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In Young Lee

Publications and source records attributed to In Young Lee.

5 recordsLinked to original sources
PubMed2004

Pyrazolo[1,5-a]pyrimidines: estrogen receptor ligands possessing estrogen receptor beta antagonist activity.

In our search for novel subtype-selective estrogen receptor (ER) ligands, we have examined various heterocyclic units as core structural elements. Here, we have investigated the fused, bicyclic pyrazolo[1,5-a]pyrimidine core, which is a system that allows for analogues to be readily assembled in a library-like fashion. This series of pyrazolo[1,5-a]pyrimidine ER ligands provided us with a new pharmacological profile for an ER ligand: compounds that are passive on both ERs, with a distinct potency selectivity in favor of ERbeta. The most distinctive ligand in this series, 2-phenyl-3-(4-hydroxyphenyl)-5,7-bis(trifluoromethyl)-pyrazolo[1,5-a]pyrimidine, was 36-fold selective for ERbeta in binding. Curiously, on the basis of molecular modeling, the ERbeta binding selectivity of compounds in this series appears to be derived from differing orientations that they adapt in the ligand binding pockets of ERalpha vs ERbeta. In transcription assays this pyrazolopyrimidine was fully effective as an ERbeta antagonist while exhibiting no significant activity on ERalpha. Thus, this ligand functions as a potency- and efficacy-selective ERbeta antagonist that would abrogate estrogen action through ERbeta with minimal effects on its activity through ERalpha; as such, it could be used to study the biological function of ERbeta.

Binding, Competitive↗
PubMed2004

Estrogen receptor microarrays: subtype-selective ligand binding.

We present the first example of a nuclear hormone receptor microarray, using for illustration the ligand-binding domains of the two estrogen receptors, ERalpha-LBD and ERbeta-LBD. The proteins are printed and allowed to attach to aldehyde slides; the efficiency of attachment depends on whether the LBD is liganded with agonists (low attachment) versus liganded with antagonists or unliganded (high attachment). This suggests that attachment is orientation specific and involves principally a single lysine residue. The attached ERs retain good ligand-binding activity that can be assessed using an estradiol-fluorophore conjugate, and specific and ER subtype-selective binding of ligands can be determined conveniently in competitive binding assays. This powerful new, high-throughput technique to study ligand binding to ER-LBDs can be extended to other nuclear hormone receptors and adapted to assay the recruitment of coregulator proteins.

Aldehydes↗
PubMed2003

QSAR studies on piperazinylalkylisoxazole analogues selectively acting on dopamine D3 receptor by HQSAR and CoMFA.

QSAR studies for piperazinylalkylisoxazole analogues were conducted by hologram QSAR (HQSAR) and comparative molecular field analysis (CoMFA) to explain the binding affinities of 264 ligands acting on dopamine D(3) receptor. The HQSAR was assessed by r(2) value of 0.917 and cross validated q(2) value of 0.841. In the CoMFA, r(2) is 0.919 and cross validated q(2) is 0.727. The results provide the tools for predicting the affinity of related compounds and guiding the design of new ligands.

Chemical Phenomena↗
PubMed2002

Low-flow, long-term air sampling under normal domestic activity to measure house dust mite and cockroach allergens.

Successful applications of air sampling for the quantification of exposure to indoor allergens have been reported, but its efficiency is still controversial. We evaluated whether the low-flow, long-term air sampling in normal domestic activity conditions can quantify the exposure of house dust mites (HDM) and cockroaches (CR) allergens or not. Airborne Der f 1 and Bla g 1 were captured with a personal air sampler in 25 bedrooms during normal domestic activity. Quantification of the major allergens in the reservoir dust and the extraction of the air sampler filters were done with two-site ELISA kits. Airborne Der f 1 was measured above the threshold level of detection in 15 houses (60%). Detection rate of airborne Der f 1 was significantly higher in those houses where D. farinae was microscopically found in the reservoir dusts (76.5% vs. 25%, chi 2 = 6.0, p = 0.014). Airborne Der f 1 was more frequently detected in the houses with higher Der f 1 (> or = 10 micrograms/g dust) in bedding reservoir dust than the other group (91% vs. 35.7%, chi 2 = 7.819, p = 0.005), and the median value of airborne Der f 1 was also significantly higher in that group (14.0 pg/m3 vs. below detection limit, p = 0.002). Airborne Der f 1 was significantly correlated with Der f 1 in bedding reservoir dust (r = 0.591, p < 0.01). Airborne Bla g 1 was measured with ELISA in 16 houses (64%), and it was more frequently detected in the houses where the CRs were captured by adhesive traps (91% vs. 57%, chi 2 = 3,484, p = 0.06). The median concentration of Bla g 1 in the filter was also higher in the houses with captured CRs (0.12 vs. 0.05 mU/m3, p = 0.06), but the level of Bla g 1 did not correlate with that of the bedding dusts or the floor dusts of kitchen. These results suggested that airborne HDM or CR allergens could be measured by low-flow, long-term air sampling, and that it might be one of appropriate modalities for evaluating personal exposure to HDM and CR allergens.

Air Pollution, Indoor↗