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Chemogenomics Knowledgebase and Systems Pharmacology for Hallucinogen Target Identification -Salvinorin A as a Case Study

Xu, Xiaomeng (2015) Chemogenomics Knowledgebase and Systems Pharmacology for Hallucinogen Target Identification -Salvinorin A as a Case Study. Master's Thesis, University of Pittsburgh. (Unpublished)

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Drug abuse is a serious problem worldwide. Recently, hallucinogens have been reported as a potential therapy for substance abuse. However, the use of hallucinogens as a drug abuse treatment itself has potential risks. The true mechanisms of hallucinogens are not clear. Thus it is necessary to investigate the mechanism of hallucinogens to make sure they are safe to develop as medicine. So far, no scientific database is available for the mechanism research of hallucinogens.
We constructed a hallucinogen-specific chemogenomics database by collecting chemicals, protein targets and pathways closely related to hallucinogens. This information, together with our established computational chemogenomics tools, such as TargetHunter and HTDocking, provided a one-step solution for the mechanism study of hallucinogens.
We chose salvinorin A as an example to demonstrate the usability of our platform. Salvinorin A is a potent hallucinogen extracted from the plant Salvia divinorum. It was the first reported non-nitrogenous kappa opioid receptor agonist. Recently, researchers found that oral administration of salvinorin A can affect drug choice in a monkey model, which suggested a potential use of salvinorin A as an abuse-deterrent formulation. However, some complex effects of salvinorin A were reported, including depersonalization or laughing hysterically. Our aim is to identify the potential targets of salvinorin A to further explore the mechanisms of its complex effects.
With the help of HTDocking program, we predicted four novel targets for salvinorin A, including muscarinic acetylcholine receptor 2, cannabinoid receptor 1, cannabinoid receptor 2 and dopamine receptor 2. We looked into the interactions between salvinorin A and the predicted targets, and compared their binding modes with the known ligands of these proteins. The similar binding modes, interactions and high docking scores indicate that salvinorin A may interact with these four predicted targets. In the future, we will design experiments or find collaborators to validate our predictions. At the same time, we will continuously enrich our hallucinogen-specific chemogenomics database by adding newest data and building more 3D homology models.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Xu, Xiaomengxix37@pitt.eduXIX37
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairKirisci, Leventlevent@pitt.eduLEVENT
Committee MemberXie, Xiang-Qunxix15@pitt.eduXIX15
Committee MemberWang, Lirongliw30@pitt.eduLIW30
Date: 6 April 2015
Date Type: Publication
Defense Date: 24 March 2015
Approval Date: 6 April 2015
Submission Date: 1 April 2015
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 60
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: hallucinogen, salvinorin A, drug abuse, chemogenomics database, cloud computation, target identification, systems pharmacology, homology modeling, natural product, drug discovery.
Date Deposited: 06 Apr 2015 13:16
Last Modified: 15 Nov 2016 14:26


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