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
Exploring the chemical space of orally bioavailable PROTACs
Part of Drug Discovery Today, 2024
Molecular chameleons in drug discovery
Part of Nature Reviews Chemistry, p. 45-60, 2024
Simulation Reveals the Chameleonic Behavior of Macrocycles
Part of Journal of Chemical Information and Modeling, p. 138-146, 2023
Predictive Modeling of PROTAC Cell Permeability with Machine Learning
Part of ACS Omega, p. 5901-5916, 2023
Going Viral: An Investigation into the Chameleonic Behaviour of Antiviral Compounds
Part of Chemistry - A European Journal, 2023
Macrocycles in Drug Discovery?Learning from the Past for the Future
Part of Journal of Medicinal Chemistry, p. 5377-5396, 2023
Part of Arthritis & Rheumatology, p. 1110-1119, 2023
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
Conformational Sampling Deciphers the Chameleonic Properties of a VHL-Based Degrader
Part of Pharmaceutics, 2023
Part of Proceedings of the National Academy of Sciences of the United States of America, 2023
Structure-based virtual screening discovers potent and selective adenosine A1 receptor antagonists
Part of European Journal of Medicinal Chemistry, 2023
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
- Download full text (pdf) of 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
Linker-Dependent Folding Rationalizes PROTAC Cell Permeability br
Part of Journal of Medicinal Chemistry, p. 13029-13040, 2022
Enhancing preclinical drug discovery with artificial intelligence
Part of Drug Discovery Today, p. 967-984, 2022
Part of Journal of the American Chemical Society, p. 2905-2920, 2022
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
- Download full text (pdf) of Importance of Binding Site Hydration and Flexibility Revealed When Optimizing a Macrocyclic Inhibitor of the Keap1-Nrf2 Protein-Protein Interaction
Mining Natural Products for Macrocycles to Drug Difficult Targets
Part of Journal of Medicinal Chemistry, p. 1054-1072, 2021
Structure-Guided Design of G-Protein-Coupled Receptor Polypharmacology
Part of Angewandte Chemie International Edition, p. 18022-18030, 2021
Fragment-based design of selective GPCR ligands guided by free energy simulations
Part of Chemical Communications, p. 12305-12308, 2021
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
- Download full text (pdf) of Employing complementary spectroscopies to study the conformations of an epimeric pair of side-chain stapled peptides in aqueous solution
Solution Conformations Shed Light on PROTAC Cell Permeability
Part of ACS Medicinal Chemistry Letters, p. 107-114, 2021
Cell Permeability of Isomeric Macrocycles: Predictions and NMR Studies
Part of ACS Medicinal Chemistry Letters, p. 983-990, 2021
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
Solubility prediction in the bRo5 chemical space: where are we right now?
Part of ADMET and DMPK, p. 207-214, 2020
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
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
Part of ACS Omega, p. 22245-22250, 2019
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
Part of Organic Letters, p. 5737-5742, 2018
T cells specific for post-translational modifications escape intrathymic tolerance induction
Part of Nature Communications, 2018
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