Evaluation Of Toxicity, Pharmacokinetic And Clastogenicity Profile Of Ethyl 2-[4[(Piperidin-1-yl) Phenyl]-1h-benzimidazole-5-carboxylate (Bzd9l1), Novel Sirtuin Inhibitor

The mammalian sirtuins (SIRTs) have been linked to various diseases including cancer, diabetes, neurodegenerative and cardiovascular diseases. Thus, SIRTs are attractive targets for the development of pharmaceuticals. The lack of potential SIRT inhibitors in cancer clinical trials highlights the nee...

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Main Author: Lee, Yeuan Ting
Format: Thesis
Language:English
Published: 2022
Subjects:
Online Access:http://eprints.usm.my/59372/
http://eprints.usm.my/59372/1/LEE%20YEUAN%20TING%20-%20TESIS24.pdf
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author Lee, Yeuan Ting
author_facet Lee, Yeuan Ting
author_sort Lee, Yeuan Ting
building USM Institutional Repository
collection Online Access
description The mammalian sirtuins (SIRTs) have been linked to various diseases including cancer, diabetes, neurodegenerative and cardiovascular diseases. Thus, SIRTs are attractive targets for the development of pharmaceuticals. The lack of potential SIRT inhibitors in cancer clinical trials highlights the need to develop a potent SIRT modulator as an anti-cancer therapeutic. Studies in the lab have highlighted the capability of a lead sirtuin inhibitor (BZD9L1) to reduce colorectal tumour growth in vitro and in vivo by modulating different cancer pathways in colorectal cancer with different mutation profiles. Also, synergistic effects of BZD9L1 in in vitro assays and tumour xenograft study when used in adjunct with 5- Fluorouracil (5-FU) further support the promising therapeutic effects of BZD9L1 as anticancer regime. Nevertheless, the toxicology profile of this compound remains unknown. To our knowledge, no prior work has reported the regulation of SIRTs in the liver and kidney by a small molecule inhibitor in a drug toxicity study. Therefore, this project aims to determine the toxicology, molecular regulation of toxicity, pharmacokinetics and clastogenicity profiles of BZD9L1 in in vitro or in vivo models
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institution Universiti Sains Malaysia
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language English
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spelling usm-593722023-09-13T05:02:21Z http://eprints.usm.my/59372/ Evaluation Of Toxicity, Pharmacokinetic And Clastogenicity Profile Of Ethyl 2-[4[(Piperidin-1-yl) Phenyl]-1h-benzimidazole-5-carboxylate (Bzd9l1), Novel Sirtuin Inhibitor Lee, Yeuan Ting R5-920 Medicine (General) The mammalian sirtuins (SIRTs) have been linked to various diseases including cancer, diabetes, neurodegenerative and cardiovascular diseases. Thus, SIRTs are attractive targets for the development of pharmaceuticals. The lack of potential SIRT inhibitors in cancer clinical trials highlights the need to develop a potent SIRT modulator as an anti-cancer therapeutic. Studies in the lab have highlighted the capability of a lead sirtuin inhibitor (BZD9L1) to reduce colorectal tumour growth in vitro and in vivo by modulating different cancer pathways in colorectal cancer with different mutation profiles. Also, synergistic effects of BZD9L1 in in vitro assays and tumour xenograft study when used in adjunct with 5- Fluorouracil (5-FU) further support the promising therapeutic effects of BZD9L1 as anticancer regime. Nevertheless, the toxicology profile of this compound remains unknown. To our knowledge, no prior work has reported the regulation of SIRTs in the liver and kidney by a small molecule inhibitor in a drug toxicity study. Therefore, this project aims to determine the toxicology, molecular regulation of toxicity, pharmacokinetics and clastogenicity profiles of BZD9L1 in in vitro or in vivo models 2022-05 Thesis NonPeerReviewed application/pdf en http://eprints.usm.my/59372/1/LEE%20YEUAN%20TING%20-%20TESIS24.pdf Lee, Yeuan Ting (2022) Evaluation Of Toxicity, Pharmacokinetic And Clastogenicity Profile Of Ethyl 2-[4[(Piperidin-1-yl) Phenyl]-1h-benzimidazole-5-carboxylate (Bzd9l1), Novel Sirtuin Inhibitor. PhD thesis, Universiti Sains Malaysia.
spellingShingle R5-920 Medicine (General)
Lee, Yeuan Ting
Evaluation Of Toxicity, Pharmacokinetic And Clastogenicity Profile Of Ethyl 2-[4[(Piperidin-1-yl) Phenyl]-1h-benzimidazole-5-carboxylate (Bzd9l1), Novel Sirtuin Inhibitor
title Evaluation Of Toxicity, Pharmacokinetic And Clastogenicity Profile Of Ethyl 2-[4[(Piperidin-1-yl) Phenyl]-1h-benzimidazole-5-carboxylate (Bzd9l1), Novel Sirtuin Inhibitor
title_full Evaluation Of Toxicity, Pharmacokinetic And Clastogenicity Profile Of Ethyl 2-[4[(Piperidin-1-yl) Phenyl]-1h-benzimidazole-5-carboxylate (Bzd9l1), Novel Sirtuin Inhibitor
title_fullStr Evaluation Of Toxicity, Pharmacokinetic And Clastogenicity Profile Of Ethyl 2-[4[(Piperidin-1-yl) Phenyl]-1h-benzimidazole-5-carboxylate (Bzd9l1), Novel Sirtuin Inhibitor
title_full_unstemmed Evaluation Of Toxicity, Pharmacokinetic And Clastogenicity Profile Of Ethyl 2-[4[(Piperidin-1-yl) Phenyl]-1h-benzimidazole-5-carboxylate (Bzd9l1), Novel Sirtuin Inhibitor
title_short Evaluation Of Toxicity, Pharmacokinetic And Clastogenicity Profile Of Ethyl 2-[4[(Piperidin-1-yl) Phenyl]-1h-benzimidazole-5-carboxylate (Bzd9l1), Novel Sirtuin Inhibitor
title_sort evaluation of toxicity, pharmacokinetic and clastogenicity profile of ethyl 2-[4[(piperidin-1-yl) phenyl]-1h-benzimidazole-5-carboxylate (bzd9l1), novel sirtuin inhibitor
topic R5-920 Medicine (General)
url http://eprints.usm.my/59372/
http://eprints.usm.my/59372/1/LEE%20YEUAN%20TING%20-%20TESIS24.pdf