@article{MTMT:34445373,
	title = {Electrophilic MiniFrags Revealed Unprecedented Binding Sites for Covalent HDAC8 Inhibitors},
	url = {https://m2.mtmt.hu/api/publication/34445373},
	author = {Keeley, Aaron Brian and Kopranovic, Aleksandra and Di Lorenzo, Vincenzo and Ábrányi-Balogh, Péter and Jänsch, Niklas and Lai, Linh N. and Petri, László and Orgován, Zoltán and Pölöske, Daniel and Orlova, Anna and Németh, András György and Desczyk, Charlotte and Imre, Timea and Bajusz, Dávid and Moriggl, Richard and Meyer-Almes, Franz-Josef and Keserű, György Miklós},
	doi = {10.1021/acs.jmedchem.3c01779},
	journal-iso = {J MED CHEM},
	journal = {JOURNAL OF MEDICINAL CHEMISTRY},
	volume = {67},
	unique-id = {34445373},
	issn = {0022-2623},
	abstract = {Screening of ultra-low-molecular weight ligands (MiniFrags) successfully identified viable chemical starting points for a variety of drug targets. Here we report the electrophilic analogues of MiniFrags that allow the mapping of potential binding sites for covalent inhibitors by biochemical screening and mass spectrometry. Small electrophilic heterocycles and their N-quaternized analogues were first characterized in the glutathione assay to analyze their electrophilic reactivity. Next, the library was used for systematic mapping of potential covalent binding sites available in human histone deacetylase 8 (HDAC8). The covalent labeling of HDAC8 cysteines has been proven by tandem mass spectrometry measurements, and the observations were explained by mutating HDAC8 cysteines. As a result, screening of electrophilic MiniFrags identified three potential binding sites suitable for the development of allosteric covalent HDAC8 inhibitors. One of the hit fragments was merged with a known HDAC8 inhibitor fragment using different linkers, and the linker length was optimized to result in a lead-like covalent inhibitor. © 2023 The Authors. Published by American Chemical Society},
	year = {2024},
	eissn = {1520-4804},
	pages = {572-585},
	orcid-numbers = {Di Lorenzo, Vincenzo/0000-0002-3140-3561; Bajusz, Dávid/0000-0003-4277-9481; Meyer-Almes, Franz-Josef/0000-0002-1001-3249}
}

@mastersthesis{MTMT:34738155,
	title = {Computational investigation of the allosteric modulation of metabotropic glutamate receptor 5},
	url = {https://m2.mtmt.hu/api/publication/34738155},
	author = {Orgován, Zoltán},
	publisher = {Budapest University of Technology and Economics},
	unique-id = {34738155},
	year = {2023}
}

@article{MTMT:33647485,
	title = {Covalent fragment mapping of KRasG12C revealed novel chemotypes with in vivo potency},
	url = {https://m2.mtmt.hu/api/publication/33647485},
	author = {Orgován, Zoltán and Péczka, Nikolett and Petri, László and Ábrányi-Balogh, Péter and Randelovic, Ivan and Tóth, Szilárd and Szakács, Gergely and Nyíri, Kinga and Vértessy, Beáta (Grolmuszné) and Pálfy, Gyula and Vida, István and Perczel, András and Tóvári, József and Keserű, György Miklós},
	doi = {10.1016/j.ejmech.2023.115212},
	journal-iso = {EUR J MED CHEM},
	journal = {EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY},
	volume = {250},
	unique-id = {33647485},
	issn = {0223-5234},
	abstract = {G12C mutant KRas is considered druggable by allele-specific covalent inhibitors due to the nucleophilic character of the oncogenic mutant cysteine at position 12. Discovery of these inhibitors requires the optimization of both covalent and noncovalent interactions. Here, we report covalent fragment screening of our electrophilic fragment library of diverse non-covalent scaffolds equipped with 40 different electrophilic functionalities to identify fragments as suitable starting points targeting Cys12. Screening the library against KRasG12C using Ellman's free thiol assay, followed by protein NMR and cell viability assays, resulted in two potential inhibitor chemotypes. Characterization of these scaffolds in in vitro cellular- and in vivo xenograft models revealed them as promising starting points for covalent drug discovery programs.},
	year = {2023},
	eissn = {1768-3254},
	orcid-numbers = {Randelovic, Ivan/0000-0003-0161-0022; Pálfy, Gyula/0000-0003-1590-5331; Perczel, András/0000-0003-1252-6416; Tóvári, József/0000-0002-5543-3204}
}

@article{MTMT:33307131,
	title = {A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase–meropenem complex},
	url = {https://m2.mtmt.hu/api/publication/33307131},
	author = {Kiss-Szemán, Anna Júlia and Takács, Luca and Orgován, Zoltán and Stráner, Pál and Jákli, Imre and Schlosser, Gitta (Vácziné) and Masiulis, Simonas and Harmat, Veronika and Karancsiné Menyhárd, Dóra and Perczel, András},
	doi = {10.1039/D2SC05520A},
	journal-iso = {CHEM SCI},
	journal = {CHEMICAL SCIENCE},
	volume = {13},
	unique-id = {33307131},
	issn = {2041-6520},
	abstract = {The structure of porcine AAP (pAAP) in a covalently bound complex with meropenem was determined by cryo-EM to 2.1 Å resolution, showing the mammalian serine-protease inhibited by a carbapenem antibiotic.},
	year = {2022},
	eissn = {2041-6539},
	pages = {14264-14276},
	orcid-numbers = {Kiss-Szemán, Anna Júlia/0000-0002-3039-0324; Takács, Luca/0000-0002-4864-8872; Stráner, Pál/0000-0003-2240-8501; Schlosser, Gitta (Vácziné)/0000-0002-7637-7133; Harmat, Veronika/0000-0002-1866-9904; Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Perczel, András/0000-0003-1252-6416}
}

@article{MTMT:32756662,
	title = {Electrophilic warheads in covalent drug discovery: an overview},
	url = {https://m2.mtmt.hu/api/publication/32756662},
	author = {Péczka, Nikolett and Orgován, Zoltán and Ábrányi-Balogh, Péter and Keserű, György Miklós},
	doi = {10.1080/17460441.2022.2034783},
	journal-iso = {EXPERT OPIN DRUG DIS},
	journal = {EXPERT OPINION ON DRUG DISCOVERY},
	volume = {17},
	unique-id = {32756662},
	issn = {1746-0441},
	year = {2022},
	eissn = {1746-045X},
	pages = {413-422}
}

@article{MTMT:31698584,
	title = {Allosteric Molecular Switches in Metabotropic Glutamate Receptors},
	url = {https://m2.mtmt.hu/api/publication/31698584},
	author = {Orgován, Zoltán and Ferenczy, György and Keserű, György Miklós},
	doi = {10.1002/cmdc.202000444},
	journal-iso = {CHEMMEDCHEM},
	journal = {CHEMMEDCHEM},
	volume = {16},
	unique-id = {31698584},
	issn = {1860-7179},
	abstract = {Metabotropic glutamate receptors (mGlu) are class C G protein-coupled receptors of eight subtypes that are omnipresently expressed in the central nervous system. mGlus have relevance in several psychiatric and neurological disorders, therefore they raise considerable interest as drug targets. Allosteric modulators of mGlus offer advantages over orthosteric ligands owing to their increased potential to achieve subtype selectivity, and this has prompted discovery programs that have produced a large number of reported allosteric mGlu ligands. However, the optimization of allosteric ligands into drug candidates has proved to be challenging owing to induced-fit effects, flat or steep structure-activity relationships and unexpected changes in theirpharmacology. Subtle structural changes identified as molecular switches might modulate the functional activity of allosteric ligands. Here we review these switches discovered in the metabotropic glutamate receptor family..},
	keywords = {METABOTROPIC GLUTAMATE RECEPTORS; Allosteric modulation; MOLECULAR SWITCHES; GPCRs; water networks},
	year = {2021},
	eissn = {1860-7187},
	pages = {81-93},
	orcid-numbers = {Ferenczy, György/0000-0002-5771-4616}
}

@article{MTMT:30834454,
	title = {Allosteric activation of metabotropic glutamate receptor 5},
	url = {https://m2.mtmt.hu/api/publication/30834454},
	author = {Jójárt, Balázs and Orgován, Zoltán and Márki, Árpád and Pándy-Szekeres, Gáspár and Ferenczy, György and Keserű, György Miklós},
	doi = {10.1080/07391102.2019.1638302},
	journal-iso = {J BIOMOL STRUCT DYN},
	journal = {JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS},
	volume = {38},
	unique-id = {30834454},
	issn = {0739-1102},
	year = {2020},
	eissn = {1538-0254},
	pages = {2624-2632},
	orcid-numbers = {Márki, Árpád/0000-0002-6056-8891; Ferenczy, György/0000-0002-5771-4616}
}

@article{MTMT:31605838,
	title = {Structural impact of GTP binding on downstream KRAS signaling},
	url = {https://m2.mtmt.hu/api/publication/31605838},
	author = {Karancsiné Menyhárd, Dóra and Pálfy, Gyula and Orgován, Zoltán and Vida, István and Keserű, György Miklós and Perczel, András},
	doi = {10.1039/d0sc03441j},
	journal-iso = {CHEM SCI},
	journal = {CHEMICAL SCIENCE},
	volume = {11},
	unique-id = {31605838},
	issn = {2041-6520},
	abstract = {Oncogenic RAS proteins, involved in similar to 30% of human tumors, are molecular switches of various signal transduction pathways. Here we apply a new protocol for the NMR study of KRAS in its (inactive) GDP- and (activated) GTP-bound form, allowing a comprehensive analysis of the backbone dynamics of its WT-, G12C- and G12D variants. We found that Tyr32 shows opposite mobility with respect to the backbone of its surroundings: it is more flexible in the GDP-bound form while more rigid in GTP-complexes (especially in WT- and G12D-GTP). Using the G12C/Y32F double mutant, we showed that the presence of the hydroxyl group of Tyr32 has a marked effect on the G12C-KRAS-GTP system as well. Molecular dynamics simulations indicate that Tyr32 is linked to the gamma-phosphate of GTP in the activated states - an arrangement shown, using QM/MM calculations, to support catalysis. Anchoring Tyr32 to the gamma-phosphate contributes to the capture of the catalytic waters participating in the intrinsic hydrolysis of GTP and supports a simultaneous triple proton transfer step (catalytic water -> assisting water -> Tyr32 -> O1G of the gamma-phosphate) leading to straightforward product formation. The coupled flip of negatively charged residues of switch I toward the inside of the effector binding pocket potentiates ligand recognition, while positioning of Thr35 to enter the coordination sphere of the Mg(2+)widens the pocket. Position 12 mutations do not disturb the capture of Tyr32 by the gamma-phosphate, but (partially) displace Gln61, which opens up the catalytic pocket and destabilizes catalytic water molecules thus impairing intrinsic hydrolysis.},
	keywords = {ACTIVATION; MODEL-FREE APPROACH; HYDROLYSIS; RAS; MAGNETIC-RESONANCE RELAXATION; BACKBONE DYNAMICS; HOT-SPOTS; conformational ensembles; MOLECULAR SWITCH},
	year = {2020},
	eissn = {2041-6539},
	pages = {9272-9289},
	orcid-numbers = {Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Pálfy, Gyula/0000-0003-1590-5331; Perczel, András/0000-0003-1252-6416}
}

@article{MTMT:31473660,
	title = {Small molecule inhibitors of RAS proteins with oncogenic mutations},
	url = {https://m2.mtmt.hu/api/publication/31473660},
	author = {Orgován, Zoltán and Keserű, György Miklós},
	doi = {10.1007/s10555-020-09911-9},
	journal-iso = {CANCER METAST REV},
	journal = {CANCER AND METASTASIS REVIEWS},
	volume = {39},
	unique-id = {31473660},
	issn = {0167-7659},
	abstract = {RAS proteins control a number of essential cellular processes as molecular switches in the human body. Presumably due to their important signalling role, RAS proteins are among the most frequently mutated oncogenes in human cancers. Hence, numerous efforts were done to develop appropriate therapies for RAS-mutant cancers in the last three decades. This review aimed to collect all of the reported small molecules that affect RAS signalling. These molecules can be divided in four main branches. First, we address approaches blocking RAS membrane association. Second, we focus on the stabilization efforts of non-productive RAS complexes. Third, we examine the approach to block RAS downstream signalling through disturbance of RAS-effector complex formation. Finally, we discuss direct inhibition; particularly the most recently reported covalent inhibitors, which are already advanced to human clinical trials. © 2020, The Author(s).},
	keywords = {ras Proteins; GTPASES; Oncogenic mutations; Small molecular inhibitors},
	year = {2020},
	eissn = {1573-7233},
	pages = {1107-1126}
}

@article{MTMT:30928052,
	title = {Discovery of dihydropyrazino-benzimidazole derivatives as metabotropic glutamate receptor-2 (mGluR2) positive allosteric modulators (PAMs)},
	url = {https://m2.mtmt.hu/api/publication/30928052},
	author = {Szabó, György and Kolok, Sándor and Orgován, Zoltán and Vastag, Monika and Béni, Zoltán and Kóti, János and Sághy, Katalin and Lévay, György István and Greiner, István and Keserű, György Miklós},
	doi = {10.1016/j.ejmech.2019.111881},
	journal-iso = {EUR J MED CHEM},
	journal = {EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY},
	volume = {186},
	unique-id = {30928052},
	issn = {0223-5234},
	year = {2020},
	eissn = {1768-3254},
	orcid-numbers = {Szabó, György/0000-0002-9255-4486; Béni, Zoltán/0000-0002-1275-4155; Keserű, György Miklós/0000-0003-1039-7809}
}

@article{MTMT:30334026,
	title = {Structure-Based Optimization Strategies for G Protein-Coupled Receptor (GPCR) Allosteric Modulators: A Case Study from Analyses of New Metabotropic Glutamate Receptor 5 (mGlu 5 ) X-ray Structures},
	url = {https://m2.mtmt.hu/api/publication/30334026},
	author = {Christopher, John A. and Orgován, Zoltán and Congreve, Miles and Doré, Andrew S. and Errey, James C. and Marshall, Fiona H. and Mason, Jonathan S. and Okrasa, Krzysztof and Rucktooa, Prakash and Serrano-Vega, Maria J. and Ferenczy, György and Keserű, György Miklós},
	doi = {10.1021/acs.jmedchem.7b01722},
	journal-iso = {J MED CHEM},
	journal = {JOURNAL OF MEDICINAL CHEMISTRY},
	volume = {62},
	unique-id = {30334026},
	issn = {0022-2623},
	year = {2019},
	eissn = {1520-4804},
	pages = {207-222},
	orcid-numbers = {Ferenczy, György/0000-0002-5771-4616}
}

@article{MTMT:31038395,
	title = {Allélspecifikus inhibitorok nyomában: a RASopátia konzorcium célpontjában a KRAS fehérje onkogén mutációi},
	url = {https://m2.mtmt.hu/api/publication/31038395},
	author = {Nyíri, Kinga and Koppány, Gergely and Pálfy, Gyula and Vida, István and Tóth, Szilárd and Orgován, Zoltán and Randelovic, Ivan and Baranyi, Marcell and Molnár, Eszter and Keserű, György Miklós and Tóvári, József and Perczel, András and Vértessy, Beáta (Grolmuszné) and Tímár, József},
	journal-iso = {MAGYAR ONKOLÓGIA},
	journal = {MAGYAR ONKOLÓGIA},
	volume = {63},
	unique-id = {31038395},
	issn = {0025-0244},
	year = {2019},
	eissn = {2060-0399},
	pages = {310-323},
	orcid-numbers = {Pálfy, Gyula/0000-0003-1590-5331; Randelovic, Ivan/0000-0003-0161-0022; Molnár, Eszter/0000-0002-4745-2018; Tóvári, József/0000-0002-5543-3204; Tímár, József/0000-0001-9183-0859}
}

@article{MTMT:30834430,
	title = {Fragment-Based Approaches for Allosteric Metabotropic Glutamate Receptor (mGluR) Modulators},
	url = {https://m2.mtmt.hu/api/publication/30834430},
	author = {Orgován, Zoltán and Ferenczy, György and Keserű, György Miklós},
	doi = {10.2174/1568026619666190808150039},
	journal-iso = {CURR TOP MED CHEM},
	journal = {CURRENT TOPICS IN MEDICINAL CHEMISTRY},
	volume = {19},
	unique-id = {30834430},
	issn = {1568-0266},
	year = {2019},
	eissn = {1873-4294},
	pages = {1768-1781},
	orcid-numbers = {Ferenczy, György/0000-0002-5771-4616}
}

@article{MTMT:30834424,
	title = {The role of water and protein flexibility in the structure-based virtual screening of allosteric GPCR modulators: an mGlu5 receptor case study},
	url = {https://m2.mtmt.hu/api/publication/30834424},
	author = {Orgován, Zoltán and Ferenczy, György and Keserű, György Miklós},
	doi = {10.1007/s10822-019-00224-w},
	journal-iso = {J COMPUT AID MOL DES},
	journal = {JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN},
	volume = {33},
	unique-id = {30834424},
	issn = {0920-654X},
	year = {2019},
	eissn = {1573-4951},
	pages = {787-797},
	orcid-numbers = {Ferenczy, György/0000-0002-5771-4616}
}

@article{MTMT:3333356,
	title = {Validation of tautomeric and protomeric binding modes by free energy calculations. A case study for the structure based optimization of d-amino acid oxidase inhibitors},
	url = {https://m2.mtmt.hu/api/publication/3333356},
	author = {Orgován, Zoltán and Ferenczy, György and Steinbrecher, Thomas and Szilágyi, Bence and Bajusz, Dávid and Keserű, György Miklós},
	doi = {10.1007/s10822-018-0097-y},
	journal-iso = {J COMPUT AID MOL DES},
	journal = {JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN},
	volume = {32},
	unique-id = {3333356},
	issn = {0920-654X},
	year = {2018},
	eissn = {1573-4951},
	pages = {331-345},
	orcid-numbers = {Ferenczy, György/0000-0002-5771-4616; Bajusz, Dávid/0000-0003-4277-9481}
}

@article{MTMT:3291826,
	title = {Discovery of 4-amino-3-arylsulfoquinolines, a novel non-acetylenic chemotype of metabotropic glutamate 5 (mGlu5) receptor negative allosteric modulators},
	url = {https://m2.mtmt.hu/api/publication/3291826},
	author = {Galambos, J and Bielik, A and Wágner, G and Domány, G and Kóti, János and Béni, Zoltán and Szigetvári, Á and Sánta, Z and Orgován, Zoltán and Bobok, A and Kiss, Béla and Mikó-Bakk, ML and Vastag, M and Sághy, K and Krasavin, M and Gál, K and Greiner, István and Szombathelyi, Zsolt and Keserű, György Miklós},
	doi = {10.1016/j.ejmech.2017.03.071},
	journal-iso = {EUR J MED CHEM},
	journal = {EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY},
	volume = {133},
	unique-id = {3291826},
	issn = {0223-5234},
	year = {2017},
	eissn = {1768-3254},
	pages = {240-254},
	orcid-numbers = {Béni, Zoltán/0000-0002-1275-4155}
}

@article{MTMT:3291825,
	title = {Discovery and Preclinical Characterization of 3-((4-(4-Chlorophenyl)-7-fluoroquinoline-3-yl)sulfonyl)benzonitrile, a Novel Non-acetylenic Metabotropic Glutamate Receptor 5 (mGluR5) Negative Allosteric Modulator for Psychiatric Indications},
	url = {https://m2.mtmt.hu/api/publication/3291825},
	author = {Galambos, J and Bielik, A and Krasavin, M and Orgován, Zoltán and Domány, G and Nógrádi, K and Wágner, G and Balogh, György Tibor and Béni, Zoltán and Kóti, János and Szakács, Zoltán and Bobok, A and Kolok, S and Mikó-Bakk, ML and Vastag, Monika and Sághy, K and Laszy, J and Halász, AS and Balázs, O and Gál, K and Greiner, István and Szombathelyi, Zsolt and Keserű, György Miklós},
	doi = {10.1021/acs.jmedchem.6b01858},
	journal-iso = {J MED CHEM},
	journal = {JOURNAL OF MEDICINAL CHEMISTRY},
	volume = {60},
	unique-id = {3291825},
	issn = {0022-2623},
	year = {2017},
	eissn = {1520-4804},
	pages = {2470-2484},
	orcid-numbers = {Balogh, György Tibor/0000-0003-3347-1880; Béni, Zoltán/0000-0002-1275-4155}
}

@article{MTMT:2832195,
	title = {Catalytically distinct states captured in a crystal lattice: the substrate-bound and scavenger states of acylaminoacyl peptidase and their implications for functionality},
	url = {https://m2.mtmt.hu/api/publication/2832195},
	author = {Karancsiné Menyhárd, Dóra and Orgován, Zoltán and Szeltner, Zoltán and Szamosi, Ildikó and Harmat, Veronika},
	doi = {10.1107/S1399004714026819},
	journal-iso = {ACTA CRYSTALLOGR D},
	journal = {ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY},
	volume = {71},
	unique-id = {2832195},
	issn = {0907-4449},
	year = {2015},
	eissn = {1399-0047},
	pages = {461-472},
	orcid-numbers = {Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Harmat, Veronika/0000-0002-1866-9904}
}