Konrad F. Koehler
Thyroid hormone receptorBiological activityLigand (biochemistry)Thyroid hormone receptor betaGABAA receptorReceptorChemistrySteric effectsAntagonist1,3-Dipolar cycloadditionBenzodiazepineAgonistNitroneCycloadditionBiochemistryPharmacophoreRegioselectivityStereochemistryLigandInverse agonist
Publications 37
#1Weijiang ZhangH-Index: 7
#2Konrad F. KoehlerH-Index: 21
Last. James M. CookH-Index: 47
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The nuclear hormone receptor retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) is a promising target for the treatment of autoimmune diseases. A small molecule, inverse agonist of the receptor is anticipated to reduce production of IL-17, a key proinflammatory cytokine. Through a high-throughput screening approach, we identified a molecule displaying promising binding affinity for RORC2, inhibition of IL-17 production in Th17 cells, and selectivity against the related RORA an...
7 CitationsSource
#1Stefan Nilsson (KI: Karolinska Institutet)H-Index: 26
#2Konrad F. Koehler (Novum)H-Index: 21
Last. Jan-Ake Gustafsson (KI: Karolinska Institutet)H-Index: 148
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Classical selective oestrogen receptor modulators are well established in the treatment of breast cancer and osteoporosis, but emerging knowledge on the oestrogen receptor subtypes α and β suggests that subtype-selective modulators may hold promise for more efficacious and safer treatments of many other diseases and symptoms.
176 CitationsSource
#1Konrad F. Koehler (Novum)H-Index: 21
#2Sandra GordonH-Index: 3
Last. Johan MalmH-Index: 14
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A new high-affinity thyroid hormone antagonist 6 with druglike properties was designed and synthesized. The compound behaved as an antagonist in a cell transactivation assay, and in a first in vivo experiment in rats.
25 CitationsSource
#1Elena Lo PiparoH-Index: 10
#2Konrad F. KoehlerH-Index: 21
Last. Emilio BenfenatiH-Index: 36
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The overall goal of this study has been to validate computational models for predicting aryl hydrocarbon receptor (AhR) binding. Due to the unavailability of the AhR X-ray crystal structure we have decided to use QSARs models for the binding prediction virtual screening. We have built up CoMFA, Volsurf, and HQSAR models using as a training set 84 AhR ligands. Additionally, we have built a hybrid model combining two of the final selected models in order to give a single operational system. The re...
27 CitationsSource
#1Ana-Maria Garcia Collazo (Novum)H-Index: 1
#2Konrad F. Koehler (Novum)H-Index: 21
Last. Johan Malm (Novum)H-Index: 14
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Abstract Based on the examination of the crystal structure of rat TRβ complexed with 3,5,3′-triiodo- l -thyronine ( 2 ) a novel TRβ-selective indole derivative 6b was prepared and tested in vitro. This compound was found to be 14 times selective for TRβ over TRα in binding and its β-selectivity could be rationalized through the comparison of the X-ray crystallographic structures of 6b complexed with TRα and TRβ.
19 CitationsSource
#1Yi-Lin Li (Novum)H-Index: 4
#2Chris Litten (Novum)H-Index: 4
Last. Johan Malm (Novum)H-Index: 14
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Abstract Based on the examination of the X-ray crystallographic structures of the LBD of TRα and TRβ in complex with KB-141 ( 2 ), a number of novel 4′-hydroxy bioisosteric thyromimetics were prepared. Optimal affinity and β-selectivity (33 times), was found with a medium-sized alkyl-substituted amido group; iso -butyl ( 12c ). It can be concluded that bioisosteric replacements of the 4′-hydroxy position represent a new promising class of TRβ-selective synthetic thyromimetics.
20 CitationsSource
#1Chunyan Zhao (KI: Karolinska Institutet)H-Index: 28
#2Gudrun Toresson (KI: Karolinska Institutet)H-Index: 12
Last. Karin Dahlman-Wright (KI: Karolinska Institutet)H-Index: 45
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Estrogens exert their physiological effects through two estrogen receptor (ER) subtypes, ER R and ER‚. In mouse, the cloning of an alternative splice variant of the wild-type ER ‚ (mER‚1), mER‚2, which contains an 18 amino acid insertion in the ligand binding domain, contributed an additional level of complexity to estrogen signaling. In this study we have assayed the interaction of several known ligands with mER‚1 and mER‚2. The binding affinity of estradiol was 14-fold higher for mER‚1 than fo...
24 CitationsSource
#1Asa Hedfors (Novum)H-Index: 1
#2Theresa AppelqvistH-Index: 1
Last. Johan MalmH-Index: 14
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Based on the recently described concept of indirect antagonism of nuclear receptors, a series of thyroid hormone receptor (TR) antagonists were prepared, in which the outer ring of a thyromimetic was replaced with alkyl chains of variable length and branch. The results of a binding assay for the human TR and reporter cell assay revealed, within this series, a positive correlation between increasing bulk of the alkyl group and affinity to TRs. Compared with already reported TR antagonists, their ...
24 CitationsSource
#1Marcus C. RudaH-Index: 2
#2Nina KannH-Index: 19
Last. Konrad F. KoehlerH-Index: 21
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A library of 6-phenylquinolin-2(1H)-ones with diversity at position I and the ortho, meta, and para positions of the pendant phenyl ring has been synthesized using solid-phase parallel synthetic techniques. A key step in the synthesis of the library is a tandem alkylation cleavage in which diversity can be introduced at position 1 simultaneously to the cleavage from the resin. The yields of this step were significantly improved over what has previously been reported by addition of cesium carbona...
4 CitationsSource
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