A. Dong

CACHE Challenge #1: targeting the WDR domain of LRRK2, a Parkinson's Disease associated protein.

The paper evaluates computational hit-finding methods for targeting the WDR domain of LRRK2, a Parkinson's disease protein, finding that diverse strategies yielded weakly potent compounds.

A resource to enable chemical biology and drug discovery of WDR Proteins

The paper develops a resource for discovering ligands for WDR proteins using experimental and computational methods, leading to the identification of drug-like ligands for 9 out of 20 targets.

The Implant-Induced Foreign Body Response is Limited by CD13-Dependent Regulation of Ubiquitination of Fusogenic Proteins

This study shows CD13 regulates macrophage fusion by controlling ubiquitination of fusogenic proteins, limiting foreign body response fibrosis and suggesting CD13 as a therapeutic target.

Chemical Tools for the Gid4 Subunit of the Human E3 Ligase C-terminal to LisH (CTLH) Degradation Complex

The paper develops chemical tools and probes for the Gid4 subunit of the human CTLH E3 ligase complex, achieving sub-100 nM binding affinity for further study.

Probing the mechanism of Cbl-b inhibition by a small-molecule inhibitor

The paper investigates how a small-molecule inhibitor binds to and inactivates Cbl-b, revealing a structural mechanism that locks the protein in an inactive conformation.

Pharmacological characterization of the endocannabinoid sensor GRABeCB2.0

This study characterizes the pharmacological response of the GRABeCB2.0 sensor to endocannabinoids and cannabinoids, finding that its EC50 values for 2-AG and SR1 match CB1R potencies, while others show lower EC50s, and CBD acts as a negative allosteric modulator.

Caltubin regulates microtubule stability via Ca2+-dependent mechanisms favouring neurite regrowth

This study shows caltubin enhances neurite regrowth in neurons by stabilizing microtubules through Ca2+-dependent mechanisms.

ABHD6 selectively controls metabotropic-dependent increases in 2-AG production

The paper shows ABHD6 selectively regulates metabotropic-dependent 2-AG production via DAGL and calcium, unlike ionotropic-dependent increases.

Discovery of small molecule antagonists of human Retinoblastoma Binding Protein 4 (RBBP4)

This study identifies small molecule antagonists of RBBP4's top pocket, competes with protein and histone interactions, and reports the first crystal structure of RBBP4 with a small molecule.

Structural and functional characterization of ubiquitin variant inhibitors for the JAMM-family deubiquitinases STAMBP and STAMBPL1

This paper develops Ub variant inhibitors for JAMM-family DUBs STAMBP and STAMBPL1, showing high affinity and selectivity, with structural insights and improved potency over existing inhibitors.

Structure Activity Relationship of USP5 Allosteric Inhibitors

This paper develops a chemical series of USP5 allosteric inhibitors, identifies a selective compound with structural and functional characterization.

Pharmacological targeting of a PWWP domain demonstrates cooperative control of NSD2 localization

The paper develops a chemical probe, UNC6934, that targets the PWWP1 domain of NSD2, revealing cooperative control of NSD2 localization through chromatin reader domains.

Impact of the radiated brain microenvironment on a panel of human patient-derived xenografts.

This study evaluates how the radiated brain microenvironment affects the growth of nine human glioblastoma cell lines, finding that some tumors grow faster while others grow slower in this environment.

Identification and Characterization of the First Fragment Hits for SETDB1 Tudor Domain

The paper identifies small molecule fragments that bind to the tudor domain of SETDB1 and describes their binding modes and biophysical properties.

A Chemical Probe of CARM1 Alters Epigenetic Plasticity against Breast Cancer Cell Invasion

This study identifies SKI-73 as a CARM1 chemical probe that reduces breast cancer cell invasion by altering epigenetic plasticity, distinct from CARM1 knockout effects.