Shawna Leslie Organ

Discovery of the SMYD3 Inhibitor BAY-6035 Using Thermal Shift Assay (TSA)-Based High-Throughput Screening

Stefan Gradl, H. Steuber, Joerg Weiske, Magda Szewczyk et autres

SMYD3 (SET and MYND domain-containing protein 3) is a protein lysine methyltransferase that was initially described as an H3K4 methyltransferase involved in transcriptional regulation. SMYD3 has been reported to methylate and regulate several nonhistone proteins relevant to cancer, including mitogen-activated protein kinase …

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Author Correction: Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response

Magdalena M. Szewczyk, Yoshinori Ishikawa, Shawna Leslie Organ, Nozomu Sakai et autres

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response

Magdalena M. Szewczyk, Yoshinori Ishikawa, Shawna Leslie Organ, Nozomu Sakai et autres

Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective, and cell-active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, which in …

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Discovery of a chemical probe for PRDM9

Abdellah Allali‐Hassani, Magdalena M. Szewczyk, Danton Ivanochko, Shawna Leslie Organ et autres

Abstract PRDM9 is a PR domain containing protein which trimethylates histone 3 on lysine 4 and 36. Its normal expression is restricted to germ cells and attenuation of its activity results in altered meiotic gene transcription, impairment of double-stranded breaks and pairing …

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Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress responses

Magdalena M. Szewczyk, Yoshinori Ishikawa, Shawna Leslie Organ, Nozomu Sakai et autres

Abstract Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective and cell active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, …

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Abstract 1646: Discovery and characterization of BAY-6035, a novel benzodiazepine-based SMYD3 inhibitor

Stefan Gradl, H. Steuber, Jörg Weiske, Norbert Schmees et autres

Abstract SMYD3 (SET and MYND domain-containing protein 3) is a protein lysine methyltransferase (PKMT) which was initially described as H3K4 methyltransferase involved in transcriptional regulation. SMYD3 has recently been reported to methylate and regulate several non-histone cancer relevant proteins such as mitogen-activated …

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Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors

Jayme L. Dahlin, Kathryn M. Nelson, Jessica M. Strasser, Dalia Baršytė-Lovejoy et autres

Many compounds with potentially reactive chemical motifs and poor physicochemical properties are published as selective modulators of biomolecules without sufficient validation and then propagated in the scientific literature as useful chemical probes. Several histone acetyltransferase (HAT) inhibitors with these liabilities are now …

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TRIM14 is a Putative Tumor Suppressor and Regulator of Innate Immune Response in Non-Small Cell Lung Cancer

Josephine Hai, Chang‐Qi Zhu, Tao Wang, Shawna Leslie Organ et autres

Non-small-cell lung carcinoma (NSCLC) accounts for 85% of malignant lung tumors and is the leading cause of cancer deaths. Our group previously identified Tripartite Motif 14 (TRIM14) as a component of a prognostic multigene expression signature for NSCLC. Little is known about …

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ALARM NMR data - HAT inhibitors

Dahlin Jayme L., Kathryn M. Nelson, Jessica M. Strasser, Barsyte-Lovejoy Dalia et autres

Representative [1H-13C]-HMQC ALARM NMR spectra for reported histone acetyltransferase inhibitors. ALARM NMR is a protein-based NMR counter-screen for flagging potentially promiscuous and/or assay interference compounds in drug and chemical probe discovery. Human La antigen (50 uM final concentration) was incubated with reported …

ALARM NMR data - HAT inhibitors

Jayme L. Dahlin, Kathryn M. Nelson, Jessica M. Strasser, Dalia Baršytė-Lovejoy et autres

Representative [1H-13C]-HMQC ALARM NMR spectra for reported histone acetyltransferase inhibitors. ALARM NMR is a protein-based NMR counter-screen for flagging potentially promiscuous and/or assay interference compounds in drug and chemical probe discovery. Human La antigen (50 uM final concentration) was incubated with reported …

p120RasGAP Is a Mediator of Rho Pathway Activation and Tumorigenicity in the DLD1 Colorectal Cancer Cell Line

Shawna Leslie Organ, Josephine Hai, Nikolina Radulovich, Christopher B. Marshall et autres

KRAS is mutated in ∼40% of colorectal cancer (CRC), and there are limited effective treatments for advanced KRAS mutant CRC. Therefore, it is crucial that downstream mediators of oncogenic KRAS continue to be studied. We identified p190RhoGAP as being phosphorylated in the …

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c-MET and KRAS: Signalling and Clinical Implications in Colorectal Cancer

Shawna Leslie Organ

Colorectal cancer (CRC) is the third leading cause of death from cancer in North America. The KRAS gene is mutated in approximately 40-50% of all CRC, and this mutation precludes treatment with promising targeted therapeutics. c-MET is a receptor tyrosine kinase that …