L.M. Stunkard

Abstract 5869: Preclinical characterization of CGT4255, an EGFR sparing, pan-mutant HER2 clinical development candidate with potential best-in-class brain penetration

Paul D. Larsen, Tanna Bettendorf, Abiezer Blandon, Karyn Bouhana et autres

Abstract HER2 alterations including amplification, overexpression, insertions, and point mutations are established oncogenic drivers across various solid tumor types. HER2 is amplified or overexpressed in 15-20% of breast cancer patients. In contrast, activating mutations are found in approximately 4% of cases with …

Abstract P4-12-19: Preclinical Characterization of a Novel PI3Kα H1047R Mutant-Selective Inhibitor

Aaron C. T. Smith, Ben Arwood-Levine, Abiezer Blandon, Alexandra Born et autres

Abstract PIK3CA encodes the p110α catalytic subunit of PI3-kinase alpha (PI3Kα) and is the most frequently mutated kinase in human cancer with common mutations occurring in the kinase domain (H1047R) and helical domain (E542K/E545K). The approved PI3Kα inhibitor, alpelisib, shows promise for …

Abstract P4-12-16: Identification of CGT4255 an EGFR sparing, ErbB2 clinical development candidate with activity across activating mutations in systemic and CNS tumors

Mark Joseph Chicarelli, Tanna Bettendorf, Abiezer Blandon, Karyn Bouhana et autres

Abstract Alterations in ErbB2, including amplification, overexpression, insertions, and point mutations, are established oncogenic drivers in many solid tumors. These mutations are found in approximately 3–4% of breast cancers and 3% of advanced lung cancers and have emerged as mechanisms of acquired …

Abstract 5623: Identification of CGT4255 an EGFR sparing, pan-mutant HER2 clinical development candidate with potential best-in-class brain penetration

Mark Joseph Chicarelli, Tanna Bettendorf, Abiezer Blandon, Karyn Bouhana et autres

Abstract HER2 alterations such as amplification, overexpression, insertions, and point mutations, are established oncogenic drivers in many solid tumors. Activating HER2 mutations are found in 2-4% of advanced lung cancers and have emerged as mechanisms of acquired resistance to targeted therapies. Patients …

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Abstract 3004: Preclinical characterization of CGT6297, a novel PI3Kα H1047R mutant-selective inhibitor

Aaron C. T. Smith, Ben Arwood-Levine, Abiezer Blandon, Alexandra Born et autres

Abstract PIK3CA encodes the p110α catalytic subunit of PI3-kinase alpha (PI3Kα) and is the most frequently mutated kinase in human cancer with common mutations occurring in the kinase domain (H1047R) and helical domain (E542K/E545K). The approved PI3Kα inhibitor, alpelisib, shows promise for …

145 (PB133): Preclinical characterization of a novel PI3Kα H1047R mutant-selective inhibitor

Alison C. Smith, Ben Arwood-Levine, Alexandra Born, Pratishtha Chatterjee et autres

Abstract PO3-26-01: Preclinical in vitro and in vivo characterization of a novel, wild-type-sparing, PI3Kα H1047R mutant-selective inhibitor

Aaron C. T. Smith, Ben Arwood-Levine, Alexandra Born, Richard K. Brizendine et autres

Abstract The PI3K pathway is a key cell cycle regulating pathway that has an established role in tumor growth and development. Specifically, the H1047R and helical domain mutations E542K/E545K of the p110α subunit of PI3K are known activating mutations that are targeted …

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Abstract PO3-26-02: Identification of a novel, brain penetrant, EGFR sparing, ErbB2 inhibitor with activity against oncogenic ErbB2 mutations

Mark Joseph Chicarelli, Ben Arwood-Levine, Tanna Bettendorf, Karyn Bouhana et autres

Abstract Alterations in ErbB2 have an established role as oncogenic drivers in many solid tumors, including gastric and breast cancer. While ErbB2 amplification is well recognized, activating ErbB2 mutations including exon 20 YVMA insertions, S310F/Y, L755S, V777L, and V842I, have emerged as …

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Abstract 4486: Characterization of a novel mutant selective, EGFR sparing, ErbB2 inhibitor with activity across activating mutations in systemic and CNS tumors

Jennifer Fulton, Tanna Bettendorf, Abiezer Blandon, Karyn Bouhana et autres

Abstract Alterations in ErbB2, including amplification, overexpression, insertions, and point mutations, are established oncogenic drivers in many solid tumors. These mutations are found in approximately 3-4% of breast cancers and 3% of advanced lung cancers and have emerged as mechanisms of acquired …

Abstract 1440: Identification of a novel EGFR sparing brain penetrant ErbB2 inhibitor with activity against oncogenic ErbB2 mutations

Mark Joseph Chicarelli, Karyn Bouhana, Richard K. Brizendine, LouAnn Cable et autres

Abstract Oncogenic driver mutations in ErbB2 (e.g., S310F/Y, L755S, V777L, V842I) are present in a variety of tumor types including gastric, uterine, urothelial carcinoma, non-small cell lung, breast, and colorectal, some of which are also known to metastasize to the CNS. These …

Structures of chloramphenicol acetyltransferase III and Escherichia coli β-ketoacylsynthase III co-crystallized with partially hydrolysed acetyl-oxa(dethia)CoA

Aaron B. Benjamin, L.M. Stunkard, Jianheng Ling, Jaelen N. Nice et autres

Acetyl coenzyme A (acetyl-CoA) is a reactive metabolite that nonproductively hydrolyzes in a number of enzyme active sites in the crystallization time frame. In order to elucidate the enzyme-acetyl-CoA interactions leading to catalysis, acetyl-CoA substrate analogs are needed. One possible analog for …

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Activity of Fatty Acid Biosynthesis Initiating Ketosynthase FabH with Acetyl/Malonyl-oxa/aza(dethia)CoAs

Trevor J. Boram, Aaron B. Benjamin, Amanda Silva de Sousa, L.M. Stunkard et autres

Fatty acid and polyketide biosynthetic enzymes exploit the reactivity of acyl- and malonyl-thioesters for catalysis. A prime example is FabH, which initiates fatty acid biosynthesis in many bacteria and plants. FabH performs an acyltransferase reaction with acetyl-CoA to generate an acetyl- S …

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