Ge Healthcare UK Limited

Ge Healthcare Limited

Cancer Research Technology Limited

Rahman Aziz Ismail

Nicholas Thomas

Simon Laurence John Stubbs

Richard Martin West

John Gerard Whateley

Peter Gordon Laughton

Michael John Francis

Simon L Stubbs

Anne Elizabeth Jones

Ian D Goodyer

Gerard Bernard O'Beirne

Adrian Cushing

Jonathon Noe Pines

Jonathan Mark Kendall

Disclosed are nitro-substituted squaraine reporter dyes and methods using such dyes for detecting nitroreductase enzyme activity and nitroreductase gene expression in cellular assays. The dyes are of the structure: in which Zand Zindependently represent a phenyl or a naphthyl ring system; X and Y are selected from oxygen, sulphur, &#x2014;CH&#x2550;CH&#x2014; and the group: Rand Rare selected from C-Calkyl, &#x2014;(CH)&#x2014;P, &#x2014;{(CH)&#x2014;O}&#x2014;Rand group W; where P is selected from COOR, SOand OH, W is mono- or di-substituted nitrobenzyl, Ris methyl or ethyl, Ris selected from H, C-Calkyl and CHOC(O)R, where Ris methyl, or t-butyl, n is an integer from 1 to 10, and p is an integer from 1 to 3; Rand Rare selected from hydrogen, NO, halogen, SO, C-Calkoxy and &#x2014;(CH)&#x2014;COOR; where Ris hereinbefore defined and m is 0 or an integer from 1 to 5; Ris C-Calkyl optionally substituted with COOR, SO, or OH; where Ris hereinbefore defined; and at least one of groups R, R, Rand Rcomprises at least one NOgroup. Also provided are methods for screening for a test agent whose effect upon nitroreductase enzyme activity and nitroreductase gene expression is to be determined.

Method and reagent for measuring nitroreductase enzyme activity

The present invention relates to compounds useful for measuring aromatase activity. The invention further provides methods for measuring aromatase activity and for screening test agents which modulate aromatase activity. A kit is also provided for use in such screening methods.

Method for measuring aromatase activity

The present invention relates to a cytochrome c-reporter fusion protein construct comprising a modified cytochrome c protein which targets the mitochondria and has a reduced ability to induce apoptosis in a living cell. The invention also relates to nucleic acid constructs encoding such protein fusions and cells stably transfected with such constructs. The stably transfected cells of the invention can be used in assays to detect apoptosis.

Cytochrome c protein and assay

The invention provides a novel, non-destructive and dynamic process for determining the cell cycle position of living cells. The invention also provides DNA constructs, and cell lines containing such constructs, that exhibit activation and deactivation of a detectable reporter molecule in a cell cycle specific manner. The invention thus allows greater precision in determining cell cycle phase status than existing techniques and further provides a method for continuous monitoring of cell cycle progression in individual cells.

Method for determining cell cycle position

Disclosed is a method for the measurement of a cellular process, or for the measurement of the effect of a test compound on a cellular process, in one or more different populations of cells. The method comprises providing separate samples of one or more different populations of cells adhering to support particles, the support particles comprising a scintillant substance and being adapted for cell growth. In one embodiment, different samples of cells are introduced into separate reaction vessels in a fluid medium, together with a reagent labelled with a radioisotope, in the presence or the absence of the test compound, under conditions so as to cause a portion of said radiolabelled reagent to become associated with the cells. In another embodiment, multiparameter analysis may be performed to determine the effect of a test compound on a cellular process using two or more different cell populations present in the same well. Measurement of the cellular process, or the effect of a test compound on a cellular process may be made by detecting light emission from the scintillant particles caused by radioactive decay of the radioisotope.

Support and method for cell based assays

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Cardiff, United Kingdom

Rahman Aziz Ismail