Expanding chemical probe space: quality criteria for covalent and degrader probes
Within druggable target space, new small-molecule modalities, particularly covalent
inhibitors and targeted degraders, have expanded the repertoire of medicinal chemists …
inhibitors and targeted degraders, have expanded the repertoire of medicinal chemists …
How many kinases are druggable? A review of our current understanding
There are over 500 human kinases ranging from very well-studied to almost completely
ignored. Kinases are tractable and implicated in many diseases, making them ideal targets …
ignored. Kinases are tractable and implicated in many diseases, making them ideal targets …
Delineating cysteine-reactive compound modulation of cellular proteostasis processes
AR Julio, F Shikwana, C Truong, NR Burton… - Nature Chemical …, 2024 - nature.com
Covalent modulators and covalent degrader molecules have emerged as drug modalities
with tremendous therapeutic potential. Toward realizing this potential, mass spectrometry …
with tremendous therapeutic potential. Toward realizing this potential, mass spectrometry …
Biophysical and computational approaches to study ternary complexes: a 'cooperative relationship'to rationalize targeted protein degradation
Degraders have illustrated that compound‐induced proximity to E3 ubiquitin ligases can
prompt the ubiquitination and degradation of disease‐relevant proteins. Hence, this …
prompt the ubiquitination and degradation of disease‐relevant proteins. Hence, this …
Systematic literature review reveals suboptimal use of chemical probes in cell-based biomedical research
Chemical probes have reached a prominent role in biomedical research, but their impact is
governed by experimental design. To gain insight into the use of chemical probes, we …
governed by experimental design. To gain insight into the use of chemical probes, we …
Critical assessment of LC3/GABARAP ligands used for degrader development and ligandability of LC3/GABARAP binding pockets
Recent successes in develo** small molecule degraders that act through the ubiquitin
system have spurred efforts to extend this technology to other mechanisms, including the …
system have spurred efforts to extend this technology to other mechanisms, including the …
Small molecules targeting DNA polymerase theta (POLθ) as promising synthetic lethal agents for precision cancer therapy
Synthetic lethality (SL) is an innovative strategy in targeted anticancer therapy that exploits
tumor genetic vulnerabilities. This topic has come to the forefront in recent years, as …
tumor genetic vulnerabilities. This topic has come to the forefront in recent years, as …
[HTML][HTML] A machine learning and live-cell imaging tool kit uncovers small molecules induced phospholipidosis
Summary Drug-induced phospholipidosis (DIPL), characterized by excessive accumulation
of phospholipids in lysosomes, can lead to clinical adverse effects. It may also alter …
of phospholipids in lysosomes, can lead to clinical adverse effects. It may also alter …
Which small molecule? selecting chemical probes for use in cancer research and target validation
Small-molecule chemical “probes” complement the use of molecular biology techniques to
explore, validate, and generate hypotheses on the function of proteins in diseases such as …
explore, validate, and generate hypotheses on the function of proteins in diseases such as …
canSAR 2024—an update to the public drug discovery knowledgebase
Abstract canSAR (https://cansar. ai) continues to serve as the largest publicly available
platform for cancer-focused drug discovery and translational research. It integrates …
platform for cancer-focused drug discovery and translational research. It integrates …