Abstract 4953: Identification of direct target engagement biomarkers for kinase drug discovery using quantitative mass spectrometry: PDK1 case study

A viral development of statistical data processing, computing capabilities, chromatography-mass spectrometry, and omics technologies (technologies based on the achievements of genomics, transcriptomics, proteomics, metabolomics) in recent decades has not led to formation of a unified protocol for untargeted profiling. Systematic errors reduce the reproducibility and reliability of the obtained results, and at the same time hinder consolidation and analysis of data gained in large-scale multi-day experiments. We propose an algorithm for conducting omics profiling to identify potential markers in the samples of complex composition and present the case study of urine samples obtained from different clinical groups of patients. Profiling was carried out by the method of liquid chromatography mass spectrometry. The markers were selected using methods of multivariate analysis including machine learning and feature selection. Testing of the approach was performed using an independent dataset by clustering and projection on principal components.

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Faculty Opinions recommendation of Identification of psoriatic arthritis mediators in synovial fluid by quantitative mass spectrometry.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726854649.793524424 ◽

2016 ◽

Author(s):

Dafna Gladman

Keyword(s):

Mass Spectrometry ◽

Psoriatic Arthritis ◽

Synovial Fluid ◽

Quantitative Mass Spectrometry

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Pure Biologics – From a Bootstrapped Boutique CRO to an Integrated Drug Discovery Public Company

Technology Transfer and Entrepreneurship ◽

10.2174/2213809907666200313114152 ◽

2020 ◽

Vol 7 (1) ◽

pp. 48-63

Author(s):

Sameer Deshmukh ◽

Przemysław Jurek ◽

Filip Jelen ◽

Sabina Tabaczar ◽

Tomasz Bakowski ◽

...

Keyword(s):

Drug Discovery ◽

Present Article ◽

Small And Medium Enterprises ◽

Public Funding ◽

Corporate Management ◽

Publicly Traded ◽

Biopharmaceutical Company ◽

Public Company ◽

Medium Enterprises

The present article is a case study of a Polish biopharmaceutical company, “Pure Biologics”. The company was founded in 2010 by a group of scientists and, over the last nine years, grew substantially from just a few individuals to nearly one hundred professionals. Initially, a privately-funded civil partnership, Pure Biologics, has been transformed into a publicly-traded company. Such a transformation has been possible not only because of the expertise and growing experience of corporate management, but also the specific economic environment and substantial public funding dedicated to innovative Small and Medium Enterprises (SMEs).

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High-Throughput Affinity Selection Mass Spectrometry Using SAMDI-MS to Identify Small-Molecule Binders of the Human Rhinovirus 3C Protease

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/24725552211023211 ◽

2021 ◽

pp. 247255522110232

Author(s):

Michael D. Scholle ◽

Doug McLaughlin ◽

Zachary A. Gurard-Levin

Keyword(s):

Mass Spectrometry ◽

Drug Discovery ◽

High Throughput ◽

High Throughput Screening ◽

Human Rhinovirus ◽

Binding Potential ◽

Affinity Selection ◽

Response Curves ◽

Desorption Ionization ◽

Self Assembled

Affinity selection mass spectrometry (ASMS) has emerged as a powerful high-throughput screening tool used in drug discovery to identify novel ligands against therapeutic targets. This report describes the first high-throughput screen using a novel self-assembled monolayer desorption ionization (SAMDI)–ASMS methodology to reveal ligands for the human rhinovirus 3C (HRV3C) protease. The approach combines self-assembled monolayers of alkanethiolates on gold with matrix-assisted laser desorption ionization time-of-flight (MALDI TOF) mass spectrometry (MS), a technique termed SAMDI-ASMS. The primary screen of more than 100,000 compounds in pools of 8 compounds per well was completed in less than 8 h, and informs on the binding potential and selectivity of each compound. Initial hits were confirmed in follow-up SAMDI-ASMS experiments in single-concentration and dose–response curves. The ligands identified by SAMDI-ASMS were further validated using differential scanning fluorimetry (DSF) and in functional protease assays against HRV3C and the related SARS-CoV-2 3CLpro enzyme. SAMDI-ASMS offers key benefits for drug discovery over traditional ASMS approaches, including the high-throughput workflow and readout, minimizing compound misbehavior by using smaller compound pools, and up to a 50-fold reduction in reagent consumption. The flexibility of this novel technology opens avenues for high-throughput ASMS assays of any target, thereby accelerating drug discovery for diverse diseases.

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