A Photoaffinity Labeling-Based Chemoproteomics Strategy for Unbiased Target Deconvolution of Small Molecule Drug Candidates

Targeted Protein Degradation (TPD) is an emerging new modality of drug discovery that offers unprecedented therapeutic benefits over traditional protein inhibition. Most importantly, TPD unlocks the untapped pool of the proteome that to date has been considered undruggable. Captor Therapeutics (Captor) is the fourth global, and first European, company that develops small molecule drug candidates based on the principles of targeted protein degradation. Captor is located in Basel, Switzerland and Wroclaw, Poland and exploits the best opportunities of the two sites – experience and non-dilutive European grants, and talent pool, respectively. Through over $38 M of funding, Captor has been active in three areas of TPD: molecular glues, bi-specific degraders and direct degraders, ObteronsTM.

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Peptide-Level Interactions between Proteins and Small-Molecule Drug Candidates by Two Hydrogen−Deuterium Exchange MS-Based Methods: The Example of Apolipoprotein E3

Analytical Chemistry ◽

10.1021/acs.analchem.7b01121 ◽

2017 ◽

Vol 89 (20) ◽

pp. 10687-10695 ◽

Cited By ~ 12

Author(s):

Hanliu Wang ◽

Don L. Rempel ◽

Daryl Giblin ◽

Carl Frieden ◽

Michael L. Gross

Keyword(s):

Small Molecule ◽

Deuterium Exchange ◽

Hydrogen Deuterium Exchange ◽

Drug Candidates ◽

Small Molecule Drug ◽

Peptide Level ◽

Hydrogen Deuterium

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How polypharmacologic is each chemogenomics library?

Future Drug Discovery ◽

10.4155/fdd-2019-0032 ◽

2020 ◽

Vol 2 (1) ◽

pp. FDD26 ◽

Cited By ~ 1

Author(s):

Eric Ni ◽

Eehjoe Kwon ◽

Lauren M. Young ◽

Klara Felsovalyi ◽

Jennifer Fuller ◽

...

Keyword(s):

Drug Discovery ◽

Small Molecule ◽

High Throughput ◽

Boltzmann Distribution ◽

Target Specificity ◽

Small Molecule Drug ◽

Target Deconvolution ◽

Phenotypic Screen ◽

Promising Avenue

Aim: High-throughput phenotypic screens have emerged as a promising avenue for small-molecule drug discovery. The challenge faced in high-throughput phenotypic screens is target deconvolution once a small molecule hit is identified. Chemogenomics libraries have emerged as an important tool for meeting this challenge. Here, we investigate their target-specificity by deriving a ‘polypharmacology index’ for broad chemogenomics screening libraries. Methods: All known targets of all the compounds in each library were plotted as a histogram and fitted to a Boltzmann distribution, whose linearized slope is indicative of the overall polypharmacology of the library. Results & conclusion: Comparison of libraries clearly distinguished the most target-specific library, which might be assumed to be more useful for target deconvolution in a phenotypic screen.

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Small Molecule Drug Candidates for Managing the Clinical Symptoms of COVID-19: a Narrative Review

Biomolecules & Therapeutics ◽

10.4062/biomolther.2021.134 ◽

2021 ◽

Author(s):

Chawon Yun ◽

Hyun Jae Lee ◽

Choong Jae Lee

Keyword(s):

Small Molecule ◽

Clinical Symptoms ◽

Narrative Review ◽

Drug Candidates ◽

Small Molecule Drug

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Cu(i)-mediated 18F-trifluoromethylation of arenes: Rapid synthesis of 18F-labeled trifluoromethyl arenes

Chemical Communications ◽

10.1039/c4cc01641f ◽

2014 ◽

Vol 50 (45) ◽

pp. 6056-6059 ◽

Cited By ~ 46

Author(s):

T. Rühl ◽

W. Rafique ◽

V. T. Lien ◽

P. J. Riss

Keyword(s):

Positron Emission Tomography ◽

Small Molecule ◽

Emission Tomography ◽

Rapid Synthesis ◽

Fluoride Ions ◽

Drug Candidates ◽

Small Molecule Drug ◽

Positron Emission

An efficient, CuI-mediated method for the radiosynthesis of [18F]trifluoromethyl arenes, abundant motifs in small molecule drug candidates and potential radiotracers for positron emission tomography starting from [18F]fluoride ions is described.

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