Patrick McCarren
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View article: Supplemental Figure 1 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 1 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
Characterization of MC38_sgStk11 mouse model
View article: Supplemental Table 6 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Table 6 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
10 patients with STK11-deficient solid tumors enrolled in NCT05887492 provided paired biopsies during Phase 1
View article: Supplemental Table 5 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Table 5 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
Peptides that had significantly changed acetylation in response to treatment with either TNG260, entinostat, or vorinostat in pan-acetyl proteomics experiment
View article: Supplemental Figure 9 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 9 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
TNG260 treatment does not affect proportion of intratumoral Treg cells
View article: Supplemental Table 1 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Table 1 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
Antibodies and dilutions for western blotting
View article: Supplemental Figure 5 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 5 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
TNG260 has the potential for greater therapeutic index than approved HDAC inhibitors
View article: Data from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Data from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
Patients with non–small cell lung cancer (NSCLC) with loss of the tumor suppressor gene STK11 are resistant to immune checkpoint therapies like anti–PD-1. In this study, we conducted an in vivo CRISPR screen that identified histone deacety…
View article: Supplemental Figure 3 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 3 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
TNG260 is selective against HDAC3-9, 11
View article: Supplemental Table 3 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Table 3 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
CRISPR score results for the comparison of MC38_sgSTK11 tumors in C57BL/6 mice treated with anti-PD-1 compared to MC38_sgSTK11 tumors in athymic nude mice
View article: Supplemental Table 4 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Table 4 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
CRISPR score results for the comparison of MC38_sgSTK11 tumors to MC38_sgNTC tumors in C57BL/6 mice treated with anti-PD1
View article: Supplemental Figure 2 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 2 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
In-vivo immune sensitizer screen in STK11-isogenic MC38 tumors
View article: Supplemental Figure 7 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 7 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
Transcriptomic landscape modulation by TNG260
View article: Supplemental Figure 6 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 6 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
TNG260 has a favorable toxicity profile against hematopoietic lineages in vitro
View article: Supplemental Figure 8 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 8 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
TNG260 increases antigen presentation in STK11-deficient cells
View article: Supplemental Table 2 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Table 2 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
Antibodies for flow cytometry
View article: Supplemental Figure 4 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 4 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
TNG260 creates a more active immune microenvironment
View article: TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i> -Mutant Tumors to Anti–PD-1 Immunotherapy
TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i> -Mutant Tumors to Anti–PD-1 Immunotherapy Open
Patients with non–small cell lung cancer (NSCLC) with loss of the tumor suppressor gene STK11 are resistant to immune checkpoint therapies like anti–PD-1. In this study, we conducted an in vivo CRISPR screen that identified histone deacety…
View article: Supplementary Figure S4 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers
Supplementary Figure S4 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers Open
LIG1 inactivation is lethal in BRCA1-mutant MDA-MB-436 cells, and is rescued by exogenous expression of wild-type BRCA1. A) Representative colony formation assay (treatment day 14) using DOX-inducible shRNA against LIG1, PLK1 (pan-lethal c…
View article: Supplementary Figure S5 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers
Supplementary Figure S5 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers Open
LIG1 inactivation is lethal in HRD+ BRCA1/2 wild-type HCC1806 cells. A) Representative colony formation assay (treatment day 11) using DOX-inducible shRNA against LIG1, PLK1 (pan-lethal control), or a control sequence in HCC1806 cells. B) …
View article: Supplementary Figure S2 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers
Supplementary Figure S2 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers Open
CRISPRi system does not reduce viability of BRCA mutant cells using an intron-targeting control guide RNA (sgITC). Representative image (A) and quantification (B) of colony formation assay (treatment day 14) in MDA-MB-436 (BRCA1 mutant) ce…
View article: Data from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers
Data from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers Open
Synthetic lethality approaches in BRCA1/2-mutated cancers have focused on PARP inhibitors, which are subject to high rates of innate or acquired resistance in patients. In this study, we used CRISPR/Cas9-based screening to identify DNA lig…
View article: Supplementary Figure S6 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers
Supplementary Figure S6 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers Open
Perturbation of LIG1 induces proportional PAR accumulation in BRCA1-mutated cells in immunofluorescence and in-cell western assay formats. A) In-cell Western blotting of PAR on treatment day 4 in MDA-MB-436 cells engineered to express a DO…
View article: Supplementary Data from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers
Supplementary Data from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers Open
Supplementary Materials
View article: Supplementary Figure S3 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers
Supplementary Figure S3 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers Open
Quantification of western blots for dTAG-mediated LIG1 degradation. MDA-MB-436 cells were engineered to express a CRISPR-resistant LIG1 cDNA fused to either the FKBP12mut (dTAG) degron (degradable) (A) or the FKBP12wt degron (non-degradabl…
View article: Supplementary Figure S7 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers
Supplementary Figure S7 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers Open
Withdrawal of Doxycycline leads to LIG1 depletion that is sustained through the study. Image (A) and quantification (B) of western blotting data from tumors of immunodeficient mice grafted with MDA-MB-436 cells engineered to express a DOX-…
View article: Supplementary Figure S1 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers
Supplementary Figure S1 from LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers Open
Cell lines with damaging mutations in BRCA2 are dependent on LIG1. A) Analysis of DepMap data (28) comparing LIG1 dependence of cell lines with damaging mutations in BRCA2 vs. BRCA2 wild-type cell lines. ***p=0.0004 unpaired t-test. B,C) R…
View article: Discovery of TNG462: A Highly Potent and Selective MTA-Cooperative PRMT5 Inhibitor to Target Cancers with <i>MTAP</i> Deletion
Discovery of TNG462: A Highly Potent and Selective MTA-Cooperative PRMT5 Inhibitor to Target Cancers with <i>MTAP</i> Deletion Open
The gene encoding for MTAP is one of the most commonly deleted genes in cancer, occurring in approximately 10-15% of all human cancer. We have previously described the discovery of TNG908, a brain-penetrant clinical-stage compound that sel…
View article: LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers
LIG1 Is a Synthetic Lethal Target in <i>BRCA1</i> Mutant Cancers Open
Synthetic lethality approaches in BRCA1/2-mutated cancers have focused on PARP inhibitors, which are subject to high rates of innate or acquired resistance in patients. In this study, we used CRISPR/Cas9-based screening to identify DNA lig…
View article: Discovery of TNG908: A Selective, Brain Penetrant, MTA-Cooperative PRMT5 Inhibitor That Is Synthetically Lethal with <i>MTAP</i>-Deleted Cancers
Discovery of TNG908: A Selective, Brain Penetrant, MTA-Cooperative PRMT5 Inhibitor That Is Synthetically Lethal with <i>MTAP</i>-Deleted Cancers Open
It has been shown that PRMT5 inhibition by small molecules can selectively kill cancer cells with homozygous deletion of the MTAP gene if the inhibitors can leverage the consequence of MTAP deletion, namely, accumulation of the MTAP substr…