Fragment Screening - Drug Discovery Digest

Covalent Fragment Screening and Optimization Identifies the Chloroacetohydrazide Scaffold as Inhibitors for Ubiquitin C-terminal Hydrolase L1

Covalent Modifiers

MARCH 19, 2024

Herein, we describe a covalent fragment screen that identified the chloroacetohydrazide scaffold as a covalent UCHL1 inhibitor. Subsequent optimization provided an improved fragment with single-digit micromolar potency against UCHL1 and selectivity over the closely related UCHL3.

Fragment Screening

Fragment Screening Disease Treatment

APEIRON Biologics AG and Domainex Ltd announce the expansion of their partnership to progress targeted cancer immune therapy drug discovery

Drug Discovery Today

NOVEMBER 11, 2020

Integrated lead optimisation to advance APEIRON’s Cbl-b inhibitor development programme APN431; Inhibitors discovered at Domainex via virtual and fragment screening

Fragment Screening

Fragment Screening Therapies Drugs

Clustering Fragment Screening Hits With a Self-Organizing Map

Practical Cheminformatics

MARCH 28, 2022

Clustering Fragment Screening Hits With a Self-Organizing Map (SOM) In a paper, " Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking ", published last year by scientists from UCSF and the Diamond Light Source, the authors reported more than 200 structures of fragments bound (..)

Fragment Screening

Fragment Screening Screening Hits

Target-directed cancer: protein-ligand interactions

Drug Target Review

NOVEMBER 1, 2023

In terms of compound libraries, we have a high-throughput screening library of about 200,000 ligands. For fragment screening, which are much smaller compounds, we have a library of about 3000 fragments. We can screen with many different formats and modalities.

Fragment Screening

Fragment Screening Biochemical Assays Small Molecule Biophysical Assays

Silly Things Large Language Models Do With Molecules

Practical Cheminformatics

OCTOBER 8, 2024

Testing Claude’s Molecule Generation Ability To test the molecule generation ability of Claude, a general-purpose LLM from Anthropic, I prompted it to generate analogs for hits from fragment screens. These fragment hits are small molecules with between 11 and 21 heavy atoms.

Fragment Screening

Fragment Screening Packaging Organic Chemistry Small Molecule

Practical Cheminformatics - The Directory

Practical Cheminformatics

AUGUST 21, 2021

Adding Chemical Structures to a Recent COVID-19 Drug Repurposing Dataset Filtering Chemical Libraries Data Visualization / Plotting A Collection of Things I Frequently Forget How To Do With Seaborn Scatterplots Interactive Plots with Chemical Structures Visualizing Chemical Space Plotting Distributions Molecular Modeling Exploring the SARS-CoV-2 Main (..)

Fragment Screening

Fragment Screening Science Drugs

Structural Biology

Sygnature Discovery

SEPTEMBER 12, 2024

Cryo-EM Expert microscopists in house and access to high end microscopes for screening and high resolution data collection (Glacios, Tecnai, Titan Krios). Fragment Based Drug Discovery Crystallographic fragment screening using a high solubility curated fragment library devoid of soluble aggregates.

Fragment Screening

Fragment Screening RNA Protein Production DNA

COVID-19 stuff

Molecular Design

MAY 26, 2020

A crystallographic fragment screen has been run against SARS-CoV-2 and a number of electrophilic fragments were screened using mass spectroscopy. These two screens serve as a launch pad for the COVID Moonshot which looks interesting (although I’d suggest easing off a bit on the propaganda).

Fragment Screening

Fragment Screening Drugs

Tom Lehrer's guide to design of SARS-CoV-3 main protease inhibitors for treatment of COVID-32

Molecular Design

JANUARY 12, 2021

In the fourth of his rules for air fighting , ‘Sailor’ Malan (readers may also be interested in his insights into fragment screening library design ) asserts that “height gives you the initiative” which can be adapted for drug design as “affinity gives you the initiative”.

Fragment Screening

Fragment Screening Treatment Nurses Doctors

Reinventing the small molecule toolbox: from proteins to RNA

Dark Matter Blog

APRIL 4, 2023

We sampled several screening platforms in the course of our efforts, including fragment screening using ligand-observed nuclear magnetic resonance (NMR), DNA-encoded libraries (DEL), and SEC-MS. Each of these platforms is thoroughly vetted in protein world, but using them on RNA can yield surprising results.

Small Molecule

Small Molecule RNA Fragment Screening DNA

SARS-CoV-2 main protease. Crowdsourcing, peptidomimetics and fragments

Molecular Design

JULY 18, 2020

It’s also worth mentioning that fragment screens have been run against SARS-CoV-2 Nsp3 macrodomain at UCSF and Diamond since there are no known inhibitors for this target.

Biochemical Assays

Biochemical Assays Fragment Screening Pharmacokinetics Drugs

Biophysics

Sygnature Discovery

JUNE 17, 2024

Small Molecule Binding Assays · Fragment Screening · HTS Hit Validation · Virtual Screen Hit Confirmation · DEL Screening Hit Validation · Affinity/Kinetic Determination (lead identification/lead optimisation) 2. Nucleic Acid Targets: Focusing on specific interactions and functions.

Biophysical Assays

Biophysical Assays Screening Hits Assay Development Fragment Screening

Sygnature Discovery acquires Peak Proteins

Sygnature Discovery

APRIL 26, 2022

Their world-class expertise in protein crystallography will enhance our fragment screening and analysis activities, as well as our structure-based drug design work.” Mark Abbott, CEO of Peak Proteins, commented: “We have always valued Sygnature Discovery’s support and are now really pleased to be joining them.

Fragment Screening

Fragment Screening Protein Production Protein Expression Production

Biophysical Technologies

Sygnature Discovery

JUNE 17, 2024

Our in-house team of NMR experts specialises in ligand binding experiments using proton or fluorine NMR, particularly effective for small molecule-biomolecule binding assays and fragment screening, where it excels in detecting mM affinity binders.

Small Molecule

Small Molecule Fragment Screening DNA Science

SARS-CoV-2 Protease Inhibitors: An Attractive Approach for Treating COVID-19

PerkinElmer

JUNE 3, 2022

The second virtual screen focused on optimization of a hit from a previous crystallographic fragment screen. Fragment-to-lead optimization was guided by searches in a library of millions of compounds combined with docking screens to select the best candidate.

Fragment Screening

Fragment Screening Clinical Trials Vaccine Pharmacokinetics

Why fragments?

Molecular Design

AUGUST 2, 2020

Paramin panorama Crystallographic fragment screens have been run recently against the main protease (at Diamond ) and the Nsp3 macrodomain (at UCSF and Diamond ) of SARS-Cov-2 and I thought that it might be of interest to take a closer look at why we screen fragments.

Fragment Screening

Fragment Screening Computational Chemistry Engineering Drugs

Open-source Electrophilic Fragment Screening Platform to Identify Chemical Starting Points for UCHL1 Covalent Inhibitors

Covalent Modifiers

DECEMBER 3, 2024

Screening covalent fragments against purified protein targets reduces the demands on the mass spectrometer with respect to absolute throughput, detection limit, and dynamic range.

Fragment Screening

Fragment Screening Compound Screening Small Molecule Drugs

Drug Discovery Digest

Covalent Fragment Screening and Optimization Identifies the Chloroacetohydrazide Scaffold as Inhibitors for Ubiquitin C-terminal Hydrolase L1

APEIRON Biologics AG and Domainex Ltd announce the expansion of their partnership to progress targeted cancer immune therapy drug discovery

Trending Sources

Clustering Fragment Screening Hits With a Self-Organizing Map

Target-directed cancer: protein-ligand interactions

Silly Things Large Language Models Do With Molecules

Practical Cheminformatics - The Directory

Structural Biology

COVID-19 stuff

Tom Lehrer's guide to design of SARS-CoV-3 main protease inhibitors for treatment of COVID-32

Reinventing the small molecule toolbox: from proteins to RNA

SARS-CoV-2 main protease. Crowdsourcing, peptidomimetics and fragments

Biophysics

Sygnature Discovery acquires Peak Proteins

Biophysical Technologies

SARS-CoV-2 Protease Inhibitors: An Attractive Approach for Treating COVID-19

Why fragments?

Open-source Electrophilic Fragment Screening Platform to Identify Chemical Starting Points for UCHL1 Covalent Inhibitors

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