| dc.identifier.uri | http://hdl.handle.net/1951/59941 | |
| dc.identifier.uri | http://hdl.handle.net/11401/71478 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | Over the past decades, chemotherapy has transitioned to an age of
"targeted therapy." The development of Gleevec (Novartis) and Tarceva (Genentech
and OSI Pharmaceuticals) has revolutionized the treatment of certain cancers, such as chronic
myelogenous leukemia (CML), non-small cell lung cancer (NSCLC) and pancreatic cancer. Gleevec
specifically targets the cancer cell-overexpressed Abl tyrosine kinase, and Tarceva targets
the epidermal growth factor receptor that is mutated in different types of cancers. However,
the use of these modern targeted-therapies is limited to specific cancer types. Therefore,
considerable efforts have been made to find cancer-specific markers which can be exploited
for tumor-specific delivery of more traditional chemotherapeutic drugs. A promising approach
along this line is the development of tumor-targeting drug conjugates, which consists of one
or multiple cytotoxic drugs (warheads) connected to a tumor-targeting module (TTM) via
cleavable covalent bonds or cleavable linkers. The drug conjugates have been designed to
remain inactive until they are specifically delivered to the tumor site, guided by the TTM
and internalized, where the warhead is released from the carrier, restoring its original
activity. New-generation taxoids have been developed by the Ojima laboratory via the
Β-lactam synthon method. These taxoids show orders of magnitude greater potency in a
number of cancer cell lines compared to the parent compound paclitaxel. Thus, new-generation
taxoids are promising candidates as warheads for tumor-targeting drug conjugates.
Accordingly, a number of new-generation taxoid-based drug conjugates have been developed that
contain polyunsaturated fatty acids (PUFAs), vitamins and monoclonal antibodies (mAbs) as
TTM. The synthesis and biological evaluation of these novel drug conjugates will be
discussed. | |
| dcterms.available | 2013-05-22T17:35:56Z | |
| dcterms.available | 2015-04-24T14:47:42Z | |
| dcterms.contributor | Fowler, Frank W.Parker, | en_US |
| dcterms.contributor | Ojima, Iwao | en_US |
| dcterms.creator | Zuniga, Edison S. | |
| dcterms.dateAccepted | 2013-05-22T17:35:56Z | |
| dcterms.dateAccepted | 2015-04-24T14:47:42Z | |
| dcterms.dateSubmitted | 2013-05-22T17:35:56Z | |
| dcterms.dateSubmitted | 2015-04-24T14:47:42Z | |
| dcterms.description | Department of
Chemistry | en_US |
| dcterms.extent | 432 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/1951/59941 | |
| dcterms.identifier | Zuniga_grad.sunysb_0771E_10892 | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/71478 | |
| dcterms.issued | 2012-05-01 | |
| dcterms.language | en_US | |
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Previous issue date: 1 | en |
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Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Anticancer agent, Cytotoxicity, Drug conjugate, Taxoid, Tumor-targeted drug
delivery | |
| dcterms.subject | Organic chemistry | |
| dcterms.title | Design, synthesis and biological
evaluation of new-generation taxoid-based tumor-targeting drug conjugates | |
| dcterms.type | Dissertation | |
