Johannes C. Hermann

Abstract 4183: Finding Goldilocks: How AI-powered covalent drug discovery removes the “un” from “undruggable”

Johannes C. Hermann, Robert A. Everley, Han Wool Yoon, Rohan Varma et autres

Abstract Covalent drugs offer a path to drugging hard targets to provide urgently needed novel cancer medications. Starting from small covalent fragments is efficient in principle but difficult in practice due to challenges distinguishing generic from specific reactivity and the influence of …

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Abstract 5762: FMC-242, a highly potent and selective covalent inhibitor of the PI3Kα -RAS interaction, demonstrates robust anti-tumor activity as monotherapy and in combination with targeted therapies

Kevin R. Webster, Ryan McFadden, Abdul Awol, Koli Basu et autres

Abstract Activation of RAS and PI3Kα are the most frequent oncogenic events in cancer, playing a key role in many aspects of tumor cell physiology, including growth, survival, differentiation, and migration. While treatment options have recently emerged for a subset of KRAS …

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Structural basis for DCAF2 as a novel E3 ligase for PROTAC-mediated targeted protein degradation

Evan McMahon, Alexander G. Cioffi, Patrick R. Visperas, Michael B. Shaghafi et autres

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KS05.5.A REPETITIVE INTRACRANIAL INJECTION OF NATURAL KILLER CELLS ENGINEERED WITH A HER2-TARGETED CHIMERIC ANTIGEN RECEPTOR ALONE AND IN COMBINATION WITH SYSTEMIC ANTI-PD-1 CHECKPOINT INHIBITION IN PATIENTS WITH RECURRENT GLIOBLASTOMA

Michael C. Burger, Elisabeth Ehrend, F Straßheimer, Pinar Cakmak et autres

Abstract BACKGROUND Recurrent glioblastoma (GB) still carries a dismal prognosis with few established treatment options. In the multicenter CAR2BRAIN phase I first-in-human clinical trial, we investigated repetitive local adoptive transfer of clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2 alone and …

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Pathophysiologie des akuten Lungenversagens (ARDS)

Quirin Notz, Johannes C. Hermann, Ralf M. Muellenbach, Christopher Lotz

Acute respiratory distress syndrome (ARDS) is a common condition in intensive care medicine. Various intra- and extrapulmonal causes may trigger an epithelial and endothelial permeability increase, which leads to impaired gas exchange due to fluid overload of the alveoli and transmigration of …

Abstract 5333: Combining chemoproteomics with machine learning identifies functionally active covalent fragments for hard-to-drug cancer drivers

Johannes C. Hermann, Robert A. Everley, Laura J. Marholz, Matthew J. Berberich et autres

Abstract a) Many cancer drivers are considered “undruggable” and without targeted treatments because they lack binding sites for conventional small molecules. Here, we introduce The FRONTIER™ Platform applying machine learning (ML), chemoproteomics and covalent chemistry to identify binding sites and cell-active covalent …

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Abstract 1142: Discovery of FMC-376 a novel orally bioavailable inhibitor of activated KRASG12C

Snahel Patel, Barun Bhhatarai, Philamer Calses, Daniel Erlanson et autres

Abstract KRAS is one of the most frequently mutated genes in cancer and was long considered undruggable until the recent discovery of inhibitors that bind the inactive (GDP-bound) form of KRASG12C. The most clinically advanced of these first-generation molecules have demonstrated clinical …

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Supplementary Table 1 from Quantitative Chemical Proteomics Profiling Differentiates Erlotinib from Gefitinib in EGFR Wild-Type Non–Small Cell Lung Carcinoma Cell Lines

Angélique Augustin, Jens Lamerz, Hélène Meistermann, Sabrina Golling et autres

XLSX file - 144K, Protein identifications in eluted fractions from erlotinib-Sepharose and gefitinib-Sepharose

Supplementary Table 1 from Quantitative Chemical Proteomics Profiling Differentiates Erlotinib from Gefitinib in EGFR Wild-Type Non–Small Cell Lung Carcinoma Cell Lines

Angélique Augustin, Jens Lamerz, Hélène Meistermann, Sabrina Golling et autres

XLSX file - 144K, Protein identifications in eluted fractions from erlotinib-Sepharose and gefitinib-Sepharose

Supplementary Figure 2 from Quantitative Chemical Proteomics Profiling Differentiates Erlotinib from Gefitinib in EGFR Wild-Type Non–Small Cell Lung Carcinoma Cell Lines

Angélique Augustin, Jens Lamerz, Hélène Meistermann, Sabrina Golling et autres

XLSX file - 24K, Statistics of proteins that significantly decrease in their relative abundance with increasing compound concentration, in at least one of the two compounds

Supplementary Figure 1 from Quantitative Chemical Proteomics Profiling Differentiates Erlotinib from Gefitinib in EGFR Wild-Type Non–Small Cell Lung Carcinoma Cell Lines

Angélique Augustin, Jens Lamerz, Hélène Meistermann, Sabrina Golling et autres

PDF file - 60K, Schematic diagram of the experimental framework applied to perform label-free, quantitative chemical proteomics on erlotinib and gefitinib

Supplementary Figure 1 from Quantitative Chemical Proteomics Profiling Differentiates Erlotinib from Gefitinib in EGFR Wild-Type Non–Small Cell Lung Carcinoma Cell Lines

Angélique Augustin, Jens Lamerz, Hélène Meistermann, Sabrina Golling et autres

PDF file - 60K, Schematic diagram of the experimental framework applied to perform label-free, quantitative chemical proteomics on erlotinib and gefitinib