Bonala; Tapan Ray; Amy Wu

Consumption of herbal medicines derived from Aristolochia plants is associated with a progressive tubulointerstitial disease known as aristolochic acid (AA) nephropathy. The nephrotoxin produced naturally by these plants is AA-I, a nitrophenanthrene carboxylic acid that selectively targets the proximal tubule. This nephron segment is prone to toxic injury because of its role in secretory elimination of drugs and other xenobiotics. Here, we characterize the handling of AA-I by membrane transporters involved in renal organic anion transport. Uptake assays in heterologous expression systems identified murine organic anion transporters (mOat1, mOat2, and mOat3) as capable of mediating transport of AA-I. Kinetic analyses showed that all three transporters have an affinity for AA-I in the submicromolar range and thus are likely to operate at toxicologically relevant concentrations in vivo. Structure-activity relationships revealed that the carboxyl group is critical for high-affinity interaction of AA-I with mOat1, mOat2, and mOat3, whereas the nitro group is required only by mOat1. Furthermore, the 8-methoxy group, although essential for toxicity, was not requisite for transport. Mouse renal cortical slices avidly accumulated AA-I, achieving slice-to-medium concentration ratios >10. Uptake by slices was sensitive to known mOat1 and mOat3 substrates and the organic anion transport inhibitor probenecid, which also blocked the production of DNA adducts formed with reactive intracellular metabolites of AA-I. Taken together, these findings indicate that OAT family members mediate high-affinity transport of AA-I and may be involved in the site-selective toxicity and renal elimination of this nephrotoxin.


Journal of Labelled Compounds and Radiopharmaceuticals | 2000

Palladium-catalyzed aryl cyanations with [14C]KCN: Synthesis of 14C-labelled fadrozole, a potent aromatase inhibitor

Alban J. Allentoff; Bohdan Markus; Timothy Duelfer; Amy Wu; Lawrence Jones; Grazyna Ciszewska; Tapan Ray

The potent aromatase inhibitor [14C]Fadrozole (1), was prepared in a single radiosynthetic step via a palladium(0)-catalyzed cyanation of the imidazole-containing aryl iodide 2b with [14C]KCN. Attempted preparation of 2b by metal-halogen interchange of the corresponding aryl bromide 2a with tert-butyl lithium followed by quenching with iodine afforded only the imidazole iodide 5 via disproportionation of the intermediate anion. The desired precursor was finally synthesized through a three-step sequence beginning with the alkylation of known imidazole derivative 8 with 4-iodobenzylbromide. This alkylation product was treated with thionyl chloride to convert a side chain hydroxyl to its corresponding primary chloride 10. Cyclization of chloride 10 using LDA/TMEDA gave the desired aryl iodide 2b. While initial attempts at the palladium(0)-catalyzed cyanation of 2b with unlabelled KCN in THF at reflux gave modest yields of Fadrozole, the reaction with [14C]KCN afforded only trace amounts of [14C]Fadrozole. By including Copper(I) iodide as a co-catalyst and using deoxygenated THF, the palladium(0)-catalyzed cyanation of 2b gave [14C]Fadrozole in 39% radiochemical yield with >99% radiochemical purity. Copyright


Journal of Labelled Compounds and Radiopharmaceuticals | 2014

Proton exchange reactions in isotope chemistry (II) synthesis of stable isotope‐labeled LCQ908

Zhigang Jian; Tapan Ray; Amy Wu; Lawrence Jones; Ry R. Forseth

The proton exchange reaction was applied to the preparation of stable isotope-labeled LCQ908. For this synthesis, a suitable intermediate with protons alpha to a carbonyl group was first subjected to the H-D exchange reaction; subsequent coupling of a carbonyl group with [(13)C2 ]triethyl phosphonoacetate, followed by hydrogenation and hydrolysis, led to the stable labeled compound. Incorporation of two carbon-13 atoms in the molecule eliminated the presence of undesired M+0.


Journal of Chromatography B | 2007

Simultaneous determination of ribavirin and ribavirin base in monkey plasma by high performance liquid chromatography with tandem mass spectrometry

Wenkui Li; Suyi Luo; Shaoyong Li; Lawrence V. Athill; Amy Wu; Tapan Ray; Wei Zhou; June Ke; Harold T. Smith; Francis L.S. Tse


Journal of Labelled Compounds and Radiopharmaceuticals | 2007

Synthesis of radio- and stable-labelled LAF237(Galvus, Vildagliptin)†

Grazyna Ciszewska; Alban Allentoff; Lawrence Jones; Amy Wu; Tapan Ray


Journal of Labelled Compounds and Radiopharmaceuticals | 2007

Synthesis and analysis of tritiated camptothecin analogs with iridium‐mediated 3H exchange

Tapan Ray; Amy Wu; Alban Allentoff


Journal of Labelled Compounds and Radiopharmaceuticals | 2007

Convenient and efficient tritiation of aristolochic acid I (AAI) and aristolochic acid II (AAII) with tritiated water

Tapan Ray; Amy Wu; Alban Allentoff


Journal of Labelled Compounds and Radiopharmaceuticals | 2007

Synthesis and analysis of (3H) salmon calcitonin ((3H)SMC021)

Grazyna Ciszewska; Alban Allentoff; Amy Wu; Tapan Ray


Journal of Labelled Compounds and Radiopharmaceuticals | 2012

Proton exchange reactions in isotope chemistry (I)

Zhigang Jian; Tapan Ray; Amy Wu; Lawrence Jones


Journal of Labelled Compounds and Radiopharmaceuticals | 2006

An improved synthesis of isotope labeled 6‐hydroxychlorzoxazone

Zhigang Jian; Tapan Ray; Amy Wu; Lawrence Jones

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