東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

An Integrative in Silico Approach to...

Gessner, Christopher.

FindBook

Google Book

Amazon

博客來

An Integrative in Silico Approach to Preclinical Drug Discovery.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	An Integrative in Silico Approach to Preclinical Drug Discovery./
作者:	Gessner, Christopher.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2023,
面頁冊數:	106 p.
附註:	Source: Dissertations Abstracts International, Volume: 84-12, Section: B.
Contained By:	Dissertations Abstracts International84-12B.
標題:	Bioinformatics. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30528558
ISBN:	9798379764609

An Integrative in Silico Approach to Preclinical Drug Discovery.
Gessner, Christopher.

An Integrative in Silico Approach to Preclinical Drug Discovery. - Ann Arbor : ProQuest Dissertations & Theses, 2023 - 106 p.

Source: Dissertations Abstracts International, Volume: 84-12, Section: B.

Thesis (Ph.D.)--Indiana University, 2023.

The drug discovery process is a complex, laborious, error-prone process. Although many technological advancements have occurred over the last 100 years, it is still largely trial and error process with some of the biggest discoveries occurring through serendipity. Technology and informatics in approaches, more specifically, are changing this, enabling more rational approaches to drug discovery. Cheminformatics plays a central role in early preclinical drug discovery, from high throughput screening over vast compound libraries to drug repurposing with new indications. Technology advancements have occurred over the past decade, that when combined with innovations presented in this work, can be used to refine the drug discovery process in three areas:1. Synthesizability of small molecules and exploration of chemical space2. Medium-throughput screening with hydrogen deuterium exchange3. Drug repurposing with network pharmacology and graph analyticsThe research performed in this work combines three projects and cheminformatics sub disciplines, all in effort to create innovations and drive efficiencies in the early preclinical drug discovery process. Chemical synthesizability work was performed with Eli Lilly to understand the chemical space accessible to its automated synthetic laboratory. Synthesizability is a core requirement for any small molecule drug lead, and therefore, improvements on techniques for exploring chemical space for small molecule leads are critical. Techniques in classic cheminformatics were expounded to present Eli Lilly with a set of enriched scaffolds for further investigation and workup as part of their drug discovery program.Medium-throughput screening techniques are employed during lead development to refine the set of possible drug candidates by applying more stringent testing on the small molecule properties and pharmacology. An innovative algorithmic approach was developed here, employing the use of hydrogen deuterium exchange mass spectrometry on proteins to map small molecule-binding regions between small molecules and protein targets. This technique has broad appeal in general medium-throughput testing performed in early-stage drug discovery. Finally, network pharmacology approaches to drug repurposing were developed based on the comorbidity status of Parkinson's Disease with Melanoma. FDA-approved drugs were rank-ordered, with the most enriched drugs surfaced for further examination. Such techniques have broad applicability to the drug repurposing process and draw upon and extend algorithms developed in David Wild's group over the past 15 years.

ISBN: 9798379764609Subjects--Topical Terms:

553671
Bioinformatics.
Subjects--Index Terms:

Drug discovery

An Integrative in Silico Approach to Preclinical Drug Discovery.
LDR:03762nmm a2200385 4500 001 2401081
005 20241015112517.5
006 m o d
007 cr#unu||||||||
008 251215s2023 ||||||||||||||||| ||eng d
020 $a 9798379764609
035 $a (MiAaPQ)AAI30528558
035 $a AAI30528558
035 $a 2401081
040 $a MiAaPQ $c MiAaPQ
100 1 $a Gessner, Christopher. $3 3771141
245 1 3 $a An Integrative in Silico Approach to Preclinical Drug Discovery.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2023
300 $a 106 p.
500 $a Source: Dissertations Abstracts International, Volume: 84-12, Section: B.
500 $a Advisor: Wild, David J. .
502 $a Thesis (Ph.D.)--Indiana University, 2023.
520 $a The drug discovery process is a complex, laborious, error-prone process. Although many technological advancements have occurred over the last 100 years, it is still largely trial and error process with some of the biggest discoveries occurring through serendipity. Technology and informatics in approaches, more specifically, are changing this, enabling more rational approaches to drug discovery. Cheminformatics plays a central role in early preclinical drug discovery, from high throughput screening over vast compound libraries to drug repurposing with new indications. Technology advancements have occurred over the past decade, that when combined with innovations presented in this work, can be used to refine the drug discovery process in three areas:1. Synthesizability of small molecules and exploration of chemical space2. Medium-throughput screening with hydrogen deuterium exchange3. Drug repurposing with network pharmacology and graph analyticsThe research performed in this work combines three projects and cheminformatics sub disciplines, all in effort to create innovations and drive efficiencies in the early preclinical drug discovery process. Chemical synthesizability work was performed with Eli Lilly to understand the chemical space accessible to its automated synthetic laboratory. Synthesizability is a core requirement for any small molecule drug lead, and therefore, improvements on techniques for exploring chemical space for small molecule leads are critical. Techniques in classic cheminformatics were expounded to present Eli Lilly with a set of enriched scaffolds for further investigation and workup as part of their drug discovery program.Medium-throughput screening techniques are employed during lead development to refine the set of possible drug candidates by applying more stringent testing on the small molecule properties and pharmacology. An innovative algorithmic approach was developed here, employing the use of hydrogen deuterium exchange mass spectrometry on proteins to map small molecule-binding regions between small molecules and protein targets. This technique has broad appeal in general medium-throughput testing performed in early-stage drug discovery. Finally, network pharmacology approaches to drug repurposing were developed based on the comorbidity status of Parkinson's Disease with Melanoma. FDA-approved drugs were rank-ordered, with the most enriched drugs surfaced for further examination. Such techniques have broad applicability to the drug repurposing process and draw upon and extend algorithms developed in David Wild's group over the past 15 years.
590 $a School code: 0093.
650 4 $a Bioinformatics. $3 553671
650 4 $a Pharmacology. $3 634543
653 $a Drug discovery
653 $a Cheminformatics
653 $a Hydrogen deuterium
653 $a Molecule properties
653 $a Parkinson's disease
690 $a 0715
690 $a 0419
710 2 $a Indiana University. $b Informatics. $3 1680747
773 0 $t Dissertations Abstracts International $g 84-12B.
790 $a 0093
791 $a Ph.D.
792 $a 2023
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30528558