Kihlberg Group
![Illustration of cell membrane and drug molecule.](/images/200.1407e4018ecb8d53152a290/1713363499910/Kihlberg_startsida_1932px.jpg)
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.
Publications
Exploring the chemical space of orally bioavailable PROTACs
Part of Drug Discovery Today, 2024
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Molecular chameleons in drug discovery
Part of Nature Reviews Chemistry, p. 45-60, 2024
Conformational Sampling Deciphers the Chameleonic Properties of a VHL-Based Degrader
Part of Pharmaceutics, 2023
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Simulation Reveals the Chameleonic Behavior of Macrocycles
Part of Journal of Chemical Information and Modeling, p. 138-146, 2023
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Predictive Modeling of PROTAC Cell Permeability with Machine Learning
Part of ACS Omega, p. 5901-5916, 2023
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Going Viral: An Investigation into the Chameleonic Behaviour of Antiviral Compounds
Part of Chemistry - A European Journal, 2023
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Structure-based virtual screening discovers potent and selective adenosine A1 receptor antagonists
Part of European Journal of Medicinal Chemistry, 2023
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Part of Proceedings of the National Academy of Sciences of the United States of America, 2023
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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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 Journal of Experimental Medicine, 2023
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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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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Linker-Dependent Folding Rationalizes PROTAC Cell Permeability br
Part of Journal of Medicinal Chemistry, p. 13029-13040, 2022
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Enhancing preclinical drug discovery with artificial intelligence
Part of Drug Discovery Today, p. 967-984, 2022
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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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Solution Conformations Shed Light on PROTAC Cell Permeability
Part of ACS Medicinal Chemistry Letters, p. 107-114, 2021
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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
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
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Fragment-based design of selective GPCR ligands guided by free energy simulations
Part of Chemical Communications, p. 12305-12308, 2021
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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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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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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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Part of Journal of Pharmaceutical Sciences, p. 301-313, 2020
Drug Syntheses Beyond the Rule of 5
Part of Chemistry - A European Journal, p. 49-88, 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
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
Conformational Analysis of Rifampicin in Solution
2018
Part of Synlett, p. 1187-1190, 2018
Opportunities and guidelines for discovery of orally absorbed drugs in beyond rule of 5 space
Part of Current Opinion in Chemical Biology, p. 23-29, 2018
Cyclophilin Succumbs to a Macrocyclic Chameleon
Part of Journal of Medicinal Chemistry, p. 9469-9472, 2018
Part of ACS Omega, p. 11742-11757, 2018
- DOI for Conformational Sampling of Macrocyclic Drugs in Different Environments: Can We Find the Relevant Conformations?
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Part of Organic Letters, p. 5737-5742, 2018
T cells specific for post-translational modifications escape intrathymic tolerance induction
Part of Nature Communications, 2018
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Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis
Part of Journal of Medicinal Chemistry, p. 4774-4790, 2018
Part of Frontiers in Immunology, 2018
- DOI for A Shared Epitope of Collagen Type XI and Type II Is Recognized by Pathogenic Antibodies in Mice and Human with Arthritis
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