- Towards aspirin-inspired self-immolating molecules which target the cyclooxygenases
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Cyclooxygenases (COXs) are enzymes that play a vital role in the inflammatory cascade through the generation of prostaglandins. Their over-expression has been implicated in numerous diseases. In particular, over-expression of COX-2 has been shown to be a predictive biomarker for progression of pre-malignant lesions towards invasive cancer in various tissues. This makes the early detection of COX-2 expressing lesions of high clinical relevance. Herein we describe the development of the first self-immolating trigger which targets COXs. We incorporated our trigger design into 2 activatable fluorogenic probes and demonstrated COX-specific activation in vitro. Experimental data revealed probe activation was likely caused by solvent-exposed amino acids on the surface of the COXs. Overall, the probes reported here mark the first step towards developing self-immolating imaging/therapeutic agents targeted to specific COXs.
- Drake, Christopher R.,Estévez-Salmerón, Luis,Gascard, Philippe,Shen, Yang,Tlsty, Thea D.,Jones, Ella F.
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p. 11078 - 11086
(2015/11/25)
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- HYPOTENSIVE BENZOXATHIOLE PYRROLIDINES
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Compounds of the formula STR1 and the pharmaceutically acceptable, nontoxic, acid addition salts thereof, whereinR 1 and R 2 are each independently--H, lower alkyl, or cycloalkyl, with the proviso that R 1 and R 2 cannot both be--H or cycloalkyl at
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