Andreas Joerger

Principal Investigator

Frankfurt

Andreas C. Joerger obtained his doctoral degree from the University of Freiburg, Germany in 2000 for elucidating the reaction mechanism and structural basis of substrate specificity of a zinc-dependent aldolase. He then assumed a postdoc position in the group of Prof. Sir Alan Fersht at the Medical Research Council (MRC) Centre for Protein Engineering in Cambridge, United Kingdom, initially working on protein design. He stayed on as a senior scientist in structural biology until 2010, before moving to the MRC Laboratory of Molecular Biology in Cambridge (2010-2015). During his long spell at the MRC, he made key contributions towards unraveling the complex structural biology of the tumor suppressor p53 and related proteins. He determined the first crystal structures of p53 cancer mutants, which led to the Y220C mutant being used as a paradigm for the development of mutant p53 rescue drugs based on protein stabilization. In 2016, Dr. Joerger joined the group of Prof. Stefan Knapp at the Institute of Pharmaceutical Chemistry at Goethe University, Frankfurt am Main. He is currently a German Research Foundation (DFG)-funded project leader on targeting the p53 mutome for cancer therapy; and co-investigator on a grant from Worldwide Cancer Research for the development of Y220C mutant stabilizers. His other research interests include the evolutionary history of the p53 pathway, epigenetic targets and general principles of molecular interactions.

Integrated analysis of Shank1 PDZ interactions with C-terminal and internal binding motifs.
Ali M, McAuley MM, Lüchow S, Knapp S, Joerger AC, Ivarsson Y
Curr Res Struct Biol. 2021 3:41-50. doi: 10.1016/j.crstbi.2021.01.001
PMID: 34235485

Structure-Based Design of Selective Salt-Inducible Kinase Inhibitors.
Tesch R, Rak M, Raab M, Berger LM, Kronenberger T, Joerger AC, Berger BT, Abdi I, Hanke T, Poso A, Strebhardt K, Sanhaji M, Knapp S
J Med Chem. 2021 . doi: 10.1021/acs.jmedchem.0c02144
PMID: 34086472

Genotoxicity and Epigenotoxicity of Carbazole-Derived Molecules on MCF-7 Breast Cancer Cells.
Luparello C, Cruciata I, Joerger AC, Ocasio CA, Jones R, Tareque RK, Bagley MC, Spencer J, Walker M, Austin C, Ferrara T, D Oca P, Bellina R, Branni R, Caradonna F
Int J Mol Sci. 2021 22(7):. doi: 10.3390/ijms22073410
PMID: 33810274

2024

Development of Potent Dual BET/HDAC Inhibitors via Pharmacophore Merging and Structure-Guided Optimization.
Bauer N, Balourdas DI, Schneider JR, Zhang X, Berger LM, Berger BT, Schwalm MP, Klopp NA, Siveke JT, Knapp S, Joerger AC
ACS Chem Biol. 31.01.2024 . doi: 10.1021/acschembio.3c00427
PMID: 38291964

2023

Synthesis of Pyrazole-Based Macrocycles Leads to a Highly Selective Inhibitor for MST3.
Amrhein JA, Berger LM, Balourdas DI, Joerger AC, Menge A, Krämer A, Frischkorn JM, Berger BT, Elson L, Kaiser A, Schubert-Zsilavecz M, Müller S, Knapp S, Hanke T
J Med Chem. 21.12.2023 . doi: 10.1021/acs.jmedchem.3c01980
PMID: 38126712

From cultivation to cancer: formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications.
Stanfill SB, Hecht SS, Joerger AC, González PJ, Maia LB, Rivas MG, Moura JJG, Gupta AK, Le Brun NE, Crack JC, Hainaut P, Sparacino-Watkins C, Tyx RE, Pillai SD, Zaatari GS, Henley SJ, Blount BC, Watson CH, Kaina B, Mehrotra R
Crit Rev Toxicol. 21.11.2023 1-44. doi: 10.1080/10408444.2023.2264327
PMID: 38050998

Structure-Reactivity Studies of 2-Sulfonylpyrimidines Allow Selective Protein Arylation.
Pichon MM, Drelinkiewicz D, Lozano D, Moraru R, Hayward LJ, Jones M, McCoy MA, Allstrum-Graves S, Balourdas DI, Joerger AC, Whitby RJ, Goldup SM, Wells N, Langley GJ, Herniman JM, Baud MGJ
Bioconjug Chem. 01.09.2023 . doi: 10.1021/acs.bioconjchem.3c00322
PMID: 37657082

Structural insights into a regulatory mechanism of FIR RRM1-FUSE interaction.
Ni X, Joerger AC, Chaikuad A, Knapp S
Open Biol. 31.05.2023 13(5):230031. doi: 10.1098/rsob.230031
PMID: 37253421

Shifting the selectivity of pyrido[2,3-d]pyrimidin-7(8H)-one inhibitors towards the salt-inducible kinase (SIK) subfamily.
Rak M, Tesch R, Berger LM, Shevchenko E, Raab M, Tjaden A, Zhubi R, Balourdas DI, Joerger AC, Poso A, Krämer A, Elson L, Lučić A, Kronenberger T, Hanke T, Strebhardt K, Sanhaji M, Knapp S
Eur J Med Chem. 07.04.2023 254:115347. doi: 10.1016/j.ejmech.2023.115347
PMID: 37094449

2022

Development of a Potent Cyclic Peptide Inhibitor of the nNOS/PSD-95 Interaction.
Balboa JR, Essig DJ, Ma S, Karer N, Clemmensen LS, Pedersen SW, Joerger AC, Knapp S, Østergaard S, Strømgaard K
J Med Chem. 29.12.2022 . doi: 10.1021/acs.jmedchem.2c01803
PMID: 36580549

Discovery of Nanomolar-Affinity Pharmacological Chaperones Stabilizing the Oncogenic p53 Mutant Y220C.
Stephenson Clarke JR, Douglas LR, Duriez PJ, Balourdas DI, Joerger AC, Khadiullina R, Bulatov E, Baud MGJ
ACS Pharmacol Transl Sci. 11.11.2022 5(11):1169-1180. doi: 10.1021/acsptsci.2c00164
PMID: 36407959

Evolutionary history of the p53 family DNA-binding domain: insights from an Alvinella pompejana homolog.
Zhang Q, Balourdas DI, Baron B, Senitzki A, Haran TE, Wiman KG, Soussi T, Joerger AC
Cell Death Dis. 07.03.2022 13(3):214. doi: 10.1038/s41419-022-04653-8
PMID: 35256607

2021

Development of a Selective Dual Discoidin Domain Receptor (DDR)/p38 Kinase Chemical Probe.
Röhm S, Berger BT, Schröder M, Chatterjee D, Mathea S, Joerger AC, Pinkas DM, Bufton JC, Tjaden A, Kovooru L, Kudolo M, Pohl C, Bullock AN, Müller S, Laufer S, Knapp S
J Med Chem. 10.09.2021 . doi: 10.1021/acs.jmedchem.1c00868
PMID: 34506142

Integrated analysis of Shank1 PDZ interactions with C-terminal and internal binding motifs.
Ali M, McAuley MM, Lüchow S, Knapp S, Joerger AC, Ivarsson Y
Curr Res Struct Biol. 09.07.2021 3:41-50. doi: 10.1016/j.crstbi.2021.01.001
PMID: 34235485

Structure-Based Design of Selective Salt-Inducible Kinase Inhibitors.
Tesch R, Rak M, Raab M, Berger LM, Kronenberger T, Joerger AC, Berger BT, Abdi I, Hanke T, Poso A, Strebhardt K, Sanhaji M, Knapp S
J Med Chem. 04.06.2021 . doi: 10.1021/acs.jmedchem.0c02144
PMID: 34086472

Genotoxicity and Epigenotoxicity of Carbazole-Derived Molecules on MCF-7 Breast Cancer Cells.
Luparello C, Cruciata I, Joerger AC, Ocasio CA, Jones R, Tareque RK, Bagley MC, Spencer J, Walker M, Austin C, Ferrara T, D Oca P, Bellina R, Branni R, Caradonna F
Int J Mol Sci. 26.03.2021 22(7):. doi: 10.3390/ijms22073410
PMID: 33810274

2020

Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene.
Doffe F, Carbonnier V, Tissier M, Leroy B, Martins I, Mattsson JSM, Micke P, Pavlova S, Pospisilova S, Smardova J, Joerger AC, Wiman KG, Kroemer G, Soussi T
Cell Death Differ. 02.12.2020 28(5):1477-1492. doi: 10.1038/s41418-020-00672-0
PMID: 33257846

Pan-SMARCA/PB1 Bromodomain Inhibitors and Their Role in Regulating Adipogenesis.
Wanior M, Preuss F, Ni X, Krämer A, Mathea S, Göbel T, Heidenreich D, Simonyi S, Kahnt AS, Joerger AC, Knapp S
J Med Chem. 10.12.2020 63(23):14680-14699. doi: 10.1021/acs.jmedchem.0c01242
PMID: 33216538

Selective targeting of the αC and DFG-out pocket in p38 MAPK.
Röhm S, Schröder M, Dwyer JE, Widdowson CS, Chaikuad A, Berger BT, Joerger AC, Krämer A, Harbig J, Dauch D, Kudolo M, Laufer S, Bagley MC, Knapp S
Eur J Med Chem. 20.08.2020 208:112721. doi: 10.1016/j.ejmech.2020.112721
PMID: 33035818

Characterization of a dual BET/HDAC inhibitor for treatment of pancreatic ductal adenocarcinoma.
Zhang X, Zegar T, Weiser T, Hamdan FH, Berger BT, Lucas R, Balourdas DI, Ladigan S, Cheung PF, Liffers ST, Trajkovic-Arsic M, Scheffler B, Joerger AC, Hahn SA, Johnsen SA, Knapp S, Siveke JT
Int. J. Cancer. 29.06.2020 . doi: 10.1002/ijc.33137
PMID: 32599645

Targeting Cavity-Creating p53 Cancer Mutations with Small-Molecule Stabilizers: the Y220X Paradigm.
Bauer MR, Krämer A, Settanni G, Jones RN, Ni X, Khan Tareque R, Fersht AR, Spencer J, Joerger AC
ACS Chem Biol. 20.03.2020 15(3):657-668. doi: 10.1021/acschembio.9b00748
PMID: 31990523

2019

A structure-guided molecular chaperone approach for restoring the transcriptional activity of the p53 cancer mutant Y220C.
Bauer MR, Jones RN, Tareque RK, Springett B, Dingler FA, Verduci L, Patel KJ, Fersht AR, Joerger AC, Spencer J
Future Med Chem. 22.10.2019 11(19):2491-2504. doi: 10.4155/fmc-2019-0181
PMID: 31633398

New pyrido[3,4-g]quinazoline derivatives as CLK1 and DYRK1A inhibitors: synthesis, biological evaluation and binding mode analysis.
Tazarki H, Zeinyeh W, Esvan YJ, Knapp S, Chatterjee D, Schröder M, Joerger AC, Khiari J, Josselin B, Baratte B, Bach S, Ruchaud S, Anizon F, Giraud F, Moreau P
Eur J Med Chem. 26.01.2019 166:304-317. doi: 10.1016/j.ejmech.2019.01.052
PMID: 30731399

2018

glqxz9283 sfy39587stf02 mnesdcuix8
sfy39587stf03