Discovery Methodology of Novel Conotoxins from Conus Species

Cone snail venoms provide an ideal resource for neuropharmacological tools and drug candidates discovery, which have become a research hotspot in neuroscience and new drug development. More than 1,000,000 natural peptides are produced by cone snails, but less than 0.1% of the estimated conotoxins has been characterized to date. Hence, the discovery of novel conotoxins from the huge conotoxin resources with high-throughput and sensitive methods becomes a crucial key for the conotoxin-based drug development. In this review, we introduce the discovery methodology of new conotoxins from various Conus species. It focuses on obtaining full N- to C-terminal sequences, regardless of disulfide bond connectivity through crude venom purification, conotoxin precusor gene cloning, venom duct transcriptomics, venom proteomics and multi-omic methods. The protocols, advantages, disadvantages, and developments of different approaches during the last decade are summarized and the promising prospects are discussed as well.

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New drug development by United States pharmaceutical firms: With analyses of trends in the acquisition and origin of drug candidates, 1963-1979*

Clinical Pharmacology & Therapeutics ◽

10.1038/clpt.1982.181 ◽

1982 ◽

Vol 32 (4) ◽

pp. 407-417 ◽

Cited By ~ 14

Author(s):

William M Wardell ◽

Maureen S May ◽

A Gene Trimble

Keyword(s):

United States ◽

Drug Development ◽

Drug Candidates ◽

Pharmaceutical Firms ◽

New Drug ◽

New Drug Development

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Integrating gene expression and clinical data to identify drug repurposing candidates for hyperlipidemia and hypertension

Nature Communications ◽

10.1038/s41467-021-27751-1 ◽

2022 ◽

Vol 13 (1) ◽

Author(s):

Patrick Wu ◽

QiPing Feng ◽

Vern Eric Kerchberger ◽

Scott D. Nelson ◽

Qingxia Chen ◽

...

Keyword(s):

Gene Expression ◽

Drug Development ◽

Clinical Data ◽

High Throughput ◽

Research Program ◽

Human Gene ◽

Drug Repurposing ◽

Therapeutic Effects ◽

New Drug Development ◽

Approved Drugs

AbstractDiscovering novel uses for existing drugs, through drug repurposing, can reduce the time, costs, and risk of failure associated with new drug development. However, prioritizing drug repurposing candidates for downstream studies remains challenging. Here, we present a high-throughput approach to identify and validate drug repurposing candidates. This approach integrates human gene expression, drug perturbation, and clinical data from publicly available resources. We apply this approach to find drug repurposing candidates for two diseases, hyperlipidemia and hypertension. We screen >21,000 compounds and replicate ten approved drugs. We also identify 25 (seven for hyperlipidemia, eighteen for hypertension) drugs approved for other indications with therapeutic effects on clinically relevant biomarkers. For five of these drugs, the therapeutic effects are replicated in the All of Us Research Program database. We anticipate our approach will enable researchers to integrate multiple publicly available datasets to identify high priority drug repurposing opportunities for human diseases.

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A Basic Study on Collaborative Plan of Translational Service Research for Accelerating New Drug Development

Journal of Korea Service Management Society ◽

10.15706/jksms.2014.15.1.014 ◽

2014 ◽

Vol 15 (1) ◽

pp. 283-306

Author(s):

Kim, Chang Won ◽

Lee Cheol-Gyu ◽

Youn Sung Kim ◽

WangJin Yoo

Keyword(s):

Drug Development ◽

Service Research ◽

Basic Study ◽

New Drug ◽

New Drug Development

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Novel GABAA Agonist Entities: Pharmacological Investigation and Molecular Modeling Study of Thiazolo- and Thiadiazolo-[3,2-a][1,3] diazepine Analogs

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521999201230195733 ◽

2020 ◽

Vol 21 ◽

Author(s):

Hussein I. El-Subbagh

Keyword(s):

Molecular Modeling ◽

Drug Development ◽

Biological Evaluation ◽

Neuromuscular Blocking ◽

Present Review ◽

Pharmacological Investigation ◽

Important Class ◽

Pharmacological Activities ◽

Short Acting ◽

New Drug Development

Abstract:: Thiazolo- and thiadiazolo-[3,2-a][1,3]diazepines and their patented derivatives, tested with diverse CNS pharmacological activities, constitute an important class of compounds for new drug development. Therefore, research efforts were continued to design, synthesize, and evaluate compounds for their ultra-short, short-acting hypnotic, anticonvulsant, and neuromuscular blocking activities. The present review provides a summary of the work accomplished by these heterocycles and their biological evaluation.

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High-throughput behavioral screen in C. elegans reveals Parkinson’s disease drug candidates

Communications Biology ◽

10.1038/s42003-021-01731-z ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Salman Sohrabi ◽

Danielle E. Mor ◽

Rachel Kaletsky ◽

William Keyes ◽

Coleen T. Murphy

Keyword(s):

Neural Network ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

High Throughput ◽

Potential Candidate ◽

Automated Scoring ◽

C Elegans ◽

Drug Candidates ◽

Branched Chain ◽

Approved Drugs

AbstractWe recently linked branched-chain amino acid transferase 1 (BCAT1) dysfunction with the movement disorder Parkinson’s disease (PD), and found that RNAi-mediated knockdown of neuronal bcat-1 in C. elegans causes abnormal spasm-like ‘curling’ behavior with age. Here we report the development of a machine learning-based workflow and its application to the discovery of potentially new therapeutics for PD. In addition to simplifying quantification and maintaining a low data overhead, our simple segment-train-quantify platform enables fully automated scoring of image stills upon training of a convolutional neural network. We have trained a highly reliable neural network for the detection and classification of worm postures in order to carry out high-throughput curling analysis without the need for user intervention or post-inspection. In a proof-of-concept screen of 50 FDA-approved drugs, enasidenib, ethosuximide, metformin, and nitisinone were identified as candidates for potential late-in-life intervention in PD. These findings point to the utility of our high-throughput platform for automated scoring of worm postures and in particular, the discovery of potential candidate treatments for PD.

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