Jay H. Chung

MassIVE MSV000102593 - VDAC1 is the redox sensor that drives mitochondrial dysfunction and MASH

Jay H. Chung

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Clotting the Gap Between Mitochondria-Mediated Immunity and Mitochondrial Transfer

Florian Tupin, Jorge A. González-Chapa, Jay H. Chung, Christian Lood et autres

Mitochondria are organelles that orchestrate numerous cell functions in addition to providing energy. During viral infection or in case of defects in mitochondrial replication, an intricate mechanism of self-destruction is engaged through the formation of mitochondrial pores. This leads to the release …

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Abstract 7074: PLX-61639, a potent and orally bioavailable SMARCA2-selective monovalent direct degrader, enhances efficacy of standard of care agents in SMARCA4 mutant tumor models.

G. Parker, Geoffray Leriche, Aleksandar Jamborcic, Taylor Kampert et autres

Abstract SMARCA2 and SMARCA4 are mutually exclusive, essential catalytic subunits of human BAF complexes, which are involved in controlling gene expression through the remodeling of chromatin structure. In a subset of solid tumors, SMARCA4 is frequently mutated, rendering cancer cells with SMARCA4 …

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Abstract 4600: Discovery of PLX-66140, a first-in-class, potent and selective CDK2 molecular glue degrader for CCNE1-amplified tumors

Leenus Martin, Jean-François Brazeau, Nasrin Rastgoo, Quinn Spalding et autres

Abstract Introduction: Dysregulation of the cell cycle is a hallmark of many cancers. The Cyclin-Dependent Kinases (CDKs) with their cyclin binding partners are associated with cell cycle progression and transcriptional regulation. Targeting CDK2 is a key therapeutic strategy in oncology, especially in …

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Trex1 overexpression leads to longer lifespans and fragmented sleep in Drosophila melanogaster

Jeonghan Kim, Stephanie Mao, Y. Serrano Negron, Shailesh Kumar et autres

Abstract Three-prime repair exonuclease 1 (Trex1) prevents cytosolic DNA accumulation and immune activation, yet the physiological consequences of increased Trex1 expression in vivo remain unclear. In this study, we used Drosophila melanogaster, a model well suited for quantitative analyses of aging, sleep, …

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Selective inhibition of long isoforms of phosphodiesterase 4D mitigates liver fibrosis in mouse models

Jeonghan Kim, Heeeun Yoon, Seoung Chan Joe, Antoine Smith et autres

Chronic inflammation leads to tissue fibrosis, which can disrupt the function of the parenchyma of the organ and ultimately lead to organ failure. The most prevalent form of this occurs in chronic hepatitis, which leads to liver fibrosis and, ultimately, cirrhosis and …

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Abstract A026: Discovery of potent and selective CDK2 molecule glue degraders for the treatment of HR+/HER2- breast cancer, and CCNE1 amplified tumors

Nasrin Rastgoo, L-A Martin, Jean-François Brazeau, Quinn Spalding et autres

Abstract Introduction: The Cyclin-Dependent Kinase 2 (CDK2) is a key oncology target and promotes cell cycle progression by binding to its cyclin binding partners, especially, Cyclin E (CCNE1). The activated CCNE1/CDK2 complex phosphorylates RB and promotes cellular proliferation. CCNE1 amplification/overexpression drives aberrant …

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Adipose microsomal triglyceride transfer protein deficiency protects against hepatic steatosis by upregulating PPARα activity

Sujith Rajan, Michael Verano, Thomas Palaia, Chandana Prakashmurthy et autres

Background & Aim Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health issue. Identifying factors that prevent hepatic lipid accumulation could inform new MASLD prevention or treatment strategies. We previously demonstrated that adipocyte microsomal triglyceride transfer protein (MTP) regulates intracellular lipolysis …

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Abstract 2745: Identification of a selective and orally bioavailable BPTF PROTAC with anti-tumor activity in SWI/SNF mutant lung cancer

Wen Yan, Jay H. Chung, Denis E. Reyna, Dan Sherman et autres

Abstract BPTF is a bromodomain and PHD finger domain-containing protein that serves as a scaffolding subunit of the ISWI family member NURF chromatin remodeling complex. Together with interchangeable catalytic subunits SMARCA1 and SMARCA5 and additional subunits RBBP4, RBBP7, the NURF complex catalyzes …

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Abstract 1653: Preclinical characterization of PLX-61639, a potent and orally bioavailable SMARCA2-selective monovalent direct degrader

G.J. Parker, Geoffray Leriche, Aleksandar Jamborcic, Taylor Kampert et autres

Abstract SMARCA2 and SMARCA4 are essential, yet redundant, catalytic subunits of human BAF complexes, which are involved in controlling gene expression through the remodeling of chromatin structure. In a subset of solid tumors, SMARCA4 is commonly mutated, rendering SMARCA4-deficient cancer cells highly …

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Abstract 6380: PLX-4545, a selective IKZF2 degrader, reprograms suppressive Tregs leading to tumor growth inhibition and combination benefit with immune checkpoint therapy

Yujun Huang, SUSAN L. SONG, Linette Yang, Jianguo Ma et autres

Abstract Background: Checkpoint inhibitors (CPI) have significantly advanced cancer treatment; however, responses are limited to patient subsets. Tumors avoid immunosurveillance by recruiting suppressive regulatory T-cells (Treg) limiting the activation and expansion of tumor effector T-cells (Teff). The transcription factor IKZF2 (Helios) is …

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Abstract 6375: Discovery and characterization of novel, potent and selective CDK2 molecular glue degrader against CCNE1-amplified tumors

L-A Martin, Nasrin Rastgoo, Jean-François Brazeau, Quinn Spalding et autres

Abstract Introduction: The Cyclin-Dependent Kinases (CDKs) with their cyclin binding partners are associated with cell cycle progression and transcriptional regulation. Dysregulation of the cell cycle is a hallmark of cancer and targeting CDKs is a key oncology therapeutic strategy. Cyclin E1 (CCNE1) …

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