Inhibition of Prostate Cancer via Inhibition of Peptidylglycine α-Amidating Monooxygenase (PAM)
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University of Toledo / OhioLINK
2011
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=toledo1302200866 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-toledo13022008662021-08-03T06:07:48Z Inhibition of Prostate Cancer via Inhibition of Peptidylglycine α-Amidating Monooxygenase (PAM) Bearss, Nicole R. Biology Pharmaceuticals Pharmacology PAM hormone refractory prostate cancer peptidylglycine alpha-amidating monooxygenase DU145 prostate cancer <p>Prostate cancer (CaP) is a widespread and costly disease. Hormone-dependent CaP can be treated with hormone-deprivation therapy, often resulting in the development of a hormone-independent stage via neuroendocrine differentiation, which currently has no effective treatments. Differentiated hormone-independent CaP also can express peptidyglycine α-amidating monooxygenase (PAM), which amidates peptides that have Gly as their C-terminus resulting in a much more potent activity of the peptide. Several PAM substrates are cellular growth signals. Because hormone-independent CaP often express PAM, and PAM activates many growth factors, inhibiting PAM could result in decreased cell growth and therefore PAM inhibitors may be effective treatments for hormone-independent CaP.</p><p>A series of PAM substrate-like inhibitors was synthesized. The potencies of these agents were determined by <i>in vitro</i> tests against PAM from cell culture media and cellular extracts. These inhibitors were also tested against PAM-dependent DU145 CaP cell growth, and one of these inhibitors, CD3-246, emerged as our lead PAM inhibiting agent. <i>In vivo</i> studies determined that CD3-246 inhibited the growth of implanted CaP xenographs in mice. In conclusion, CD3-246 appears to represent a potential novel treatment for hormone-independent CaP.</p> 2011-05-17 English text University of Toledo / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=toledo1302200866 http://rave.ohiolink.edu/etdc/view?acc_num=toledo1302200866 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biology Pharmaceuticals Pharmacology PAM hormone refractory prostate cancer peptidylglycine alpha-amidating monooxygenase DU145 prostate cancer |
| spellingShingle |
Biology Pharmaceuticals Pharmacology PAM hormone refractory prostate cancer peptidylglycine alpha-amidating monooxygenase DU145 prostate cancer Bearss, Nicole R. Inhibition of Prostate Cancer via Inhibition of Peptidylglycine α-Amidating Monooxygenase (PAM) |
| author |
Bearss, Nicole R. |
| author_facet |
Bearss, Nicole R. |
| author_sort |
Bearss, Nicole R. |
| title |
Inhibition of Prostate Cancer via Inhibition of Peptidylglycine α-Amidating Monooxygenase (PAM) |
| title_short |
Inhibition of Prostate Cancer via Inhibition of Peptidylglycine α-Amidating Monooxygenase (PAM) |
| title_full |
Inhibition of Prostate Cancer via Inhibition of Peptidylglycine α-Amidating Monooxygenase (PAM) |
| title_fullStr |
Inhibition of Prostate Cancer via Inhibition of Peptidylglycine α-Amidating Monooxygenase (PAM) |
| title_full_unstemmed |
Inhibition of Prostate Cancer via Inhibition of Peptidylglycine α-Amidating Monooxygenase (PAM) |
| title_sort |
inhibition of prostate cancer via inhibition of peptidylglycine α-amidating monooxygenase (pam) |
| publisher |
University of Toledo / OhioLINK |
| publishDate |
2011 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1302200866 |
| work_keys_str_mv |
AT bearssnicoler inhibitionofprostatecancerviainhibitionofpeptidylglycineaamidatingmonooxygenasepam |
| _version_ |
1719431418352762880 |