N. S. Gray

Rewiring Cancer Drivers to Activate Apoptosis

This paper introduces TCIPs, molecules that activate cell death by rewiring cancer drivers, showing efficacy against DLBCL and potential for broader therapeutic applications.

Template-assisted covalent modification of DCAF16 underlies activity of BRD4 molecular glue degraders

This paper describes a new mechanism for molecular glue degraders called template-assisted covalent modification, showing how BRD4 degraders recruit CUL4DCAF16 to degrade BRD4.

Development and utility of a PAK1-selective degrader

This study develops a PAK1-selective degrader, BJG-05-039, which shows enhanced anti-proliferative effects compared to the parent inhibitor NVS-PAK1-1 in PAK1-dependent cell lines.

The kinase activity of the cancer stem cell marker DCLK1 drives gastric cancer progression by reprogramming the stromal tumor landscape

This study identifies DCLK1 kinase activity as a driver of gastric cancer progression by reprogramming the tumor stroma and promoting invasiveness and metastasis.

Development of PRPK Directed Phthalimides

This paper develops PRPK-directed phthalimides based on pomalidomide, identifies a potent and selective PRPK binder, and highlights distinct binding mechanisms compared to cereblon.

The CDK8 inhibitor DCA promotes a tolerogenic chemical immunophenotype in CD4+ T cells via a novel CDK8-GATA3-FOXP3 pathway

The paper identifies DCA as a CDK8 inhibitor that induces a tolerogenic immunophenotype in CD4+ T cells through a novel CDK8-GATA3-FOXP3 pathway, promoting Treg and Th2 differentiation while inhibiting Th1 and Th17.

Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption

The paper shows that YKL-05-099, which inhibits SIKs and CSF1R, increases bone formation without increasing bone resorption in mice.

Targeting EGFR in glioblastoma with a novel brain-penetrant small molecule EGFR-TKI

This paper introduces a novel EGFR-TKI, CM93, which shows improved brain penetration and efficacy against EGFR-mutated glioblastoma in vitro and in vivo.

Catalytic domain plasticity of MKK7 reveals structural mechanisms of allosteric activation and new targeting opportunities

This study presents MKK7 crystal structures and identifies new allosteric targets, revealing structural mechanisms of activation and potential drug candidates.

Sulfopin, a selective covalent inhibitor of Pin1, blocks Myc-driven tumor initiation and growth in vivo

Sulfopin, a selective Pin1 inhibitor, reduces tumor initiation and growth in neuroblastoma models by targeting c-Myc pathways.

Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules

This paper introduces dTAGV-1, a VHL-recruiting dTAG molecule that rapidly degrades FKBP12F36V-tagged proteins, overcoming limitations of CRBN-recruiting dTAGs and enabling combination degrader studies in cells and mice.

CM93, a novel covalent small molecule inhibitor targeting lung cancer with mutant EGFR

The paper develops CM93, a novel EGFR inhibitor with improved targeting and brain penetration, showing better efficacy and safety in mouse models of EGFR-mutant NSCLC and brain metastases.

The Kinase Chemogenomic Set (KCGS): An open science resource for kinase vulnerability identification

The paper introduces the Kinase Chemogenomic Set (KCGS), a curated collection of 187 selective kinase inhibitors covering 215 human kinases, for use in cell-based screens.

Discovery of an AKT Degrader with Prolonged Inhibition ofDownstream Signaling

This study develops INY-03-041, a pan-AKT degrader that shows prolonged inhibition of AKT and downstream signaling effects compared to traditional inhibitors.

STRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation

The paper shows STRIPAK directs PP2A to dephosphorylate MAP4K4, promoting oncogenic transformation via YAP1 activation.

Targeting the PI5P4K lipid kinase family in cancer using novel covalent inhibitors

This study identifies THZ-P1-2, a covalent pan-PI5P4K inhibitor, showing efficacy in AML/ALL cell lines and autophagy disruption, supporting PI5P4Ks as therapeutic targets in cancer.

Defining and targeting adaptations to oncogenic KRASG12C inhibition using quantitative temporal proteomics

This study uses quantitative temporal proteomics to analyze KRASG12C inhibitor responses in cancer models, identifying effective drug combinations to overcome resistance.

Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15

The paper reveals how E7820 promotes RBM39 degradation via DCAF15 by binding to a non-conserved pocket on DCAF15, bypassing the need for high-affinity ligands.

Combined inhibition of mTOR and PIKKs exploits replicative and checkpoint vulnerabilities to induce death of PI3K-activated triple-negative breast cancer cells

The paper shows that combining mTOR and PIKK inhibitors kills triple-negative breast cancer cells by exploiting replication and checkpoint vulnerabilities.

CDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation

This study shows CDK12 inhibition causes premature cleavage and polyadenylation in long DNA damage response genes, linked to their length and polyadenylation site distribution.

How small-molecule inhibitors of dengue-virus infection interfere with viral membrane fusion

The paper studies how small-molecule inhibitors block dengue virus membrane fusion by targeting the envelope protein's conformational change, showing that ~15 bound molecules per particle prevent fusion.