B. F. Cravatt

Redirecting the pioneering function of FOXA1 with covalent small molecules

This study identifies covalent small molecules that bind FOXA1, altering its chromatin remodeling activity in prostate cancer cells.

Expanding the ligandable proteome by paralog hopping with covalent probes

The paper uses covalent probes and paralog hopping to identify ligandable pockets in proteins lacking cysteines, demonstrating a method to expand the ligandable proteome.

Covalent Targeting of Splicing in T Cells.

This study develops chemical probes to target splicing factors in T cells, showing state-dependent loss of ITK via SF3B1 and demonstrating covalent ligandability of splicing regulators.

Human STING oligomer function is governed by palmitoylation of an evolutionarily conserved cysteine

This paper identifies palmitoylation at C64 as critical for preventing unproductive STING oligomerization and shows a peptide inhibitor targeting the oligomerization interface.

Stimulatory effect of monoacylglycerol lipase inhibitor MJN110 on locomotion and step kinematics demonstrated by high-precision 3D motion capture in mice

This study shows that inhibiting monoacylglycerol lipase (MJN110) enhances locomotion and step kinematics in mice, while inhibiting fatty acid amide hydrolase (PF3845) suppresses it, revealing distinct effects of endocannabinoid pathway manipulations on motor behavior.

Glutathione supports lipid abundance in vivo

This study shows that glutathione (GSH) is essential for lipid abundance in adult tissues, particularly in the liver, by repressing NRF2.

The metabolite alpha-ketobutyrate increases health and life spans by activating AMPK

This paper shows that alpha-ketobutyrate extends lifespan and healthspan in C. elegans and mice by activating AMPK through MACF1/VAB-10.

TMEM164 is an acyltransferase that forms ferroptotic polyunsaturated ether phospholipids

The paper identifies TMEM164 as an acyltransferase that produces PUFA ether phospholipids, essential for ferroptosis, and shows its absence reduces these lipids and protects cells from ferroptosis.

Collateral lethality between HDAC1 and HDAC2 exploits cancer-specific NuRD complex vulnerabilities

The paper identifies collateral synthetic lethality between HDAC1 and HDAC2 in cancer cells and shows that targeting HDAC2 can suppress tumor growth by disrupting the NuRD complex.

Selective inhibitors of JAK1 targeting a subtype-restricted allosteric cysteine

This study identifies an allosteric cysteine in JAK1 and TYK2, develops inhibitors targeting it, and shows high subtype selectivity with minimal off-target effects.

A competitive activity-based protein profiling platform yields cell wall synthesis inhibitors active against replicating and non-replicating Mycobacterium tuberculosis

This study uses ABPP to identify cell wall synthesis inhibitors targeting Mycobacterium tuberculosis, showing that active compounds inhibit serine hydrolases involved in cell wall and lipid metabolism.

Targeting Glioblastoma Signaling and Metabolism with A Re-Purposed Brain-Penetrant Drug

This study identifies fluoxetine as a potential therapy for glioblastoma by inhibiting SMPD1 and enhancing temozolomide efficacy, with real-world evidence suggesting improved survival.

Chemical inhibition of ENL/AF9 YEATS domains in acute leukemia

This study identifies a potent inhibitor of the ENL/AF9 YEATS domain and demonstrates its selective suppression of ENL-dependent leukemia genes.

ABHD17 enzymes regulate dynamic plasma membrane palmitoylation and N-Ras-dependent cancer growth

This study identifies ABD957, a selective ABHD17 inhibitor, which disrupts N-Ras depalmitoylation and inhibits NRAS-mutant AML growth, suggesting potential as a targeted therapy.

Integrative x-ray structure and molecular modeling for the rationalization of procaspase-8 inhibitor potency and selectivity

The paper uses X-ray crystallography and molecular modeling to study how a small-molecule inhibitor binds to and inhibits procaspase-8, revealing structural changes and key interactions.

Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16

The paper identifies DCAF16 as a component that enables nuclear protein degradation via electrophilic PROTACs.