Kihlberg Group

Chemical tools for research and drug discovery beyond traditional drug space
Scientific developments during the last decades have created unparalleled opportunities to unravel disease mechanisms and to discover drugs. Unfortunately, many novel targets have binding sites that cannot be modulated with small, drug-like molecules. Instead, compounds with different chemical properties are required, but they must still combine potency and selectivity with cellular permeability that allow them to reach their targets. Our research concerns discovery of such novel, but challenging chemical probes that have potential for development into drugs.
The research is performed at the interface between chemical biology and biomedicine. Our projects focus on how chemical probes for difficult targets should be designed and this insight is then applied to the discovery of probes that are used to elucidate molecular signaling in cancer, chronic kidney disease and rheumatoid arthritis.
Group members
Publications
A membrane permeability database for nonpeptidic macrocycles
Part of Scientific Data, 2025
- DOI for A membrane permeability database for nonpeptidic macrocycles
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Part of ACS Medicinal Chemistry Letters, p. 681-687, 2025
- DOI for Linker-Determined Folding and Hydrophobic Interactions Explain a Major Difference in PROTAC Cell Permeability
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Structure-based discovery of positive allosteric modulators of the A1 adenosine receptor
Part of Proceedings of the National Academy of Sciences of the United States of America, 2025
- DOI for Structure-based discovery of positive allosteric modulators of the A1 adenosine receptor
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Part of Molecular Therapy, p. 3528-3545, 2025
- DOI for Tolerogenic antigen-specific vaccine induces VISTA-enriched regulatory T cells and protects against arthritis in DRB1*04:01 mice
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Autoantibodies to joint-related peptides as predictive markers in early rheumatoid arthritis
Part of Rheumatology, p. 2227-2232, 2025
- DOI for Autoantibodies to joint-related peptides as predictive markers in early rheumatoid arthritis
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Virtual Fragment Screening for DNA Repair Inhibitors in Vast Chemical Space
Part of Nature Communications, 2025
- DOI for Virtual Fragment Screening for DNA Repair Inhibitors in Vast Chemical Space
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Exploring the chemical space of orally bioavailable PROTACs
Part of Drug Discovery Today, 2024
- DOI for Exploring the chemical space of orally bioavailable PROTACs
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Discovery of a Series of Macrocycles as Potent Inhibitors of Leishmania Infantum
Part of Journal of Medicinal Chemistry, p. 18170-18193, 2024
- DOI for Discovery of a Series of Macrocycles as Potent Inhibitors of Leishmania Infantum
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Beware of extreme calculated lipophilicity when designing cyclic peptides
Part of Nature Chemical Biology, p. 1242-1245, 2024
Molecular chameleons in drug discovery
Part of Nature Reviews Chemistry, p. 45-60, 2024
Impact of Linker Composition on VHL PROTAC Cell Permeability
Part of Journal of Medicinal Chemistry, p. 638-657, 2024
- DOI for Impact of Linker Composition on VHL PROTAC Cell Permeability
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Simulation Reveals the Chameleonic Behavior of Macrocycles
Part of Journal of Chemical Information and Modeling, p. 138-146, 2023
- DOI for Simulation Reveals the Chameleonic Behavior of Macrocycles
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Predictive Modeling of PROTAC Cell Permeability with Machine Learning
Part of ACS Omega, p. 5901-5916, 2023
- DOI for Predictive Modeling of PROTAC Cell Permeability with Machine Learning
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Going Viral: An Investigation into the Chameleonic Behaviour of Antiviral Compounds
Part of Chemistry - A European Journal, 2023
- DOI for Going Viral: An Investigation into the Chameleonic Behaviour of Antiviral Compounds
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Macrocycles in Drug Discovery?Learning from the Past for the Future
Part of Journal of Medicinal Chemistry, p. 5377-5396, 2023
- DOI for Macrocycles in Drug Discovery?Learning from the Past for the Future
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Design of Drug Efficacy Guided by Free Energy Simulations of the β2-Adrenoceptor
Part of Angewandte Chemie International Edition, 2023
- DOI for Design of Drug Efficacy Guided by Free Energy Simulations of the β2-Adrenoceptor
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Structure-based virtual screening discovers potent and selective adenosine A1 receptor antagonists
Part of European Journal of Medicinal Chemistry, 2023
- DOI for Structure-based virtual screening discovers potent and selective adenosine A1 receptor antagonists
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Part of Journal of Experimental Medicine, 2023
Part of Arthritis & Rheumatology, p. 1110-1119, 2023
- DOI for Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis
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Part of Proceedings of the National Academy of Sciences of the United States of America, 2023
Conformational Sampling Deciphers the Chameleonic Properties of a VHL-Based Degrader
Part of Pharmaceutics, 2023
- DOI for Conformational Sampling Deciphers the Chameleonic Properties of a VHL-Based Degrader
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PROTAC cell permeability and oral bioavailability: a journey into uncharted territory
Part of Future Medicinal Chemistry, p. 123-126, 2022
Part of Annals of the Rheumatic Diseases, p. 480-489, 2022
- DOI for Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide and the T-cell receptor
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Enhancing preclinical drug discovery with artificial intelligence
Part of Drug Discovery Today, p. 967-984, 2022
- DOI for Enhancing preclinical drug discovery with artificial intelligence
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Part of Journal of the American Chemical Society, p. 2905-2920, 2022
- DOI for Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses
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Part of Journal of Medicinal Chemistry, p. 3473-3517, 2022
- DOI for Importance of Binding Site Hydration and Flexibility Revealed When Optimizing a Macrocyclic Inhibitor of the Keap1-Nrf2 Protein-Protein Interaction
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Linker-Dependent Folding Rationalizes PROTAC Cell Permeability
Part of Journal of Medicinal Chemistry, p. 13029-13040, 2022
- DOI for Linker-Dependent Folding Rationalizes PROTAC Cell Permeability
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Mining Natural Products for Macrocycles to Drug Difficult Targets
Part of Journal of Medicinal Chemistry, p. 1054-1072, 2021
- DOI for Mining Natural Products for Macrocycles to Drug Difficult Targets
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Structure-Guided Design of G-Protein-Coupled Receptor Polypharmacology
Part of Angewandte Chemie International Edition, p. 18022-18030, 2021
- DOI for Structure-Guided Design of G-Protein-Coupled Receptor Polypharmacology
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Fragment-based design of selective GPCR ligands guided by free energy simulations
Part of Chemical Communications, p. 12305-12308, 2021
- DOI for Fragment-based design of selective GPCR ligands guided by free energy simulations
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Part of RSC Advances, p. 4200-4208, 2021
- DOI for Employing complementary spectroscopies to study the conformations of an epimeric pair of side-chain stapled peptides in aqueous solution
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Solution Conformations Shed Light on PROTAC Cell Permeability
Part of ACS Medicinal Chemistry Letters, p. 107-114, 2021
- DOI for Solution Conformations Shed Light on PROTAC Cell Permeability
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Cell Permeability of Isomeric Macrocycles: Predictions and NMR Studies
Part of ACS Medicinal Chemistry Letters, p. 983-990, 2021
- DOI for Cell Permeability of Isomeric Macrocycles: Predictions and NMR Studies
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Part of ACS Medicinal Chemistry Letters, p. 13-23, 2021
Is GPR146 really the receptor for proinsulin C-peptide?
Part of Bioorganic & Medicinal Chemistry Letters, 2020
- DOI for Is GPR146 really the receptor for proinsulin C-peptide?
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Part of Journal of Pharmaceutical Sciences, p. 301-313, 2020
Solution Conformations Explain the Chameleonic Behaviour of Macrocyclic Drugs
Part of Chemistry - A European Journal, p. 5231-5244, 2020
Docking Finds GPCR Ligands in Dark Chemical Matter
Part of Journal of Medicinal Chemistry, p. 613-620, 2020
Solubility prediction in the bRo5 chemical space: where are we right now?
Part of ADMET and DMPK, p. 207-214, 2020
- DOI for Solubility prediction in the bRo5 chemical space: where are we right now?
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Drug Syntheses Beyond the Rule of 5
Part of Chemistry - A European Journal, p. 49-88, 2020
Macrocyclic Peptides Uncover a Novel Binding Mode for Reversible Inhibitors of LSD1
Part of ACS Omega, p. 3979-3995, 2020
- DOI for Macrocyclic Peptides Uncover a Novel Binding Mode for Reversible Inhibitors of LSD1
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Part of Journal of Organic Chemistry, p. 6982-6991, 2019
Intramolecular hydrogen bonding: An opportunity for improved design in medicinal chemistry
Part of Medicinal research reviews (Print), p. 1707-1729, 2019
Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging
Part of Analytical and Bioanalytical Chemistry, p. 2809-2816, 2019
- DOI for Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging
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Part of ACS Omega, p. 22245-22250, 2019
- DOI for Conformation of the Macrocyclic Drug Lorlatinib in Polar and Nonpolar Environments: A MD Simulation and NMR Study
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Integrative approaches in HIV-1 non-nucleoside reverse transcriptase inhibitor design
Part of WIREs Comput Mol Sci, 2018
Part of Journal of Medicinal Chemistry, p. 4189-4202, 2018
The Solvent Polarity Dependence of Macrocycles’ Conformations
2018
Conformational Analysis of Rifampicin in Solution
2018
Conformational Analysis of Rifampicin in Solution.
2018